formulation and evaluation of chitosan …:壳聚糖的制定和评价…

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1、FORMULATION AND EVALUATION OF NANOPARTICLES CONTAINING AN ANTICANCER DRUG SYNOPSIS FOR M. PHARM. DISSERTATION SUBMITTED TO RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA BY PRADEEP. D I M. PHARM. DEPARTMENT OF PHARMACEUTICS DAYANANDA SAGAR COLLEGE OF PHARMACY 2012 RAJIV GANDHI UNIVERSITY OF H

2、EALTH SCIENCES BANGALORE, KARNATAKA ANNEXURE-II PROFAMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION 1. Name of the candidate and address (in block letters) PRADEEP. D I M. PHARM., DEPARTMENT OF PHARMACEUTICS, DAYANANDA SAGAR COLLEGE OF PHARMACY, KUMARASWAMY LAYOUT, BANGALORE-560078. PERMANENT ADDR

3、ESS # 30,WARD NO:09,ARALEPETE,RAMANAGARA TALUK AND DISTRICT-562159 2.Name of the instituteDayananda Sagar College of Pharmacy, Shavige Malleswara Hills, Kumaraswamy Layout, Bangalore-560078, Karnataka. 3.Course of study and subjectMaster of Pharmacy in Pharmaceutics 4.Date of admission to course14 A

4、UG 2012 5.Title of the project: “FORMULATION AND EVALUATION OF NANOPARTICLES CONTAINING ANTICANCER DRUG” 6.Brief resume of the intended work: 6.1 Need of the study: Cancer is one of the major causes of death in many industrialized countries and its incidence is ever increasing. Deaths from cancer wo

5、rldwide are projected to continue rising, with an estimated 12 million deaths in 2030. Therefore, tremendous resources are being invested in prevention, diagnosis and treatment of cancer. Discovery and development of anticancer agents are the key focus of several pharmaceutical companies as well as

6、nonprofit government and non government organizations1. Treatment of cancer includes chemotherapy, radiation therapy, gene therapy, photodynamic therapy, biologic therapy, surgical removal of tumor cells, etc., of these methods chemotherapy is the most effective, convenient and non- expensive treatm

7、ent for tumor. The challenges of anticancer treatment by chemotherapeutic agents include nonselective delivery of cytotoxic drugs to tumor sites that lead to severe side effects due to their effects on normal non targeted organs and tissues2. In recent years, numerous nano-sized drug carriers, such

8、as micelles, nanoparticles, polymerdrug conjugates, and stealth liposomes, have been investigated in order to minimize side effects of anticancer drugs and enhance the antitumoral drug efficacy in cancer therapy. A critical advantage in treating cancer with nanoparticles is the inherent leaky vascul

9、ature present serving cancerous tissues. The defective vascular architecture, created due to rapid vascularization necessary to serve fast-growing cancers, coupled with poor lymphatic drainage allows an enhanced permeation and retention effect3. Targeting the tumor vasculature is a strategy that can

10、 allow targeted delivery to a wide range of tumor types. Tremendous opportunities exist for using nanoparticles as controlled drug delivery systems for cancer treatment. Natural and synthetic polymers including albumin, fibrinogen, alginate, chitosan, and collagen have been used for the fabrication

11、of nanoparticles. Hence considering the importance of treating caner, an attempt will be made to target and deliver an anti-cancer drug to these cancerous cells so as to minimize adverse effects, dose and also dosing frequency. This is achieved by formulating anticancer drugs in the form of nanopart

12、icles. 6.2 Review of literature Nanoparticles containing 5-fluorouracil-loaded N-succinyl-chitosan were prepared by an emulsification solvent diffusion method. The influence of the initial 5- fluorouracil concentration on the nanoparticle characteristics and release behaviour in phosphate-buffered s

13、aline solution was evaluated. The formulation with an initial 5-FU concentration of 1000 microg mL-1 provided the highest loading capacity and the highest extent of release. Hence this combination showed good anti-tumour activity against Sarcoma 180 solid tumour4. Adriamycin nanoparticles were prepa

14、red using biocompatible and biodegradable poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) polymers. The nanoparticles were prepared by precipitation-solvent evaporation technique. Particle sizes were between 65 and 100 nm for different compositions of PLGA- PEG copolymers. Entrapment effic

15、iency was 25%33%. Adriamycin release from the nanoparticles at pH 7.4 showed an initial burst release and then sustained release phase. These results showed that PLGA-PEG nanoparticles could be an effective carrier for cancer therapy5. Nanoparticles were developed with 5-fluorouracil (5-FU) loaded N

16、,O- carboxymethyl chitosan (N,O-CMC) for cancer drug delivery. Drug entrapment efficiency and in vitro drug release studies were carried out spectrophotometricaly. Results of anticancer activity showed the toxicity of the drug loaded nanoparticles towards breast cancer cells. The results indicated the reduction in side effects of conventional chemo treatment6. Curcumin loaded fibrinogen nanoparticles (CRC-FNPs) were prepared and evaluated as a novel drug delivery system for cancer therapy. Th

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