Journal of Pharmaceutical Investigation (2017) 47:287–296
DOI 10.1007/s40005-017-0320-1
REVIEW
Mechanisms of drug release from advanced drug formulations
such as polymeric-based drug-delivery systems and lipid
nanoparticles
Gi‑Ho Son1 · Beom‑Jin Lee2 · Cheong‑Weon Cho1
Received: 30 January 2017 / Accepted: 6 March 2017 / Published online: 3 April 2017
© The Korean Society of Pharmaceutical Sciences and Technology 2017
Abstract Drug release from a polymeric nanocarrier is
affected by several factors including the sort of composi-
tion (drug, polymer, and excipient), the ratio of composi-
tion, physical or chemical interaction between components,
and manufacturing methods. Depending on the mechanism
of drug release from the vehicles, it can be divided into four
categories (diffusion, solvent, chemical interaction, and
stimulated release). Recently, lipids have attracted great
interest as carriers for water-insoluble drug delivery. Lipid-
based drug-delivery systems have received a lot of interest
because of their ability to improve solubility and bioavail-
ability of drugs that are poorly soluble in water. The lipid
carrier, formulation strategy, and rational drug-delivery
system should be selected appropriately for a lipid-based
drug-delivery system to be successful. In this review, the
general release characteristics and mechanisms of drug
from nanocarriers will be discussed.
Keywords Drug release · Polymeric nanocarrier · Lipid
nanoparticles · Release mechanism
* Beom‑Jin Lee
bjl@ajou.ac.kr
* Cheong‑Weon Cho
chocw@cnu.ac.kr
1
College of Pharmacy, Chungnam National University, 99
Daehak‑ro, Yuseong‑gu, Daejeon 34134, Republic of Korea
2
College of Pharmacy, Ajou University, Suwon 16499,
Republic of Korea
Online ISSN 2093-6214
Print ISSN 2093-5552
Introduction
With the improvement of drug design methods, many
potentially active substances have been manufactured and
synthesized. However, most recently developed drugs
belong to biopharmaceutical classification system (BCS)
groups 2 or 4, which have low aqueous solubility. Low
water solubility of drugs limits their absorption in the
body and reduces their oral bioavailability (Amidon et al.
1995). To make these drugs safe and effective for treat-
ment, a number of factors including bioavailability, for-
mulation characteristics, and body disposition must be
considered. Thus, attempts using micronization, formation
of complexes with cyclodextrin, solid dispersions, permea-
tion enhancers, and surfactants have been made to solve
the issues of dissolution and permeation of drugs (Aungst
1993). The goal of drug release from a carrier is to main-
tain and control the drug concentration in the blood and
target tissue. The first paper describing a sustained drug-
release system consisting of a polymeric device was pub-
lished in 1964 (Folkman and Long 1964), and a number of
delayed drug-delivery systems controlled by polymers have
begun to be investigated.
Several models of release kinetics can be used to illus-
trate drug release from drug-delivery systems, such as the
drug-release kinetic mechanisms controlled by the barrier
surrounding the matrix and regulated by drug diffusion
through a carrier matrix. In addition, degradation or swell-
ing of the carrier matrix and loss of drug–polymer linkage
can also control the rate of drug release from the carrier
(Bajpai et al. 2008; Freiberg and; Zhu 2004). Recently,
various nanocarriers have been developed to improve the
effectiveness of drug delivery (Lee and Yeo 2015) (Fig. 1).
Although the spatial control of drug delivery based on
nanocarriers has been widely studied (Acharya and Sahoo
13
Vol.:(0123456789)
288
Fig. 1  Various types of phar- (a)
maceutical nanocarriers for
drug delivery. a nanocapsule; b
nanosphere; c liposome Drug
Nanocapsule
2011; Brannon-Peppas and Blanchette 2004; Lu and Low
2002; Maeda et al. 2013; Xu et al. 2013), the importance
of controlling drug release from carriers at a nanoscale is
sometimes neglected because large-scale drug-delivery sys-
tems are well established. However, because nanocarriers
have a larger surface area per volume and a short diffusion
distance, the control of drug release from nanoparticles
faces different challenges compared with classical drug
carriers.
Drug‑release mechanism from polymeric
nanocarriers
One of the primary goals of controlling drug release is
to keep the concentration of drug in the blood within the
therapeutic range (Siegel and Rathbone 2012). Therefore,
it is ideal to develop drug carriers that have low dosing
frequency and provide controlled drug release. To achieve
this, drug-delivery systems that have a zero-order drug-
release profile in which the drug is uniformly released have
been pursued (Bajpai et al. 2008; Siegel and Rathbone
2012). Drug release from a nanocarrier is affected by sev-
eral factors including the sort of composition (drug, poly-
mer, and excipient), the ratio of composition, physical or
chemical interaction among components, and manufactur-
ing methods. Depending on the mechanism of drug release
out of the vehicles, drug release can be divided into four
categories (diffusion, solvent, chemical interaction, and
stimulated release), as shown in Fig. 2 (Langer and Peppas
2006; Siegel and Rathbone 2012).
Diffusion‑controlled release
Diffusion-controlled drug release occurs in capsule-like
systems where the drug is dissolved or dispersed in a core
(Cauchetier et al. 2003). The diffusion of the drug is caused
by the difference in concentration gradient across the mem-
brane (Crank 1975). Here, the drug is dissolved in the
central part and then diffuses through the membrane. The
matrix type nanospheres also have a diffusion-controlled
release profile, where the drug molecules are evenly dis-
persed in the polymer matrix. Matrix type systems do not
13
G.-H. Son et al.
(c)
(b)
Hydrophobic
drug
Hydrophilic
drug
Nanosphere
Liposome
Fig. 2  Various mechanisms of drug release from nanocarriers. a
diffusion-controlled release; b solvent-controlled release; c polymer-
degraded release; d pH-sensitive release
have membranes that can act as a barrier to diffusion. Thus,
such systems generally show a high initial release, but over
time, the release rate decreases as the drug molecule diffu-
sion distance inside the carrier increases.
Solvent‑controlled release
Transport of a solvent into drug-delivery systems may
affect drug-release behavior from the delivery carriers.
Solvent-controlled release includes osmotic- and swelling-
controlled release (Langer and Peppas 2006). Osmotic-
controlled release occurs in a carrier that is packed with a
semipermeable polymer membrane, and water flows from
the carrier with a low concentration of drug to the center of
the carrier with high drug concentration. As a result of this
mechanism, drug release with zero-order kinetics occurs
along a gradient of concentration that is constantly main-
tained across the membrane.
A swelling-controlled system is mainly composed of
polymer material having a three-dimensional cross-linked
network structure such as a hydrogel in which mesh size
controls drug-release behavior. (Lin and Metters 2006;
Peppas et al. 2000). Drug release from hydrogels can
Mechanisms of drug release from advanced drug formulations such as polymeric-based…
be analyzed by the semiempirical Peppas model ­ ( M t/
M∞ = ktn), where ­Mt and ­M∞ are the absolute accumula-
tions of drug released at time t and infinite time, respec-
tively, k is a constant, and n is the release index. This
equation makes it possible to determine the release mech-
anism (Hayashi et al. 2005; Korsmeyer et al. 1983; Pep-
pas et al. 2000; Ritger and Peppas 1987; Siepmann and
Peppas 2001). Swelling-controlled systems can achieve
zero-order drug release, depending on the initial drug
distribution of the system (Lee 1984) or polymer compo-
sition (Kaity et al. 2013).
Degradation‑controlled release
Drug carriers composed of biodegradable polymers such
as polyesters, polyamides, and polysaccharides release
the drug through enzymatic decomposition, which
degrades ester or amide bonds, or causes hydrolysis (Lee
et al. 2011; Prabaharan et al. 2009; Yoo and Park 2001).
A matrix composed of polymers such as polylactic-co-
glycolic acid (PLGA), polylactic acid (PLA), or polycap-
rolactone (PCL) undergoes a degradation process, and
consequently the overall matrix is degraded simultane-
ously. By contrast, a matrix made from polymeric anhy-
drides or orthoesters typically erodes from the surface to
the center and then causes degradation of the polymer at
a faster rate than water diffuses into the matrix (Burk-
ersroda et al. 2002; Middleton and Tipton 2000). How-
ever, a small-sized matrix, such as those found in nano-
particles, has a very short diffusion length for water and a
limited crystallization zone. Polymer degradation contin-
ues to accelerate with overall polymer degradation rather
than only surface erosion (Lee and Chu 2008). Biode-
gradable polymer systems are preferred because they are
degraded in the body.
pH‑controlled release
The release of drugs from nanocarriers that respond to
stimuli is controlled by a stimulus such as temperature,
pH, ionic strength, ultrasound, electricity, or magnetic
fields (Abouelmagd et al. 2014). Such carriers have been
studied for targeted specific drug delivery because it is
possible to localize stimulation. For example, nanocarri-
ers connected with pH-sensitive linkers using the weakly
acidic pH of many solid tumors have been developed
as site-specific drug-delivery carriers (Min et al. 2010;
Talelli et al. 2010). In heat-sensitive drug-delivery sys-
tems, drugs are released using the phase transition tem-
perature of the heat-induced polymer (Chang et al. 2008;
Li et al. 2011).
289
Drug‑release mechanisms of drug from lipid based
nanocarriers
Recently, lipids have attracted a great deal of interest as
carriers for water-insoluble drug delivery. The availabil-
ity of useful lipid excipients capable of satisfying safety
aspects and having the ability to increase oral bioavail-
ability has contributed to the development of lipid-based
formulations. Lipid-based drug-delivery systems attract a
lot of interest because of their ability to improve solubil-
ity and bioavailability of poorly water-soluble drugs (Pou-
ton 2006). Drug absorption from lipid-based formulations
depends on many factors including particle size, degree of
emulsification, rate of dispersion, and drug precipitation in
dispersion (Jannin et al. 2008; Pouton 2000, 2006). A lipid
carrier formulation strategy and a rational drug-delivery
system should be selected appropriately for the lipid-based
drug-delivery system to be successful (Dahan and Hoffman
2008).
Lipid based nanocarriers
Self‑micro emulsifying drug‑delivery systems
(SMEDDS)
SMEDDS are isotropic, transparent, and thermodynami-
cally stable solutions containing oil, surfactant, and cosol-
vent/cosurfactant. SMEDDS are defined as systems capa-
ble of forming microemulsions of oil-in-water by simply
adding and gently agitating aqueous media such as gas-
trointestinal (GI) fluids (Mahesh et al. 2001; Patel et al.
2010). Microemulsion is characterized by small droplet
size (about 200 nm) and wide interface. The drug is dis-
solved in a droplet, and the large surface of the microemul-
sion increases the absorption rate in the body. SMEDDS
not only promote solubilization of the drug but also have
an advantage in terms of releasing and absorbing the drug
(Craig et al. 1995; Farah and Denis 2001). Thus, if the
release rate of poorly water-soluble drugs acts as a key
parameter for absorption, it is expected that SMEDDS will
improve the rate and extent of absorption, resulting in bet-
ter bioavailability (Gursoy and Benita 2004; Pouton 2000).
When SMEDDS are introduced by an oral route, emul-
sification occurs because of mixing with gastrointestinal
fluids. Thus, the mixture of surfactant and oil containing
drugs is reconstituted to small-sized microemulsion drop-
lets. Figure 3 shows the various phases that will appear
when an aqueous medium is introduced into SMEDDS
(Rajput et al. 2012).
The emulsified drug containing microemulsion drop-
lets promotes bile secretion and is additionally emulsified
by bile acid and bile salts. Figure 4 illustrates the process
13
290
Fig. 3  The various phases that result from the addition of water
phase to SMEDDS
by which SMEDDS are absorbed after they enter the body.
The lipid nanodroplets are metabolized by lipase of the
pancreas and are divided into fatty acid and 2-monoglyc-
erides. Short fatty acids are absorbed by direct diffusion
through the hepatic portal system, while long fatty acids
and monoglycerides are resynthesized into triglycerides
and surrounded by phospholipids, cholesterol, and lipopro-
teins. As a result, chylomicrons eventually are created and
absorbed through the lymphatic pathway (Agrawal et al.
2012).
Liposomes
A liposome has a spherical bilayer structure similar to a cell
membrane. The lipids predominantly used in the produc-
tion of liposomes are phospholipids having an amphipathic
hydrophilic head and a hydrophobic tail. These phospholip-
ids form a spherical bilayer structure in the hydrated state,
with the hydrophobic portion facing inward and the hydro-
philic portion facing outward. The advantage of a liposome
system is that the hydrophilic material can be buried in the
hydrophilic space at the center of the liposome, and hydro-
phobic materials can be trapped in the fatty acid inside the
13
G.-H. Son et al.
lipid bilayer. Figure 5 gives an overview of the various type
of liposomes that can be prepared by modifications, and the
models of drug-release kinetics from the liposome (Jain
and Jain 2016).
In general, drug release from liposomes depends on fac-
tors such as drug permeability and thermodynamic param-
eters such as drug distribution across bilayer surfaces. It is
known that in vitro sink conditions are intended to simulate
physiological states, and it is not easy to predict the com-
plexity of in vivo release processes (Jain and Jain 2016). To
establish better in vitro–in vivo correlations, release kinetic
studies were conducted in mathematical models with
appropriate approximation. Fugit and Anderson studied the
release patterns from liposomes in the nonsink environment
of topotecan, and they observed that drug release and distri-
bution between bilayer and aqueous phases followed first-
order release kinetics. Similar results were obtained after
a slight correction of the mathematical model when the
study was performed under sink conditions using dynamic
dialysis. Under nonsink conditions, mathematical modeling
was used to study the effect of drug dimerization and the
zeta potential on the drug distribution across bilayers (Fugit
and Anderson 2014). Dynamic dialysis is generally used to
study the kinetics of release from nanocarriers. Usually, the
drug is released from the nanocomposite and diffuses from
the dialysis membrane into the receiver portion of the sink
condition. Control of permeability is an important param-
eter in liposomes because it regulates active release, and
encapsulation serves to deliver the drug to the desired site
only. Drug-delivery systems based on liposomes may uti-
lize increased permeability of the phospholipid membrane
through gel–sol transfer in response to external stimuli
(e.g., temperature causing drug release at the target site).
Although numerous studies have reported that liposomes
can improve drug encapsulation and in vitro release, there
exists no comprehensive theory on membrane structure and
drug release or membrane transport (Schaefer et al. 2012).
Various dynamic models have been used to interpret drug
release from liposomes (Costa and Sousa Lobo 2001; Fugit
et al. 2015; Csuhai et al. 2015). There are various math-
ematical models for describing drug release from drug-
delivery systems, including the zero-order kinetic model,
the first-order kinetic model, the Higuchi model, the Hix-
son–Crowell model, the Korsmeyer–Peppas model, and the
regression model (Hayashi et al. 2005).
Solid lipid nanoparticle (SLN)
Recently, SLN has received much attention as a means of
increasing site-specific drug delivery and bioavailability.
Therefore, many studies have been conducted to explore the
possibility of transport through the small intestinal lymph
pathway. SLN is a spherical particle typically 10–1000 nm
Mechanisms of drug release from advanced drug formulations such as polymeric-based…
Fig. 4  Potential mechanism for absorption enhancement of SMEDDS
in diameter, and the core of the solid lipid is stabilized by
surfactant and can solubilize lipid-soluble drugs and mate-
rials. One of the biggest challenges when studying lipid
nanoparticles is that burst release may occur in this system.
A burst release phenomenon was observed in all encap-
sulated drugs in tetracaine and etomidate SLNs prepared
by hot homogenization or cold homogenization methods,
respectively (Schwarz 1995). By contrast, delayed release
was obtained in the study of the incorporation of predni-
solone to SLN. These results confirm the suitability of the
SLN system for long-term drug release. Importantly, it is
possible to alter the drug-release profile by controlling the
lipid matrix, the concentration of the surfactant, and factors
involved in the production (e.g., temperature) of the lipid
nanoparticles, and the effect of particle size is negligible.
In addition, manufacturing parameters such as surfactant
concentration, temperature, and inherent characteristics of
the lipid matrix are the greatest determinants of the drug-
release profile from lipid nanoparticles. During nanopar-
ticle manufacturing processes involving high-temperature
homogenization techniques, the drug is distributed from a
liquid lipid phase to an aqueous phase. As the solubility of
the drug increases in the aqueous phase, the amount of drug
distributed to the aqueous phase will be greater. As temper-
ature and concentration of the surfactant increase, the drug
saturation solubility of the aqueous phase increases in a
system composed of water containing surfactant, lipid, and
291
drug. In the cooling process of prepared oil-in-water type
nanoemulsions, the lower temperature of the aqueous phase
might reduce the solubility of drug. This means that the
drug is redistributed into the lipid. A schematic diagram of
this process is shown in Fig. 6 (Muller et al. 2000). When
the lipid reaches a recrystallization temperature, the solid
lipid core contains the drug. When the temperature of dis-
persion is lowered, the drug is redistributed to the lipid as
the solubility of the drug in water is reduced. This is related
to the pressure exerted on the drug. Because the drug can
no longer be present in the already crystallized lipid core,
the drug is consequently concentrated on the surface of
the SLN or the liquid outer layer. Thus, the extent of burst
release can be controlled through the surfactant concentra-
tion or the temperature setting during preparation. Higher
temperature and surfactant concentration increase burst
release, while production at room temperature does not
show any burst because it avoids the process of redistribu-
tion of the drug to the aqueous phase and subsequent redis-
tribution to the lipid. SLN without burst release may be
produced with a surfactant-free process. Based on Mehnert
and Mader (2001), there are three drug encapsulation mod-
els in SLN; namely, a solid solution model, a core–shell
model, and a drug-enriched shell and core–shell model
(Fig. 6).
When lipid nanoparticles are prepared by cold homog-
enization using no drug-solubilizing surfactant, the drug
13
292 G.-H. Son et al.

Fig. 5  Liposome modified in miscellaneous ways and various models of release kinetics from liposomes. a cationic or stimuli-sensitive lipo-
some; b release kinetics; c PEGylated or targeted liposomes; d conventional liposomes

is evenly dispersed on a molecular basis in the lipid
matrix, and this SLN matrix is a solid solution. The
model in which the drug is abundant in the outer shell
is because of drug redistribution during the cooling pro-
cess. A drug-enriched core is obtained when the drug is
precipitated before the lipid is recrystallized. This core is
obtained only when the drug is dissolved in the lipid at
or near saturation solubility. Cooling of the nanoemulsion
allows the drug to crystallize before crystallization of the
lipid, and the molten lipid will be supersaturated with the
drug. Additional cooling will lead to recrystallization of
the lipid surrounding the drug core as a membrane. This
lipid membrane will contain only drug content corre-
sponding to drug saturation solubility at lipid recrystal-
lization temperature. This means that a drug-rich core
is formed and surrounded by a lipid shell (Muller et al.
2000).
Nanostructured lipid carrier (NLC)
Unlike SLN, where the drug is encapsulated in solid lipids,
NLC refers to a system that encapsulates the drug in a mix-
ture of solid lipid and liquid lipid. In NLC, drug solubili-
zation capacity increases because of liquid oil; thus, this
system exhibits controlled release characteristics with the
advantage of high drug loading. In particular, incomplete
and amorphous types of NLCs provide more flexibility
to achieve a desired sustained release (Fig. 7). NLC with
more imperfections in the crystal structure as compared to
SLNs are prepared using a blend of solid lipid and spatially

13
Mechanisms of drug release from advanced drug formulations such as polymeric-based…
Fig. 6  Partitioning effects on drug during the production of SLN by a hot homogenization technique and three drug incorporation models [solid
solution model (left), drug-enriched shell models (middle) and lipid shell (right)]
Fig. 7  Schematic illustration of SLN and NLC structure
different liquid lipids. These imperfections contribute to
improved drug loading and reduced drug expulsion during
storage (O’driscoll and Griffin 2008; Zhuang et al. 2010).
Therefore, NLC which are lipid nanoparticles or colloidal
carriers have been explored as potential topical delivery
vehicle. NLC have been reported to offer several advan-
tages over conventional topical products owing to their
ability to prolong the drug release, mitigate skin irritation,
and protect of drug from potential degradable opportuni-
ties. Additionally, the high specific surface area of the par-
ticles ensures excellent contact with the affected site on the
skin, facilitating the transfer of drug more efficiently (Fang
et al. 2008).
NLC shows a drug-release pattern consisting of two
stages: an initial burst release followed by a sustained release
at a constant rate. The outer shell layer consisting of liquid
lipids is rich in the drug, which causes an initial burst release.
Unlike SLN, the outer layer of NLC where liquid lipid is
abundant can dissolve more lipophilic drugs. Thus, a consid-
erable amount of the drug can be easily loaded on the outer
293
shell and released by diffusion or erosion of the matrix. Fol-
lowing this initial rapid release, slow release appears from
the solid lipid core. The interesting aspect of NLC is that it
is possible to create a drug-release profile versus oil content
(Muller et al. 2002).
Drug‑release mechanisms
Peppas model
Korsmeyer et al. (1983) attempted to explain drug release as
a mathematical model (Korsmeyer–Peppas model) expressed
in terms of a log cumulative drug-release percentage versus
log time. This model is stated as: M ­ t/M∞ = Ktη. ­Mt/M∞ is
the fraction of drug released at time t, k is the release rate
constant, and η is the release index. The η value predicts
the release mechanism of the drug. In other words, 0.45 ≤ η
corresponds to the Fickian diffusion model, 0.45 < η < 0.89
to non-Fickian transport, η = 0.89 to Case II transport, and
η > 0.89 to Super Case II transport.
Higuchi model
Higuchi (1963) has developed a number of mathematical
theoretical models to identify the manner in which water-
soluble and lipid-soluble drugs are released from the various
matrix systems. These models are represented by the follow-
ing equation:
√
ft = Qt = D(2C − Cs)Ct
where ­Qt is the amount of drug released per unit area at
time t, C is the initial concentration of the drug, C
­ s is the
solubility of the drug, and D is the diffusion √
constant. The
Higuchi model can be simplified to ft = KH t. ­KH is the
13
294
Higuchi dissolution constant. Thus, Higuchi explained drug
release as a diffusion process based on Fick’s law (depend-
ing on the square root of time).
First‑order release kinetics model
The first-order kinetics model is expressed by the following
equation: log C = log C ­ 0 – k­ t/2.303. ­C0 is the initial drug
concentration, K is the first-order rate constant, and t is the
time. The release data are shown as the cumulative log per-
centage of remaining drug versus time and a straight line
with a slope of K/2.303 (Dash et al. 2010, England et al.
2015). Three parameter models for liposomes have been
reported, which include reversible drug-delivery interac-
tions and first-order release kinetics. This model is simple
and can be adapted to a wide range of nanocarriers using
different model parameters (Zeng et al. 2011).
Zero‑order release kinetics model
Slow drug release according to zero-order release kinetics
uses the following equation:
Dt = D0 + k0 t
where ­Dt is the amount of drug dissolved at time t, ­D0 is the
initial drug amount in the solution, and ­k0 is the zero-order
release rate constant (Dash et al. 2010). In the zero-order
release kinetics model, the drug-release data are expressed
as the cumulative amount of released drug versus time.
This release model can be useful for transdermal, oph-
thalmic, and poorly soluble drug delivery. The zero-order
release pattern is ideal for slow and delayed drug delivery
such as antibiotics, antidepressants, blood pressure regula-
tors, analgesics, and anticancer drugs (Knepp et al. 1987;
Fattal et al. 1991).
Weibull release model
The Weibull release rate model is an empirical model
widely used for both immediate and sustained drug-release
patterns. Factors affecting overall drug release including
effective surface area only depend on mass. This model is
expressed as:
dw D
= CskMk� tp
dt h membrane penetration spread (flip-flop) with simultane-
where kM = S, and k′tp = X.
Wei et al. (2014) developed a liposome containing bai-
calin to increase its oral bioavailability. This liposome
showed delayed release according to the Weibull release
rate model. In vivo studies have shown that oral bioavail-
ability increased threefold.
13
G.-H. Son et al.
Two‑film theory mathematical model
In two-film theory mathematical models, interfacial
reactions and diffusion resistances are studied to evalu-
ate drug release and nanoparticle permeability from
nanocrystals and liposomes. Small et al. (2012) used low-
frequency ultrasound (LFUS) to perturb the membrane.
Liposomes were prepared from POPC (1-palmitoyl-2-ole-
oyl-sn-glycero-3-phosphocholine), dipalmitoylphosphati-
dylcholine (DPPC), and cholesterol. Calcein release from
large unilamellar vesicles (LUV) was monitored after
LFUS (20 kHz) exposure following the two-film theo-
retical mathematical model. Interestingly, the increased
DPPC content increased permeability in response to
LFUS, while the permeability decreased when the molar
fraction of POPC and cholesterol increased.
Biomembrane model
Biomembrane models simulate natural cell membranes
because of similar lipid arrays (Sarpietro et al. 2013).
Interactions between physiologically active compounds
and lipids have been studied using differential scanning
calorimetry for a variety of purposes including drug
release from lipid vesicles to biomembrane models. The
interaction between physiologically active substances and
biological membranes was observed using heat effect. In
addition, various parameters (pH, swelling, and cross-
linking characteristics, etc.) have been found to influence
the release kinetics of bioactive molecules during DSC
analysis (Sarpietro and Castelli 2011).
Toroidal model
For a liposome, the toroidal model has been well stud-
ied in peptide release (Torchilin and Lukyanov 2003).
For example, delta-lysin causes concentration gradient
outflow of entrapped materials in phosphatidylcholine
(PC) vesicles. When fluorescence energy change was
used to study efflux effects and peptide-induced lipid flip-
flops, peptide transitions across bilayers were observed
with instantaneous agitation in the membrane. Sobko
et al. (2010) reported that the addition of the colicin E1
channel-forming domain to liposomes results in a lipid
ous release of fluorescent dye in the liposome. Colicin
reflects the formation of a large pore that can induce the
release of colicin in liposomes and can be formed by the
head moiety of lipid molecules (Sobko et al. 2010).
Mechanisms of drug release from advanced drug formulations such as polymeric-based…
Conclusions
The latest nanobased drug-delivery technology not only
provides increased solubility for poorly soluble drugs but
also can control drug-release rate and pattern. Through
studies of release mechanisms of nanocarrier into the body,
a true “controlled drug-delivery system” could be realized
in the near future.
Acknowledgements This work was supported by the Basic Sci-
ence Research Program (2016R1A2B4011294) through the National
Research Foundation of Korea (NRF) funded by the Ministry of Edu-
cation, Science and Technology.
Compliance with ethical standards
Conflict of interest All authors declare that they have no conflict
of interest.
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