COMPREHENSIVE REVIEW ON ICARIIN DRUG DELIVERY SYSTMES IN

CANCER TREATMENT
A Presentation on
the thesis submitted in the partial fulfilment for the Award of
the Degree of
BACHELOR OF PHARMACY

By
ANNI KUMARI
Reg No- 221055101107

Under the Guidance of

Dr. L Rajesh Patro
Professor
Department of Pharmacy
Usha Martin University, Anagra
Ranchi – 835103 (Jharkhand)
2024. 1
 Contents

INTRODUCTION

 LITERATURE REVIEW

 PLAN OF WORK

 ICARIIN DRUG DELIVERY SYSTEMS IN CANCER TREATMENT

 STRATEGIES AND OVERVIEW OF ICARIIN WITH CANCER TREATMENT

 PHARMACOLOGICAL APPLICATION OF ICA

 RESULT AND DISCUSSION

 CONCLUSION

REFERENCES
INTRODUCTION
 Introduction
 Cancer is one of the major causes of mortality and morbidity and globally accounts for more than 8 million
deaths. A recently published study reported that in 2021, approximately 2 million newer cancer cases were
diagnosed, and more than 0.6 million deaths were confirmed in the United States

 Undoubtedly, various newer anticancer drugs have been developed and repurposed and take care of this
situation, but most of these anticancer drugs exhibit multiple arrays of toxicities. Hence, it is important to
address this situation as it directly affects patients' quality of life.

 Icariin is a flavonoid glycoside compound with a variety of pharmacological activities and is the main active
component of the extract of Herba Epimedium. In early studies, the studies on ICA were mainly focused on
enhancing reproductive function and anti-aging.
 A series of studies have shown that ICA can inhibit tumor cell growth by regulating multiple pathways,
including inhibiting tumor cell proliferation and migration, inducing cell differentiation and apoptosis,
regulating autophagy, and blocking cell cycle, etc .
 ICA has meaningful potential application value in the future research of anticancer drugs. Therefore, it is
urgent that the principal overview on the research progression on ICA in cancers and the emphasis on the
future directions, which is much helpful for the development of clinical application of ICA in cancer
treatment.

 Icariin’, ‘ICA’, ‘Active ingredients of Epimedium’, ‘flavonoid glycoside compound’, ‘breast cancer’,
‘colorectal cancer’, ‘hepatocellular carcinoma’, ‘ovarian cancer’ and ‘esophageal cancer’. As the main active
ingredient of Epimedium extract, flavonoids are also important chemical classification markers.

 New and emerging delivery systems, including nano/microscale, have guided the pharmacy field, due to their
possible contributions in the improving properties such the BA and absorption, as well as promising clinical
applications
LITERATURE REVIEW
MICROSPHERE

 Apninder et al., 2012-Oral colon specific drug delivery system could enhance the systemic bio-availability of poor
absorbed drugs as the long retention time in colon. UC is a chronic intestinal inflammation with complex
pathogenesis. Icariin, the main active flavonoid glucoside isolated from Herba epimedii (Epimedium
brevicornum Maxim.), has been confirmed to have numerous pharmacological activities, such as anti-aging, anti-
tumor, and anti-inflammatory effects.

NANOEMULSION

 Chabra et al.,2014- To improve the therapeutic efficacy of ICR after oral administration, the first time a novel ICR
nanoemulsion (ICR-NE) was developed. NE was chosen as an effective nano-based delivery system because it is
known to increase the solubility and bioavailability of many lipophilic therapeutic actives.
 Quagliariello et al.,2014- optimized and developed NE of lycopene and studied its cardioprotective effect against
Dox-induced cardiotoxicity. The outcome of the study showed that the nanoformulation of lycopene exhibited
superior antioxidant, anti-inflammatory, and cardioprotective activity compared to the conventional formulation.

 Bali et al., 2015- fabricated a NE of ezetimibe, a non-stain lipid-lowering agent, and exhibited an additional
cardioprotective effect. Ezetimibe suffers from pharmacokinetic limitations. Hence, its NE was fabricated, showing
improved absorption and shelf life (18.5 months) compared to the marketed formulation

NEBULIZATION DELIVERY
 Chuan-Ke-Zhi 2000- that consists of purified Herba Epimedium extract, was officially approved by the National
Medical Products Administration of China in 2001 for the treatment of recurrent respiratory infections, asthma and
chronic obstructive pulmonary disease
 Yi-jun-cong 2004- Phospholipid-based particles have been the preferred choice for inhalable sustained release
systems as far as the clinical transition potential is concerned. Among the phospholipid-based particles, liposomes
represent particularly suitable drug carriers for sustained pulmonary administration.

PARENTERAL DELIVERY

 Al-mahallawi et al,. 2013-a novel nanocarrier represented by bilosomes, a bile salts-based niosomal system, was
selected. Bilosomes are highly deformable and more flexible compared to previously reported nanocarriers such as
liposomes and niosomes.

 C.J Porter et al., 2014- The relavent studies were selected by using the following keywords in various
combinations:‘Icariin’, ‘ICA’, ‘Active ingredients of Epimedium’, ‘flavonoid glycoside compound’, ‘breast cancer’,
‘colorectal cancer’, ‘hepatocellular carcinoma’, ‘ovarian cancer’ and ‘esophageal cancer’
PLAN OF WORK
 To do a strong and comprehensive literature survey on the icariin use on cancer treatment.

 Comprehensive review of icariin drug delivery system.

 Review strategies of cancer treatment with icariin.

 ICARIIN DRUG DELIVERY SYSTEMS IN CANCER TERATMENT

 ORAL DRUG DELIVERY SYSTEMS

1. Microsphere- Colon cancer treatment

2. Nano emulsion – Pancreatic cancer

 NEBULIZATION DRUG DELIVERY SYSTEMS

1. Pulmonary Cancer

 PARENTERAL DRUG DELIVERY

1. Polymeric Micelles

2. Liposomes with bilosomes melittin for pancreatic cancer

STRATEGIES FOR TREATMENT OF CANCER
 OVERVIEW OF BIOLOGICAL EFFECT OF ICA IN DIFFERENT CANCER

EFFECTS FUNCTIONS TYPES OF STUDES CANCER TYPES

Growth and Proliferation Inhibition Vitro and vivo Breast cancer

Colorectal cancer
Esophageal cancer
Ovarian cancer
Hepatocellular carcinoma
Acute promyelocytic leukemia
Pancreatic cancer

Migration and invasion Inhibition Vitro and vivo Breast cancer

Colorectal cancer
Esophageal cancer
Ovarian cancer
Gastric cancer
Pancreatic cancer
Apoptosis Promotion Vitro and vivo Breast cancer
Colorectal cancer
Esophageal cancer
Ovarian cancer
Hepatocellular carcinoma
Acute promyelocytic leukemia
Pancreatic cancer

Autophagy Inhibition Vivo Breast cancer

Ovarian cancer
Drug resistance Improvement Vivo Breast cancer
Colorectal cancer
Ovarian cancer
Hepatocellular carcinoma
PHARMACOLOGICAL APPLICATION OF ICA
RESULT AND DISCUSSION
 RESULT AND DISCUSSION

The treatment of cancer with icarrin has been research hot topic in the medical community. Therefore, we
belive that with the futher research in pharmacology, molecular biology and chemistry, ICA will be used as
representative and new generation of anti- cancer drug delivery system, which might further promotes the rapid
development of new strategies of drug delivery in the clinical treatment of cancer ICA can inhibit the growth,
migration, invasion and drug resistance of tumor cells through a variety of ways, and induce apoptosis of tumor
cells, with no side effects on normal cells, suggesting that ICA may be a new generation of candidate drugs for
cancer treatment in the future, and has a broad application prospect in clinical treatment. Besides, the growth of
tumor cells also depends on the generation of blood vessels, so the effective inhibition on the generation of
blood vessels will become a new treatment strategy for cancer. Recently, ICA has been reported to inhibit the
generation of blood vessels in vitro. Therefore, using ICA as an antiangiogenic agent to inhibit the generation
of blood vessels may be a new way to treat cancer.
CONCLUSION
 CONCLUSION
The present review demonstrates that cancer is a multifactorial disease as certain genetic and environmental factors increase
the incidence of this disorder. The genetic factors and their association with environmental factors also play an important
part. Avoiding exposure to these factors can decrease the incidence of cancer. Some substances extracted from natural
resources are able to induce an immune response, anti-tumor effects and inhibit proliferation of cancer cells. Hence,
innovative and efficient strategies utilizing natural products with improved survival rates and lesser adverse effects can be
recommended for cancer prevention. The described natural products in this review have been used as important contributors
to the discovery and development of new potential anticancer drugs as well as a likely substitute to resistance established by
cancer cells at a multidrug level ICA can inhibit the growth, migration, invasion and drug resistance of tumor cells through a
variety of ways, and induce apoptosis of tumor cells with no side effects on normal cells, suggesting that ICA may be a new
generation of candidate drugs for cancer treatment in the future, and has a broad application prospect in clinical treatment.
Besides, the growth of tumor cells also depends on the generation of blood vessels, so the effective inhibition on the
generation of blood vessels will become a new treatment strategy for cancer. Icariin (ICA) is easily hydrolyzed by bacteria in
the intestinal tract into baohuoside I and icaritin, thus significantly reducing ICA’s bioavailability. Nano-polymeric micelles
can improve the permeability of drugs through membranes, and effectively avoid drug loading digestion by intestinal
bacteria, which might serve as an important approach for improving drug bioavailability. As part of the trends in oral FDDS,
and according to the systematic screening of patent reported on Espacenet database, it could be found some different dosage

forms that includes a wide scope of formulations for oral administration .

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