PREPARATION OF FLUTAMIDE LOADED POLYMERIC NANOPARTICLES USING NANOPRECIPITATION APPROACH

Abstract

This research is to understand the various formulation techniques and develop new polymeric nanoparticles for targeting prostate cancer. Flutamide is a potent nonsteroidal anti androgen used in the treatment of prostate cancer. The present review concluded from the above discussion that the Flutamide loaded polymeric nanoparticles prepared with nanoprecipitation and synthetic polymers shown versatile characteristics like targeting action, sustained release, biodegradable and biocompatible nature acts as a best nanocarrier for the prostate cancer therapy when compared to nanoparticles prepared with other techniques and natural polymers. Polymeric nanoparticles can achieve autotargeted drug delivery via passive targeting based on the enhanced permeation and retention effect, or active targeting by an appropriate ligand, which improves antitumor efficacy and reduces toxicity on healthy tissues. For further advancement, it may be necessary to focus more research attention on the pharmacokinetics, biodistribution, and safety of these novel drug delivery.

Specification

Description:FIELD OF INVENTION:
[0001] The main objective of review of this research is to understand the various formulation techniques and develop new polymeric nanoparticles for targeting prostate cancer.

BACKGROUND:
[0002] Due to the growth and aging of the global population, Prostate cancer is the sixth leading cause of cancer death among men worldwide. The worldwide Prostate cancer burden is expected to grow to 1.7 million new cases and 4,99,000 new deaths by the year 2030.

[0003] Prostate cancer is the fourth most common cancer in both sexes combined and the second most common cancer in men. Prostate cancer has become a major health problem in industrialized world during the last decades of the 20th century contributing to three fourth of the registered cases across the globe. Incidence rates of prostate cancer vary by more than 25fold worldwide, the highest rates being in Australia/New Zealand (104.2/100,000), Western and Northern Europe and North America. Although incidence rates of prostate cancer are considered low in Asian and North African countries, ranging from 1 to 9/100,000 persons [4], demographic and epidemiological transitions in India have shown an increasing trend in the burden of various cancer cases including prostate cancer.

SUMMARY:
[0004] Flutamide is a potent nonsteroidal anti androgen that is used in the treatment of advanced prostate cancer. It blocks the androgen receptors on the cancer cells and inhibits the androgen dependent cell growth. The usual oral dose of flutamide is 250 mg three times daily. Its oral absorption is rapid and it attains peak plasma concentration in 1 h after a single dose. The drug has high first pass hepatic metabolism and low elimination half-life (5-6 h). Low functionality of flutamide is due to its rapid metabolism, less active metabolites (hydroxyl flutamide) and low bioavailability. Low bioavailability may be due to its poor wettability and low aqueous solubility. which reduce testosterone only on a continuous basis.

[0005] The high dose of Flutamide produces hepatotoxicity. Treatment with flutamide may cause a variety of side-effects including diarrhoea, tiredness, impotence, enlargement of male breast and liver malfunction [9]. In order to decrease the frequency of drug administration and also the incidence of adverse effects, a sustained release formulation of flutamide is desirable. Hence, the preparation of Flutamide formulations with high plasma half-life, slow and constant release which can deliver to the target tissue is important. Preparation of nanoparticles is a method that makes it possible to increase the bioavailability, reduce the incidence and severity of adverse effects, especially gastrointestinal disorders and hepatic impairment.

DESCRIPTION OF FIGURES AND TABLES:
[0006] Figure (0001): Structure of Flutamide

[0007] Figure (0002): Techniques for preparation of polymer Nanoparticles

[0008] Table (0001): Reported research work on Flutamide polymeric Nanoparticles

DETAILED DESCRIPTION:
[0009] Biodegradable polymers are advantageous in many ways over other materials used in drug delivery systems such as nanoparticles. In the literature, several polymeric nanoparticles have been developed, the natural polymers like chitosan and casein, the synthetic polymers like
Methacrylic acid, PHEA-IB-p(BMA) graft copolymer, mPEG - PLGA and PVA.

[0010] The present study was aimed to compile the published research work related to the formulation and evaluation of Flutamide loaded polymeric nanoparticles for the treatment of prostate cancer and study the influence of various formulation components on size, stability and release of nanoparticles. The objective of review article is to understand the various formulation techniques and develop new polymeric nanoparticles for targeting prostate cancer.

[0011] Natural Polymers: the polymer nanoparticles using chitosan, which the core: coat ratio 1:4 gives better sustained release for about 12 hrs as compared to other formulations. developed polymer nanoparticles using casein, which the drug and casein ratio 1:5 gives small particle size of 70.76 nm and better sustained drug release for about 14 hrs.

[0012] Synthetic Polymers: K. Umasankar, et.al., formulated flutamide nanoparticle using Methacrylic acid copolymer (RL100) with three different ratios. The particle size ranged between 335 nm to 620 nm and in vitro release was exhibited a sustained release up to 16 hrs Mariano Licciardi, et.al., 2013 prepared magnetic nanocarriers (MNCs) using the PHEA-IBp(BMA) graft copolymer as coating material, the nanocarriers showed dimensions of about 300 nm with superparamagnetic behaviour.

[0013] Dipsingh SN, investigation explores the use of methoxy polyethylene glycol (mPEG) functionalised poly(d,l-lactide-co-glycoside) (PLGA) nanocrystals. The optimised formulation exhibited significantly delayed drug release up to 48 hrs [14]. R. S. Surenya, et.al., Poly vinyl alcohol (PVA) coated flutamide nanoparticles exhibited sustained in vitro release up to 120 hrs.

[0014] PROCEDURE: The properties of polymer nanoparticles have to be optimized depending on the particular application. In order to achieve the properties of interest, the mode of preparation plays a vital role. As per literature, different techniques like nanoprecipitation, solvent evaporation and ionic gelation techniques were commonly used.

[0015] Ionic Gelation Method: This method involves a mixture of two aqueous phases, which one is the polymer chitosan / casein and the other is a polyanion sodium tripolyphosphate. In this method, positively charged amino group of chitosan interacts with negative charged tripolyphosphate to form coacervates with a size in the range of nano meter. The researchers Adlin jino nesalin j, et.al., and Ahmed O Elzoghby, et.al., developed nanoparticles of Flutamide by ionic gelation technique.

[0016] Solvent evaporation method: In this method polymer solutions were prepared using volatile solvents to formulate emulsions. The emulsion gets converted into a nanoparticle suspension on evaporation of the solvent from the polymer, which is allowed to diffuse through the continuous phase of the emulsion. In the literature K. Umasankar, et.al., 2010 and Mariano Licciardi, et.al., developed Flutamide nanoparticles by solvent evaporation method using dichloromethane and ethyl acetate as organic solvent.

[0017] Nanoprecipitation Method: It is based on the precipitation of preformed polymer following displacement of a semipolar solvent miscible with water in the presence or absence of surfactant. The easiest and reproducible technique for preparing nanospheres was nanoprecipitation method. In the literature Dipsingh SN. and R. S. Surenya, et.al., developed nanoprecipitation method for Flutamide nanoparticles and it shown highest encapsulation efficiency and percent cumulative drug release with spherical nanoparticles.

[0018] The prepared Flutamide polymeric nanoparticles characterised through differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electronic microscopy, particle size, zeta potential, percent entrapment efficiency (% EE), in vitro dissolution, haemolysis, sterility, bioavailability and stability studies.
, Claims:Claims:
I/We Claim:
1. A method of producing flutamide loaded polymeric nanoparticles for prostate cancer, comprising:
an ionic gelation method;
wherein this method involves a mixture of two aqueous phases, which one is the polymer chitosan or casein and the other is a polyanion sodium tripolyphosphate;
whereby positively charged amino group of chitosan interacts with negative charged tripolyphosphate to form coacervates with a size in the range of nanometer;
a solvent evaporation method;
wherein polymer solutions were prepared using volatile solvents to formulate emulsions;
the emulsion gets converted into a nanoparticle suspension on evaporation of the solvent from the polymer, which is allowed to diffuse through the continuous phase of the emulsion;
a nanoprecipitation method: wherein it is based on the precipitation of preformed polymer following displacement of a semipolar solvent miscible with water in the presence or absence of surfactant;
the easiest and reproducible technique for preparing nanospheres was nanoprecipitation method;
and wherein developed nanoprecipitation method for flutamide nanoparticles and it shown highest encapsulation efficiency and percent cumulative drug release with spherical nanoparticles.

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