International Journal of Trend in Scientific Research and Development (IJTSRD)

Volume 6 Issue 3, March-April 2022 Available Online: www.ijtsrd.com e-ISSN: 2456 – 6470

Nanosponge: Leveraging Novel Technology

Radhika Kotame, Gayatri Wagh, Ehtesham Ansari
Assistant Professor, Matoshri Institute of Pharmacy, Dhanore, Maharashtra, India

ABSTRACT How to cite this paper: Radhika Kotame

The effective system of targeted drug delivery has been a dream for a | Gayatri Wagh | Ehtesham Ansari
long time, yet it is deeply irritated by the complex chemical involved "Nanosponge: Leveraging Novel
in the development of the latest systems. The advanced drug delivery Technology"
system has a number of problems such as poor skin tone, skin Published in
International Journal
irritation, allergies and more. The biggest problems for improved
of Trend in
chemical companies are their poor melting of water and pharmacy Scientific Research
problems. These water-soluble drugs show few problems in and Development
combining them with a non-perishable variety and therefore the main (ijtsrd), ISSN: 2456- IJTSRD49469
problems associated with them are their very low bioavailability. The 6470, Volume-6 |
development of nanosponges has been a major step forward in Issue-3, April 2022, pp.836-847, URL:
overcoming these problems. Nanosponges are a novel class of www.ijtsrd.com/papers/ijtsrd49469.pdf
colloidal structures based on hyper-crosslinked polymer consisting of
solid colloidal nanoparticles and nanosized holes. These colloidal Copyright © 2022 by author (s) and
carriers with nano-size were recently developed and proposed for International Journal of Trend in
drug delivery, as their use can dissolve soluble drugs in the water and Scientific Research and Development
Journal. This is an
provide long-term release and improve drug availability by altering Open Access article
pharmacokinetic parameters of actives. . The development of distributed under the
nanosponges as drug delivery systems, with special reference to terms of the Creative Commons
cyclodextrin-based nanosponges, is presented in this article. In the Attribution License (CC BY 4.0)
current review, attempts have been made to show the characteristics (http://creativecommons.org/licenses/by/4.0)
of cyclodextrin based on nanosponges and their applications in drug
formation. The main focus is on discussing preparation methods,
character separation methods and the use of these novel drug delivery
carriers for therapeutic purposes.
KEYWORDS: Nanosponge, poorsolubility, polymers, Medical,
Formulations

INTRODUCTION
Nanosponges are a novel class of hyper-crosslinked
polymer based colloidal structures consisting of solid
colloidal nanoparticles and nanosized holes. Good-
- Known examples of nanosponge nanosponges based
on titanium (1), silicon nano-sponge particles (2),
hyper-crosslinked polystyrene nanosponges (3) and
cyclodextrin-supported nanosponges (4).
An important attraction of nanosponge technology
stems from the difficulty that has been encountered in
the general structure in extracting active ingredients
over time. Higher focus compared to shorter duration
of action are common features of skin and personal
care products. This can lead to a short-term drinking
cycle followed by prolonged neglect. Side effects
such as rashes or other serious side effects (due to the
active ingredient penetrating the skin) are a major
barrier to those skin and personal care products. Thus
another technology that overcame these barriers was
the need for an hour. In recent decades, nanoparticles
as drug delivery systems have received a lot of
attention. Nanotechnology even allows for the
continuous release of active substances, compounds
and agents, reducing irritation while maintaining
efficiency, thus making nanoparticles a flexible
vehicle for drug delivery (5, 6). However, only a few
nanopreparations, such as abraxane, have reached the
market (7). Proteins, peptides, genes, anti-cancer
agents and biomolekules are loaded into
nanoparticulate delivery systems and thoroughly
researched to reduce adverse effects and improve
efficiency (8-10). Nano particles provide a controlled
release of bound drugs and during this action provide
protection against drug particles in physical
conditions that maintain the bioactivity of the
compound. Nanoparticles can be used to make drugs
in the liver, spleen and lungs as they are easily

@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022 Page 836
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
absorbed by the macrophage system (11-15). Coats oleophilic and deliquescent material and increase the
made of nanoparticles help to overcome the reticulo- dissolution of water-soluble molecules. (24,25)
endothelial detection of nanoparticles and thus bring
the drug to various body systems such as BBB (16).
Therefore, the benefits of nano-particulate drug
delivery systems include bound drug protection,
improved performance, reduced side effects,
controlled release and drug identification.
Nanoparticles come in the form of polymeric
nanoparticles, solid lipid nanoparticles,
nanoemulsions, nanosponges, carbon nanotubes,
micellar systems, dendrimers, etc. Among these,
nanosponge (NS) looks like a three-dimensional
scaffold with a long polymer. spine. The polymer in
the solution state is made up of small molecules
called crosslinkers that act as small holding hooks to
hold different parts of the polymer together. The
result is the formation of circular particles with Fig1. Structure of Nanosponges
hydrophobic holes in which drug molecules can be
trapped (17). A single nanosponge system contains a
large number of voids connected within a fixed
structure that can hold a variety of objects. The
surface is usually porous, allowing for continuous
flow of particles without particles (18). These nano-
colloidal carriers were recently proposed for drug
delivery, as their use can dissolve soluble drugs in the
water and provide long-term release, as well as Nanosponges include a variety of Nanoparticles that
improve drug drug availability by altering incorporate drug molecules within their spinal cord
pharmacokinetic parameters of active ingredients through the process of coagulation, Nanoparticles are
(19). often divided into synthetic Nanoparticles and
synthetic Nanoparticles. The primary type is
Identifying drug delivery has long been a study represented by a nanosponge-like nanoparticles that
therapy - how to put them in the right place within the contain a few holes that carry drug molecules. Poly
body and how to control drug delivery to eliminate nanocapsules (isobutyl-cyanoacrylate) (IBCA) also
the intended drug overdose of drug delivery programs include Nanoparticles. They will attach to the drug
has been a dream for a very long time. yet however it molecules in their aquous environment. The second
is very irritated by the complex chemistry connected class consists of Nanoparticles, which bind to drugs
[20 - 23]. The development of nanosponges is a with covakent bonds [4]. Nanosponges are able to
chemical with holes integrated delivery systems are provide solutions to many problems connected to the
small circular particles with large porous surfaces. mold. Due to their small size and hollow environment
This is used for the flexible administration of they will bind the insoluble drug within the matrix
cosmetic agents on the skin where by obtaining large and improve their bioavailability. They can bind
edges such as a reduction in total volume, the drugs that do not dissolve within the matrix and
maintenance of a permanent volume in the skin and improve their bioavailability. (26) They will be
the prevention of normal absorption. These designed to direct drugs to specific areas, prevent
nanosponges are often successfully included in the drug and supermolecule deterioration and increase
program for long-term non-binding and skin care drug resistance in a highly controlled manner.
topics thus reducing the variability of drug Nanosponge is found in an efficient way of co-
absorption, toxicity and increasing patient compliance ordinating and interacting with living and non-living
by increasing the frequency intervals. things. (27)
The .nanosponge is a new layer of fabric and is Advantages of nanosponge based drug delivery
composed of tiny particles with a few wide holes in systems
the nanometer, where a type of material is usually This technology offers entrapment of ingredients
covered. These particles are able to carry each and reduces side effects;

@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022 Page 837
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
Improved stability, increased elegance and have shown a wide range of drug loading
enhanced formulation flexibility; properties (30).
Extended release with continuous action up to They are non-toxic, particles with insoluble holes
12–24 hours;
in many natural solvents and are stable at
Incorporation of immiscible liquids is possible; temperatures up to 300 ° C (31).
Improved material processing since liquids may
be converted to powders. Nanosponges as a structure are stable over a pH
range of 1 to 11 and a temperature of up to 130 °
Disadvantages C (36).
Nanosponges comprise only small molecules [28]
Rely only on uploads. They form a clear and opalescent suspension in
water and can be reconstituted by dissolving heat,
Characteristic features of nanosponges dissolving solvents, using microwaves and
Nanosponges (1 µm or less) have a flexible ultrasounds (32).
polarity of holes. Nanosponges of a certain size
and adjustable polarity can be assembled by Sabo Their 3D architecture allows for the capture,
alternating a crosslinker with a polymer transport and release of a wide variety of objects.
component (29). They can be redirected to different sites due to their
ability to connect with different working groups.
They can be para-crystalline or crystalline form, Chemical bonds enable nanosponges to bind to the
depending on the process. The crystal formation target surface. They form complex and implanted
of nanosponges plays a very important role in complexes with different drugs (22). Magnetic
their synthesis with the drug. The drug loading properties can be transferred to nanosponges (by
capacity of nanosponges depends largely on the adding magnetic particles to the reaction mixture).
degree of polishing. Para-crystalline nanosponges
Chemical used for synthesis of Nanosponges:-
Hyper cross linked Polystyrenes, Cyclodextrins and its derivatives like Methyl β-
Cyclodextrin, Alkyloxycarbonyl-Cyclodextrins, 2- Hydroxy Propyl β-
Polymers
Cyclodextrins and Copolymers like Poly (valerolactone -allylvalerolactone), Poly
(valerolactone- allylvalerolactoneoxepane-dione), Ethyl Cellulose and PVA
Apolar
Ethanol, Dimethylacetamide, Dimethyl formamide
solvents
Diphenyl Carbonate, Diarylcarbonates, Di-Isocyanates, Pyromellitic anhydride,
Cross-linkers Carbonyl-di-Imidazoles, Epichloridrine, Glutarldehyde, Carboxylic acid
dianhydrides, 2,2-bis(acrylamido) Acetic acid and Dichloromethan.

Factors influencing the formation of nanosponges carbonyldiimidazoles (19, 30, 35) and may serve as
(33) crosslinkers. - Storage carriers of water-soluble drugs
1) Polymers and crosslinkers. - The type of polymer including peptide and protein drugs (20). A list of
used can affect the formation and performance of polymers with their applications is given in Table I.
nanosponges. Effective crosslinkers convert nano-
In addition to the nature of the polymer and
cavities molecules into three-dimensional,
crosslinker, the type of solvent and solvent medium
nanoporous structures. By adjusting the crosslinking
used in the preparation process affects the formation
rate, hydrophilic or hydrophobic components that can
of nanosponges.
hold the target compounds are formed. Depending on
the nature of the crosslinkers, nano-sponge structures 2) Types of drugs and location used for
that are soluble or insoluble are formed. communication. - Drug molecules to be combined
with nanosponges must have certain characteristics in
Hydrophilic nanosponges are formed when
order to be effectively absorbed into nanosponges.
epichlorohydrin (24) is used as a crosslinker.
Molecules with a molecular weight of between 100
Hydrophilic nanosponges can change the rate of drug
and 400 Da and a ring of less than five can easily be
release, and can be used to improve drug absorption
trapped in the nanocavity of sponges. Also, these
across all biological barriers, acting as a potent drug
molecules should be less than 10 mg mL – 1
carrier even in fast-release products. Hydrophobic
dissolved in water and the melting point should be
nanosponges can be synthesized using
below 250 ° C (23). Compounds with high melting
diphenylcarbonate (4, 19, 20, 28, 29, 34) or
points do not have high fixed values when loaded
pyromellitic anhydride (32), disocyanates (31, 55),
with nanosponges. Therefore, stable complexes

@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022 Page 838
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
between drugs and nanosponges are not available
when loaded into a tree. Drug loading is also affected
if the drug has a high melting point. Low load of the
tree can be seen with compounds dissolving at high
temperatures. These low loading rates may be
calculated due to the strength of the composite
structure. The interaction between NS pits and target
compounds depends largely on the content; that is,
the hydrophilic medium will drive molecules of living
visitors into hydrophobic holes, while the organic
solvent tends to release organic molecules trapped in
nanosponges. This strong attraction between host and
visitor molecules depends on improved chemical and
physical interactions such as matching polarity, size,
hydrophobic environment and structural properties
(34).
3) Complex temperature. - The stability of the
complex depends on the temperature change.
Consistent stability and temperature rise are
associated with the opposite.In increasing
temperatures, the apparent magnitude of the constant
decrease decreases due to the reduction of drug /
nanosponge interactions (35,36). Therefore, complete
temperature control should be maintained when
preparing nanosponges.
4) Replacement qualifications. - The type, number
and position of the substitute in the polymeric
molecule affects the complex ability of nanosponges
(26). The type of replacement is important because
the b-CD output is available in a variety of different
ways to the active groups present on the surface of the
cyclodextrin output. When compiled with the help of
crosslinker, different functional groups can produce
different types of complex substances (b-CD
nanosponges, CD-carbamate nanosponges, CD-
carbonate nanosponges, etc.)
There is a direct relationship between the available
exchange rate and the link level. The higher the
number of substitutes, the greater the likelihood that
there will be a high affinity. A higher degree of
bonding will produce more perforated nanosponges
due to the increased interaction between the polymers
forming a mesh-type network.
The position of the switch depends on the production
conditions. A change in the production process will
produce elements with different physicochemical
properties due to the localization of a different
functional group in the parent combination. For
example, when produced under different conditions,
the physicochemical properties of HP-b-CD samples
with the same rate of conversion may differ due to the
possible residence of hydroxypropyl groups in
different positions in the parent CD molecule.
Material purity can therefore have a significant
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
impact on the final quality of nanosponges, indicating
the importance of the polymer transformation rate.
As mentioned above, the type of polymer determines
the type of nanosponges that can be synthesized.
Thus, based on the polymer used, different types of
nanosponges can be developed. The above factors
should be considered during the production of
nanosponges. A few well-known examples of
nanosponges are titanium-based nanosponges (1),
silicon nanosponge particles (2), hyper-crosslinked
polystyrene nanosponges (3) and cyclodextrin-based
nanosponges (4). Among the various types of
nanosponges, cyclodextrin-based nanosponges have
received extensive attention and are widely studied.
In addition, this review focuses on cyclodextrin-based
nanosponges for therapeutic use.
Classification of Nanosponge
Nanosponge is a type of Nanoparticles that binds
molecules of drugs within their nucleus. By way of
drug synthesis, Nanoparticles can be classified as
follows:
1. Ecapsulating Nanoparticles: - This type is
represented by nanosponge and nanopartilces.
Nanosponges are similar to alginate nanosponges,
which are sponges like nano particles with
multiple holes that carry drug molecules in their
aqueous root (37,38)
2. Complex Nanoparticles: - This type of
Nanoparticles pulls molecules by charging
electrostatics.
3. Conjugating Nanoparticles: - This type of
Nanoparticles binds to drugs through binding
bonds. Unlike other Nanoparticles, they are
insoluble in water and organic solvent, thin, non-
toxic and stable at high temperatures up to 300ºC.
METHODOLOGY FOR PREPARATION OF
THE NANOSPONGES:
The various methods used for the preparation of
Nanosponges are given below:
1. SOLVENT DIFFUSION METHODS.
2. ULTRASOUND ASSISTED SYNTHESIS.
3. NANOSPONGES PREPARED FROM HYPER
CROSS LINKED CYCLODEXTRIN.
4. SOLVENT METHOD.
5. LOADING OF DRUG INTO NANOSPONGE.
1. SOLVENT DIFFUSION METHODS [39-41]
A. Distribution of Quassi emulsion solvent:
The polymer is soluble in a suitable solvent (internal
phase). The drug can be added to the solution and
dispersed under ultrasonication at 35ºC. The inner
layer is poured into a polyvinyl alcohol solution in
water after 60 minutes of stirring, the mixture is
filtered. Then the prepared nanosponges will be dried
in an oven heated at 40ºC for 12 hours.
Page 839
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
B. Emulsion solvent dispersion method:
for the preparation of the aqueous phase and the
organic phase, the aqueous phase contains the
copolymer and the organic phase contains the drug
and the polymer. The Organic phase is gradually
added to the liquid phase and is stirred for 2-3 hours
at 1000rpm. Prepared nanosponge is filtered, washed,
and then dried in air at room temperature or in a
vacant oven for 40ºC for 24 hours.
2. ULTRASOUND ASSISTED SYNTHESIS[42-
43]
The polymer is mixed with a cross linker with a
balanced ratio on the flask. The flask is then placed in
a water-filled ultrasound tub and the temperature is
maintained at 90ºC. Sonicate the mixture for 5 hours.
To remove the unresponsive polymer, the product is
washed with water. Then the product is diluted with
ethanol by removing the soxhlet .Allow the product to
dry under a vacuum of 25ºC.
3. NANOSPONGES PREPARED FROM
HYPER CROSS LINKED CYCLODEXTRIN
In this process cyclodextrin reacts with cross linkers
such as di-isocianate, diaryl carbonates, carbonyl di-
imidazoles etc. The size of the sponges is controlled
according to the body, the congestion of excess
charge attached to completely different molecules.
Depending on the connector the nanosponges are
assembled in a neutral or acidic manner. The ability
of nanosponges to combine drugs with completely
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
different properties and solubility. They are
accustomed to the development of the soluble
combination of a water soluble substance mainly BCS
tree phase II [44].
4. SOLVENT METHOD
In this chemical reaction the mixture was mixed with
an acceptable solvent, especially in the solvent aprotic
solvent such as dimethylformamide,
dimethylsulfoxide. This combination would add to
the excess crosslinker value, ideally in a crosslinker /
polymer molar quantitative relation of 4 to 16. The
reaction is from a dole without temperatures ranging
from 10ºC to solvent reflux temperature, a period that
starts at 1-40 hours. , the most popular cross linkers
are carbonyl compounds (dimethyl carbonate and
carbonyl diimidazole) [28]. for sale. by filtering under
vaccum and later in the sublimate by extracting the
soxhlet for a long time with ethyl alcohol.
Commodities are dried under vaccum and ground in a
mortar to obtain a fine powder [45].
5. LOADING OF DRUG INTO NANOSPONGE
Nanosponges for drug delivery should be made in
advance to obtain a particle size of less than 500nm.
Nanosponges are suspended in water and sonicated to
prevent the formation of aggregates and then
centrifused suspension to obtain a fraction of the
mixture. The supernatant was separated and dried by
freezing of the sample [31]. The suspension of the
nanosponge binary mixture was fine and distributed
the remaining mass of the drug and ended up being
suspended under constant motion for some time to
become more complex. Once complex, the soluble
(non-soluble) drug was separated from the complex
drug by natural process. Solid crystals of
Page 840
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
nanosponges are then obtained by evaporation of
solvent or by freezing [30,31]. The crystalline
structure of nanosponges plays a very important role
in drug synthesis. Anecdotal evidence that
paracrystalline nanosponges have shown a completely
different loading capacity compared to pure
nanosponges. Drug loading is larger with pure
nanosponges and then single paracrystalline. In
nanosponges with the wrong crystal, drug loading
occurs as a mixture rather than a complex infusion
[46].
MECHANISM OF DRUG RELEASE FROM
NANOSPONGES
Since nanosponges have an open structure
(surrounding nanosponges do not have a continuous
membrane), an active element is added to the car by
an associate-type type. The integrated component is
ready to move freely from the particles into the car
until the vehicle is fully loaded and thus equates. As
soon as the product is applied to the skin, the vehicle
containing the active ingredient receives impurities
causing a disturbance within the balance. Thus, the
flow of active substances from nanosponge particles
to vehicles begins to coagulate until the vehile is
absorbed or dried. Even when the retention of
nanosponge particles on the surface of the skin i.e. the
horn layer, the removal of the active substance
persists on the skin for a long time.
CHARACTERIZATION OF NANOSPONGES:
1) Melting phase. - The impact of NSs on drug
solubility is investigated by a phase solubility process
(48). To determine the soluble components of the
phase, the excess solvent is added to the appropriate
solvents to obtain complete solutions. Fully drug
overdose is treated with various concentrations of
empty nanosponges, 1: 1, 1: 2, 1: 3, etc. As their
concentration increases, more and more trees interact
with NS. Research is done until equity is found.
Drawing episode of NS concentration vs. drug
concentration and type of structure is defined with the
help of the Higuchi and Connors subdivision (49).
Fixed fixed values give an idea of the degree of
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
interaction between nanosponges and wood. Drug
interactions with nanosponges can increase the
solubility of solvents in the water and thus the degree
of solubility. Such a study was performed with
itraconazole loaded with cyclodextrin nanosponges
prepared by Shankar et al. Therefore, nanosponges
can significantly increase the solubility of molecules
with very low water solubility such as anti-cancer
drugs, steroids and anti-inflammatory drugs (47,48).
2) Interaction with the water level. - UV spectroscopy
is used as a tool for researching the interaction of
complete solutions. Increasing concentrations of
nanosponge solutions (1– 80 ppm) are added to the
concentrated concentrate of the tree. Samples were
kept overnight to work and finally filtered solutions
were screened for lmax and absorption was measured.
Drug loading is interpreted by taking synthetic scans
at UV radiation and analyzing changes in the
maximum absorption rate in the spectra compared to
pure drug (49).
3) Porosity - Porosity research is performed to test the
quality of nanochannels and nanocavities formed.
Porosity of nanosponges is tested with a helium
pycnometer, as helium gas can penetrate into the
internal and external channels of objects. The actual
volume of the material is determined by the removal
of helium (50). Due to their hollow nature,
nanosponges show a higher smoothness compared to
the parent polymer used to build the system.
Percentage of porosity is given by equation (1).
% Porosity (E) = Bulk Volume - Actual Volume ´
100 (1)
Bulk volume
4) Average diameter and polydispersity indices of
nanosponges - This is usually determined using
particle size analysis using a dynamic light scattering
Page 841
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
system (DLS) (also known as photon correlation
spectroscopy, PCS) (51–59). With the help of the
autocorrelation function, PCS correlates the variation
in light intensity dispersed to component size (60).
PCS / DLS measures hydrodynamic diameter, that is,
it considers all subcutaneous particles to be circular.
DLS / PCS provides particle size by taking into
account the effective viscosity, temperature and
refractive index of the dispersing medium. Therefore,
the measured particle size will be the parameter
obtained after considering all the factors. It is always
preferred to have quality results as well. Particle
quality analysis can be performed by scanning
electron microscopy (SEM), transmission electron
microscopy (TEM) or natural electron microscopy
scanning (ESEM) sample analysis. Particle size and
shape can be determined by dissolving the sample in
water or other suitable solvents and further testing
using techniques such as SEM / TEM / ESEM. For
example, paclitaxel-loaded nanosponges were
detected showing a distribution of mononodal
particles of 350 ± 25 nm, with a small distribution
(polydispersity index, p <0.2) (51).
5) Zeta Power - The Zeta strength of any system
under investigation is a measure of local billing. Extra
charging is a parameter that affects body distribution
and interaction with the biological environment. Zeta-
strength ratio includes consideration of electrical
potential, i.e., diffusion coefficient and
electrophoretic mobility (61). These values are
converted to zeta power after calculations from the
Smolu-chowski or Stokes equation calculations. PH
and electrolyte concentration (62, 63) need to be
considered when measuring zeta power. The stability
of synthetic nanopa- ticles can be measured by the
possible testing of zeta. Zeta power in water should
be ± 30 mV, high enough to provide a stable nano
suspension that does not mix over time. Cavalli et al.
measure electrophoretic flow as well zeta power
using 90 PLUS steel. To obtain zeta power, samples
of nanosponge dispersions were diluted with KCl
solution (0.1 mmol L – 1) and placed in an
electrophoretic cell, where an electrical field of about
15 V / cm (52) was used.
6) SEM and TEM. - These tools are used to test
particle size and size as described above (4) and to
obtain morphological information related to the drug
delivery system under investigation (64-72). SEM
involves the transfer of flexibility in particles formed
under a vacuum by a concentrated electron beam.
Whenever wet samples are to be investigated, ESEM
may be hired. TEM involves investigating the
morphology of fixed particles in a liquid. TEM and
SEM studies conducted by Ansari et al. prepared
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
nanosponges. A TEM study conducted by these
authors (53) revealed a typical circular shape and size
of NS. The shape and size of the developed nano-
sponges remained unaffected even after drug injection
into the nanosponges.
7) Trans-infrared (FT-IR) spectroscopy. - It serves as
a great tool for determining the existence of working
groups. After polymer synthesis, the appearance of
active clusters in the FT-IR spectrum is an indication
of the formation of bonds between the two monomer
units of the polymer. In the FTIR crystal structure,
vibration spectrum is obtained (54). The FT-IR
spectra of dried nanosponges, pure drugs and drug-
laden nanosponges are taken to understand
interactions. The spectra is found in the wavenumber
range of 4000 to 650 cm-1. FT-IR also helps in
determining the hydrophobic and hydrophilic
components in the advanced system. Ansari et al. (35)
performed a FTIR spectra comparison of resveratrol
and complex and showed significant changes in the
region of fingerprints, i.e., 900 to 1400 cm-1 showing
drug loading on nanosponges.
8) Differential scanning calorimetry (DSC) - Thermo-
analytical methods determine whether a drug object
undergoes a certain change before the temperature
drop of the improved delivery system. Changes in a
substance may be in the form of melting, evaporation,
decomposition, oxidation or polymorphic
modification showing complex formation. The
thermogram obtained by DTA and DSC can be
monitored to expand, relocate and detect new peaks
or the disappearance of certain peaks. The absence of
a high melting point of the crystalline structure drug
in the DSC thermogram is a sign of a dispersed
molecule within the polymer. Changes in weight loss
can also provide supporting evidence
Applications of nanosponges in pharmaceuticals
1) Development of drug stability- b-CD units bonded
with polymer, where the number of b-CD units bound
to the same polymer series. Several b-CD units
increase the stability of the drug complex (64-66). In
addition, the polymer may interact with b-CD
components in strengthening structures. Such studies
have been developed for proteins and peptides due to
their insufficiency, high production capacity, immune
system and immune response and poor bioavailability
and sensitivity to protease (4). Bovine serum albumin
(BSA) soluble proteins are unstable, stored in a
lyophilized state. However, proteins can be mutated
at random in lyophilization and take on a completely
different fusion in the native structure. A major factor
in the formation and development of proteins is the
need to maintain their natural composition during
processing and long-term storage. In the nanosponge-
Page 842
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
based system, BSA-like proteins are well
incorporated into swellable cyclodextrin based poly
(amidoamine) and nano sponges and increase their
stability (67).
2) Nanosponges as carriers of biocatalysts in the
delivery and release of enzymes, proteins, vaccines
and antibodies. - Proteins, peptides, enzymes and
their derivatives are used in the biomedical and
therapeutic field. Proteolytic enzymes are used to
treat cancer or a type of mucopolysaccharidosis,
while DNA and oligonucleotides are used in gene
therapy. The administration of these molecules
presents various problems and limitations (79).
Similar to protein protection and fitness concerns,
there are concerns about the enzyme, the vaccine and
the stability of the immune system. Proteins and other
macromolecules can be transported and transported
throughout the biological barrier, targeted at the site
by advertising or incorporating them into cyclodextrin
nanosponges.
3) Changing drug release. - Regular management is
an important part of many common, available service
delivery programs. However, the drug loaded on the
nanosponge structure can be stored and released
slowly over time. Hydrophilic CD NS can change the
rate of drug release, which can be used to improve
drug absorption across all biological barriers, acting
as a potent drug carrier in the formation of rapid
release. Hydrophobic CD NS may serve as a
continuous carrier of water-soluble drugs, including
peptide and protein-containing drugs (23).
Nanosponges can also be used as carriers of drugs
such as doxorubicin (an anti-cancer drug), and may
protect the drug in the stomach. The drug is released
very slowly at pH 1.1, and release is faster when the
pH is raised to 7.4.
4) Successful delivery carriers. - Cyclodextrin
nanosponges have been used as antitumor drugs such
as paclitaxel, camptothecin and tamoxifen which
present bioavailability problems because their
solubility in water is low or nonexistent. The drugs
were incorporated into nanosponges and experiments
were performed on various cell lines to investigate
their anti-inflammatory effect. Complications have
shown a greater effect than that of the drug alone
(19). The total bioavailability of paclitaxel increased
after its loading on nanosponges and was found to be
2.5 times higher than in the empty drug (34).
Econazole nitrate, an antifungal agent used topically
to relieve symptoms of candidasis, dermatophytosis,
versicolor and skin diseases, is available in creams,
ointments, ointments and solutions. The incorporation
of adsorption is not important when econazole nitrate
is applied to the skin and therefore a high
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
concentration of active agents is required for effective
treatment. To overcome this problem, econazole
nitrate nanosponges are synthesized in the form of an
emulsion solvent and are loaded with hydrogels to
form a local depot for continuous drug extraction
(68,69).
5) Development of melting. - The presence of
connecting holes and cyclodextrin in the structure
tends to interact with active molecules. These
elements cause a number of substances to be absorbed
and dissolved in the built-up holes. Blending
compounds or solid dispersion with CDs can improve
drug solubility or the rate of dissolution of drugs that
do not dissolve in water due to the reduction of drug
crystals. The effect obscures most of the hydrophobic
activity in the inner surface of the CD while the
hydrophilic hydroxyl groups in the outer surface are
always exposed to the surface; the complete effect is
that a melt-based melt is formed (82). Among the
various CDs available for sale, methylated CDs with
the lowest molar substitution are the most potent
solvents. CD nanosponges can greatly improve drug
elimination even when they are not complicated. CD
nanosponges may act as release enhancements; for
example, b-CDs have been reported to improve the
release rate of soluble drugs such as naproxen and
ketoprofen (70).
CDs also increase hydrophobic drug penetration by
increasing drug solubility and dissolution and thus
making them available at the top of the biological
barrier, where they break down into membranes
without interfering with the lipid barriers of the
barrier. The effect of CD nanosponges on drug-
soluble dexa-methasone, flurbiprofen and
doxorubicin hydrochloride, which have different
properties and solubilities was investigated by Trotta
et al. Dexamethasone and flurbiprofen are lipophilic
drugs with P logs 1.9 and 4.1, respectively, while
doxorubicin hydro-chloride is a hydrophilic drug with
a P value of 0.25. The improved aqueous solubility of
lipophilic drugs was compared with the hydrophilic
drug doxorubicin after the drugs were loaded into
nanosponges. This behavior may be attributed to the
higher number of lipophilic sites available for
lipophilic drug combinations compared to the
hydrophilic sites on cyclodextrin. Marketed
Formulations:
CONCLUSION:-
In addition to the points, it will be concluded that
Nanosponges have a wide range of useful properties,
can use a promising drug delivery tool economically,
and may be considered a brand new carrier for skin
delivery drugs and medical features. They provide a
combination of individual lipotropic and deliquescent
Page 843
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
drugs, as well as regulated patents in addition to the
drug binding in the targeted area. Theeby increases
bioavailability and performance. The level of particle
size and the degree of non-corrosion required may be
achieved by a combination of strong chemicals to
exceed the bond size. In addition, Nanosponges are
based primarily on the delivery system and protect the
active moiety from damage. The small size and round
shape of the delivery system allows for the formation
of completely different value forms such as parerral,
aerosol, topical and moreover as endless oral
quantities as needed and advanced methods.
REFERANCE
[1] L. Guo, G. Gao, X. Liu and F. Liu, Preparation
and characterization of TiO2 nanosponge,
Mater. Chem. Phys. 111 (2008) 322–325;
DOI:10.1186/1556-276X-6-551.
[2] D. Farrell, S. Limaye and S. Subramanian,
Silicon Nanosponge Particles, U. S. Pat 0, 251,
561A1, 9 Nov 2006.
[3] V. Dakankov, M. Llyin, M. Tsyurupa, G.
Timofeeva and L. Dubronina, From a dissolved
poly- styrene coil to intramolecularly hyper
cross linked nanosponges, Macromolecules 29
(1998) 8398– 8403; DOI: 10.1021/ma951673i.
[4] S. Swaminathan, L. Pastero, L. Serpe, F. Trotta,
P. Vavia, D. Aquilano, M. Trotta, G. Zara and
R. Cavalli, Cyclodextrin-based nanosponges
encapsulating camptothecin: Physicochemical
char- acterization, stability and cytotoxicity,
Eur. J. Pharm. Biopharm. 74 (2010) 193–201;
DOI: 10.1016/ j.ejpb.2009.11.003.
[5] F. Melani, P. Mura, M. Adamo, F. Maestrelli,
P. Gratteri and C. Bonaccini, New docking
CFF91 parameters specific for cyclodextrin
inclusion complexes, Chem. Phys. Lett. 370
(2003) 280–292; DOI:10.1016/S0009-
2614(03)00126-X.
[6] P. Couvreur and C. Vauthier, Nanotechnology:
intelligent design to treat complex disease,
Pharm. Res. 23 (2006) 1417–1450;
DOI:10.1007/s11095-006-0284-8.
[7] C. Zhang, N. Awasthi, M. A. Schwarz, S. Hinz
and R. E. Schwarz, Superior antitumor activity
of nanoparticle albumin-bound paclitaxel in
experimental gastric cancer, PLoS One. 8
(2013) e58037;
DOI:10.1371/journal.pone.0058037.
[8] Y. Fukumori and H. Ichikawa, Nanoparticles
for cancer therapy and diagnosis, Adv. Powder
Technol. 17 (2006) 1–28;
DOI:10.1163/156855206775123494.
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
[9] M. Morishita and N. Peppas, Is the oral route
possible for peptide and protein drug delivery,
Drug Discov. Today 11 (2006) 905–910;
DOI:10.1007/s11095-006-0284-8.
[10] H. Cohen, R. Levy, J. Gao, I. Fishbein, V.
Kousaev, S. Sosnowski, S. Slomkowski and G.
Golomb, Sustained delivery and expression of
DNA encapsulated in polymeric nanoparticles,
Gene Ther. 7 (2000) 1896–1905;
DOI:10.1038/sj.gt.3301318.
[11] L. Grislain, P. Couvreur, V. Lenaerts, M.
Roland, D. Deprez-Decampeneere and P.
Speiser, Phar- macokinetics and distribution of
a biodegradable drug-carrier, Int. J. Pharm. 15
(1983) 335–345; DOI:10.1016/0378-
5173(83)90166-7.
[12] L. Illum, S. S. Davis, C. G. Wilson, N. W.
Thomas, M. Frier and J. G. Hardy, Blood
clearance and organ deposition of intravenously
administered colloidal particles, The effects of
particle size, nature and shape, Int. J. Pharm. 12
(1982) 135–146; DOI:10.1016/0378-
5173(82)90113-2.
[13] P. Couvreur, B. Kante, V. Lenaerts, V.
Scailteur, M. Roland and P. Speiser, Tissue
distribution of antitumor drugs associated with
polyalkylcyanoacrylate nanoparticles, J. Pharm.
Sci. 69 (1980) 199–202;
DOI:10.1002/jps.2600690222.
[14] J. Kreuter, Nanoparticles, in Encyclopedia of
Pharmaceutical Technology (Ed. J. Swarbrick
and J. C. Boylan), Marcel Dekker In., New
York 1994, pp. 165–190.
[15] J. Xing, D. Zhang and T. Tan, Studies on the
oridonin-loaded poly(D, L-lactic acid)
nanoparti- cles in vitro and in vivo, Int. J. Biol.
Macromol. 40 (2007) 153–158;
DOI:10.1016/j.ijbiomac.2006.07.001.
[16] E. Garcia-Garcia, K. Andrieux, S. Gil and P.
Couvreur, Colloidal carriers and blood-brain
barrier (BBB) translocation: a way to deliver
drugs to the brain, Int. J. Pharm. 298 (2005)
274–292; DOI:10.1016/j.ijpharm.2005.03.031.
[17] S. Subramanian, A. Singireddy, K.
Krishnamoorthy and M. Rajappan,
Nanosponges: A Novel Class of Drug Delivery
System – Review, J. Pharm. Pharmac. Sci. 15
(2012) 103–111.
[18] A. Nokhodchi, M. Jelvehgari, M. Reza Siahi
and M. Reza Mozafar, Factors affecting the
mor- phology of benzoyl peroxide
microsponges, Micron 38 (2007) 834–840,
DOI: 10.1016/j.micron.2007.06.012.
Page 844
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
[19] F. Trotta and R. Cavalli, Characterization and
application of new hyper-cross-linked cyclo-
dextrins, Compos. Interfaces 16 (2009) 39–48,
DOI: 10.1163/156855408X379388.
[20] F. Trotta, R. Cavalli, V. Tumiatti, O. Zerbinati,
C. Roggero and R. Vallero, Ultrasound
Assisted Synthesis of Cyclodextrin Based
Nanosponges, EP Pat 1786841A1, 23May,
2007.
[21] S. Eki, T. Lei, L. Jingquan, J. Zhongfan, B.
Cyrille and P. D. Thomas, Biodegradable star
poly- mers functionalized with b-cyclodextrin
inclusion complexes, Biomacromolecules, 10
(2009) 2699– 2707; DOI:10.1021/bm900646g.
[22] S. Swaminathan, R. Cavalli, F. Trotta, P.
Ferruti, E. Ranucci, I. Gerges, A. Manfredi, D.
Marinotto and P. Vavia, In vitro release
modulation and conformational stabilization of
a model protein using swellable
polyamidoamine nanosponges of b-
cyclodextrin, J. Incl. Phenom. Macrocycl.
Chem. 68 (2010) 183–191;
DOI:10.1007/s10847-010-9765-9.
[23] A. Vyas, S. Saraf and S. Saraf, Cyclodextrin
based novel drug delivery systems, J. Incl.
Phenom. Macrocycl. Chem. 62 (2008) 23–42;
DOI: 10. 1007/s10847-008-9456-y.
[24] T. Girek and W. Ciesielski, Polymerization of
b-cyclodextrin with maleic anhydride along
with thermogravimetric study of polymers, J.
Incl. Phenom. Macrocycl. Chem. (2010) 1–7;
DOI: 10.1007/s10847-010-9778-4.
[25] D. Li and M. Ma, Nanosponges: From
inclusion chemistry to water purifying
technology, Chem. Sci. Technol. (1999) 26–28.
[26] C. Rajeswari, A. Alka, A. Javed and R. Khar,
Cyclodextrins in drug delivery: an update
review, AAPS PharmSciTech. 6 (2005) E329-
E357; DOI: 10.1208/pt060243.
[27] A. Modi and P. Tayade, Comparative solubility
enhancement profile of valdecoxib with differ-
ent solubilization approaches, Ind. J. Pharm.
Sci. 69 (2007) 427–430; DOI:10.4103/0250-
474X.33156.
[28] R. Cavalli, F. Trotta and W. Tumiatti,
Cyclodextrin-based nanosponges for drug
delivery, J. Incl. Phenom. Macrocycl. Chem. 56
(2006) 209–213; DOI:10.1007/s10847-006-
9085-2.
[29] F. Trotta, V. Tumiatti, R. Cavalli, C. Roggero,
B. Mognetti and G. Berta, Cyclodextrin-based
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
Nano- sponges as a Vehicle for Antitumoral
Drugs, WO 2009/003656 A1; 2009.
[30] F. Trotta and T. Wander, Cross-linked
Polymers Based on Cyclodextrins for
Removing Polluting Agents, WO 2003/085002,
US20050154198 A1, 14 July. 2005.
[31] S. Swaminathan, P. Vavia, F. Trotta and S.
Torne, Formulation of beta-cyclodextrin based
nano- sponges of Itraconazole, J. Incl. Phenom.
Macrocycl. Chem. 57 (2007) 89–94;
DOI:10.1007/s10847-006-9216-9.
[32] A. Mele, F. Castiglione, L. Malpezzi, F.
Ganazzoli, G. Raffaini, F. Trotta, B. Rossi, A.
Fontana and G. Giunchi, HR MAS NMR,
powder XRD and Raman spectroscopy study of
inclusion phenom- ena in b-CD nanosponges, J.
Incl. Phenom. Macrocycl. Chem. 69 (2011)
403–409; DOI:10.1007/ s10847-010-9772-x.
[33] S. Swaminathan, P. Vavia, F. Trotta, R. Cavalli,
P. Ferruti, E. Ranucci and I. Gerges, Release
mod- ulation and conformational stabilization
of a model protein by use of swellable
nanosponges of b-cyclodextrin, First European
Cyclodextrin Conference, Aalborg, Denmark
2009.
[34] S. Torne, K. Ansari, P. Vavia, F. Trotta and R.
Cavalli, Enhanced oral bioavailability after
admin- istration of paclitaxel-loaded
nanosponges, Drug Deliv. 17 (2010) 419–425;
DOI:10.3109/10717541003777233.
[35] K. Ansari, P. Vavia, F. Trotta and R. Cavalli,
Cyclodextrin-based nanosponges for delivery
of resveratrol: in vitro characterisation,
stability, cytotoxicity and permeation study,
AAPS Pharm SciTech, 12 (2011) 279–286;
DOI:10.1208/s12249-011-9584-3.
[36] E. Patel and R. Oswal, Nanosponge and micro
sponges: a novel drug delivery system, Int. J.
Res. Pharm. Chem. 2 (2012) 237–244.
[37] T. Loftsson and M. Brewster, Pharmaceutical
applications of cyclodextrins: drug
solubilization and stabilization, J. Pharm.
Pharmacol. 85 (1996) 1017–1025;
DOI:10.1021/js950534b.
[38] A. Radi and S. Eissa, Electrochemical study of
indapamide and its complexation with b-cyclo-
dextrin, J. Incl. Phenom. Macrocycl. Chem. 71
(2011) 95–102; DOI:10.1007/s10847-
010.9906-1.
[39] H. Bricout, F. Hapiot, A. Ponchel, E. Monflier
and S. Tilloy, Chemically modified
cyclodextrins: an attractive class of
Page 845
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
supramolecular hosts for the development of
aqueous biphasic catalytic processes,
Sustainability 1 (2009) 924–945;
DOI:10.3390/su1040924.
[40] H. Dodziuk, Molecules with Holes –
Cyclodextrins, in Cyclodextrins and Their
Complexes (Ed. H. Dodziuk), Wiley-VCH
Verlag GmbH & Co. KGaA, Weinheim 2006,
pp. 1–30.
[41] D. Li and M. Ma, Nanosponges for water
purification, Clean Prod. Process. 2 (2000)
112–16; DOI:10.1007/s100980000061.
[42] E. Bilensoy and A. Atilla, Cyclodextrin-based
Nanomaterials in Pharmaceutical Field, in
Pharmaceuti- cal Sciences Encyclopedia: Drug
Discovery, Development, and Manufacturing,
John Wiley & Sons Inc. Publishers 2010;
DOI:10.1002/9780470259818.ch31.
[43] R. Lala, A. Thorat and C. Gargote, Current
trends in b-cyclodextrin based drug delivery
sys- tems, Int. J. Res. Ayur. Pharm, 2 (2011)
1520–1526.
[44] B. Mamba, R. Krause, T. Malefetse and S.
Sithhole, Cyclodextrin nanosponges in the
removal of organic matter to produce water for
power generation, Water SA, 34 (2008) 657–
660.
[45] B. Mamba, R. Krause, T. Malefetse, S.
Mhlanga, S. Sithhole, K. Salipira and E.
Nxumalo, Re- moval of geosmin and 2-
methylisoborneol (2-MIB) in water from
Zuikerbosch water treatment plant (Rand
Water) using b-cyclodextrin polyurethane,
Water SA, 32 (2007) 223–228.
[46] S. Tang, L. Kong, J. Ou, Y. Liu, X. Li and H.
Zou, Application of cross-linked b-cyclodextrin
polymer for adsorption of aromatic amino acid,
J. Mol. Recogn. Macrocyclic Chem. 19 (2006)
39– 48; DOI: 10.1002/jmr.756.
[47] F. Trotta, R. Cavalli, S. Swaminathan, C.
Sarzanini and P. Vavia, Novel functionalized
nano- sponges: synthesis, characterization.
Safety assessment, cytotoxicity testing and
interaction stu- dies. Proceedings of the 14th
International Cyclodextrin Symposium, Kyoto
2008, pp. 338–342.
[48] G. Yurtdas, M. Demirel and L. Genc, Inclusion
complexes of fluconazole with b-cyclodextrin:
physicochemical characterization and in vitro
evaluation of its formulation, J. Incl. Phenom.
Ma- crocycl. Chem. 70 (2011) 429–435;
DOI:10.1007/s10847-010-9908-z.
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
[49] A. Rasheed, Cyclodextrins as drug carrier
molecule: a review, Sci. Pharmac. 76 (2008)
567–598; DOI:10.3797/scipharm.0808-05.
[50] P. Sinko, Martin’s Physical Pharmacy and
Pharmaceutical Sciences, 5th ed., Lippincott
Williams & Williams Publishers, Philadelphia
2006, p. 466.
[51] T. Govender, S. Stolnik, M. Garnett, L. Illum
and S. Davis, PLGA nanoparticles prepared by
na- noprecipitation: drug loading and release
studies of a water soluble drug, J. Control.
Release 57 (1999) 171–185;
DOI:10.1016/S0168-3659(98)00116-3.
[52] S. Galindo-Rodriguez, E. Allémann, H. Fessi
and E. Doelker, Physicochemical parameters
asso- ciated with nanoparticle formation in the
salting-out, emulsification-diffusion and
nanoprecipi- tation methods, Pharm. Res. 21
(2004) 1428–1439;
DOI:10.1023/B:PHAM.0000036917.75634.be.
[53] M. Leroueil-Le Verger, L. Fluckiger, Y. Kim,
M. Hoffman and P. Maincent, Preparation and
char- acterization of nanoparticles containing
an antihypertensive agent, Eur. J. Pharm.
Biopharm. 46 (1998) 137–143;
DOI:10.1016/S0939-6411(98)00015-0.
[54] N. Santos-Magalhães, H. Fessi, F. Puisieux, S.
Benita and M. Seiller, An in-vitro release
kinetic examination and comparative evaluation
between submicron emulsion and polylactic
acid na- nocapsules of clofibride, J.
Microencapsul. 12 (1995) 195–205;
DOI:10.3109/02652049509015290.
[55] A. Layre, R. Gref, J. Richard, D. Requier, H.
Chacun, M. Appel, A. Domb and P. Couvreur,
Na- noencapsulation of a crystalline drug, Int.
J. Pharm. 298 (2005) 323–327;
DOI:10.1016/j.ijpharm.2005.02.039.
[56] D. Lemoine, C. Francois, F. Kedzierewicz, V.
Preat, M. Hoffman and P. Maincent, Stability
study of nanoparticles of poly(b-caprolactone),
poly(D, L-lactide) and poly(D, L-lactideco-
glycolide), Biomaterials 17 (1996) 2191–2197.
DOI: 10.1016/0142-9612(96)00049-X.
[57] Y. Jeong, Y. Shim, C. Kim, G. Lim, K. Choi
and C. Yoon, Effect of cryoprotectants on the
recon- stitution properties of surfactant-free
nanoparticles of poly (D, L-lactide-co-
glycolide), J. Micro- encapsul. 22 (2005) 593–
601; DOI:10.1080/02652040500162659.
[58] H. Redhead, S. Davis and L. Illum, Drug
delivery in poly(lactide-co-glycolide)
nanoparticles surface modified with poloxamer
Page 846
 International Journal of Trend in Scientific Research and Development @ www.ijtsrd.com eISSN: 2456-6470
407 and poloxamine 908: in vitro
characterisation and in vivo evaluation, J.
Control. Release, 70 (2001) 353–363;
DOI:10.1016/S0168-3659(00)00367-9.
[59] M. Bivas-Benita, S. Romeijn, H. Junginger and
G. Borchard, PLGA-PEI nanoparticles for gene
delivery to pulmonary epithelium, Eur. J.
Pharm. Biopharm. 58 (2004) 1–6;
DOI:10.1016/j.ejpb.2004.03.008.
[60] R. Pecora, Dynamic light scattering
measurement of nanometer particles in liquids,
J. Nanopar- ticle Res. 2 (2000) 123–131; DOI:
10. 1023/A:1010067107182.
[61] M. Santander-Ortega, A. Jódar-Reyes, N.
Csabac, D. Bastos-González and J. Ortega-
Vinuesa, Colloidal stability of Pluronic F68-
coated PLGA nanoparticles: a variety of
stabilisation mecha- nisms, J. Colloid. Interf.
Sci. 302 (2006) 522–529;
DOI:10.1016/j.jcis.2006.07.031.
[62] Y. Ishikawa, Y. Katoh and H. Ohshima,
Colloidal stability of aqueous polymeric
dispersions: ef- fect of pH and salt
concentration, Colloid Surf. B 42 (2005) 53–
58; DOI:10.1016/j.colsurfb.2005.01.006.
[63] J. Shar, T. Obey and T. Cosgrove, Adsorption
studies of polyether’s- Part1: Adsorption onto
hy- drophobic surfaces, Colloid Surf A:
Physicochemical and Engineering Aspects 136
(1998) 21–33, DOI:10.1016/S0927-
7757(97)00182-9.
[64] E. Leo, B. Brina, F. Forni and M. Vandelli, In
vitro evaluation of PLA nanoparticles
containing a lipophilic drug in water-soluble or
insoluble form, Int. J. Pharm. 278 (2004) 133–
141, DOI: 10.1016/j.ijpharm.2004.03.002.
[65] U. Bilati, E. Allemann and E. Doelker,
Development of a nanoprecipitation method
intended for the entrapment of hydrophilic
drugs into nanoparticles, Eur. J. Pharm. Sci. 24
(2005) 67–75; DOI:
10.1016/j.ejps.2004.09.011.
[66] M. Bivas-Benita, S. Romeijn, H. Junginger and
G. Borchard, PLGA-PEI nanoparticles for gene
delivery to pulmonary epithelium, Eur. J.
Pharm. Biopharm. 58 (2004) 1–6;
DOI:10.1016/j.ejpb.2004.03.008.
[67] H. Fessi, F. Puisieux, J. Devissaguet, N.
Ammoury and S. Benita, Nanocapsule
formation by in- terfacial polymer deposition
following solvent displacement, Int. J. Pharm.
@ IJTSRD | Unique Paper ID – IJTSRD49469 | Volume – 6 | Issue – 3 | Mar-Apr 2022
55 (1989) R1-R4; DOI:10.1016/0378-
5173(89)90281-0.
[68] M. Chorny, I. Fishbein, H. D. Danenberg and
G. Golomb, Lipophilic drug loaded
nanospheres prepared by nanoprecipitation:
effect of formulation variables on size, drug
recovery and re- lease kinetics, J. Control.
Release 83 (2002) 389–400;
DOI:10.1016/S0168-3659(02)00211-0.
[69] V. Mosqueira, P. Legrand, H. Pinto-
Alphandary, F. Puisieux and G. Barratt, Poly
(D, L-lactide) nanocapsules prepared by a
solvent displacement process: influence of the
composition on physicochemical and structural
properties, J. Pharm. Sci. 89 (2000) 614–626;
DOI: 10.1002/(SICI)1520-
6017(200005)89:5<614::AID-JPS7>3.0.CO;2-
7.
[70] J. Ren, H. Hong, J. Song and T. Ren, Particle
size and distribution of biodegradable poly-D,
L-lactide-co-poly(ethylene glycol) block
polymer nanoparticles prepared by
nanoprecipitation, J. Appl. Polym. Sci. 98
(2005) 1884–1890; DOI: 10.1002/app.22070.
[71] M. Teixeira, M. Alonso, M. Pinto and C.
Barbosa, Development and characterization of
PLGA nanospheres and nanocapsules
containing xanthone and 3methoxyxanthone,
Eur. J. Pharm. Bio- pharm. 59 (2005) 491–500;
DOI: 10.1016/j.ejpb.2004.09.002.
[72] M. Tobìo, R. Gref, A. Sanchez, R. Langer and
M. Alonso, Stealth PLA-PEG nanoparticles as
pro- tein carriers for nasal administration,
Pharm. Res. 15 (1998) 276–279;
DOI:10.1023/A:1011922 819926.
[73] H. Brittain, D. Bogdanowich, J. DeVincentis,
G. Lewen and A. Newman, Physical
characteriza- tion of pharmaceutical solids,
Pharm. Res. 8 (1991) 963–973.
DOI:10.023/A:1015888520352.
[74] M. Hombreiro-Perez, J. Siepmann, C. Zinutti,
A. Lamprecht, N. Ubrich, M. Hoffman, R. Bod-
meier and P. Maincent, Non-degradable
microparticles containing a hydrophilic and/or a
li- pophilic drug: preparation, characterization
and drug release modeling, J. Control. Release
88 (2003) 413–428; DOI: 10.1016/S0168-
3659(03)00030-0.
[75] M. Guyot and F. Fawaz, Nifedipine loaded-
polymeric microspheres: preparation and
physical characteristics, Int. J. Pharm. 175
(1998) 61–74; DOI:10.1016/S0378-
5173(98)00253-1.
Page 847