Drug Delivery Studies of Gold Nanoparticles Decorated Polylactic Acid-co-ethyl Cellulose Nanocapsules

The present work describes the synthesis and characterization of PLA-co-EC copolymer from lactic acid and ethyl cellulose by azeotropic dehydration, under reduced pressure, at 140oC for 8 hours. The prepared PLA-co-EC copolymer was used for controlled drug release for an anticancer drug namely 6-Thioguanine with gold nanoparticles. Anticancer drug containing PLAco-EC copolymer nanocapsules were prepared by solvent evaporation method in the presence and absence of gold nanoparticles. The drug entrapped nanocapsules were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The controlled drug release of anticancer drugs entrapped nanocapsules were carried out in 0.1M HCl and 0.1M phosphate buffer (pH-7.4). The results indicated that the drug release for gold nanoparticles/anticancer drug (Au@Drug) incorporated PLA-co-EC nanocapsules was controlled and slow compared to drug incorporated PLA-co-EC nanocapsules. This may be due to the strong interaction between the gold nanoparticles and anticancer drug in PLA-co-EC nanocapsules. However the drug release was found to be slow in 0.1M HCl compared to 0.1M PBS which may be due to the solubility characteristics of both the nanoparticles and the copolymer. Hence, gold nanoparticles act as good trapping agents which slow down the rate of drug release from nanocapsules. KEY WORD Anticancer drug, Nanocapsules, Dehydration, Phosphate buffer, Lactic acid. INTRODUCTION Nanoencapsulation of drugs involves the formation of drug loaded particles with diameters ranging from 1 to 1000 nm. Nanoparticles are defined as solid, submicron sized drug carriers that may International Journal of Advanced Engineering Technology IJAET/Vol. I/ Issue I/April-June, 2010/9-16 or may not be biodegradable (Courveur et al 1995 and 1988). The term nanoparticle is a collective name for nanospheres, metal nanoparticles and nanocapsules. Polymeric composition, hydrophobicity (Christian Wischkel and Schwendeman 2008), surface charge and biodegradation profile of the nanoparticles, any adjuvant substances, and the associated drug (molecular weight, charge, localization in the nanospheres by adsorption or incorporation) have a great influence on the drug absorption, biodistribution pattern and elimination. Nanoparticles have been prepared most frequently by three methods: dispersion of preformed polymers, polymerization of monomers and ionic gelation or coacervation of hydrophilic polymers (Mohanraj and Chen 2006). Colloidal gold has been safely used for over 70 years to treat rheumatoid arthritis. Targeted drug therapy is a promising, fast growing drug delivery application which safely (Gang Han et al 2007), efficiently and effectively addresses specific diseases while minimizing toxicities. Gold nanoparticles have demonstrated remarkable properties, displaying nontoxicity to human cells and biocompatibility (Hainfeld et al 2004, Rena and Chow 2003, Gu et al 2003). Coating nanometer sized colloidal gold particles completely alters the biodistribution of these particles, allowing them to find solid tumors and deliver therapeutic payloads while bypassing normal cells thus minimizing the side effects. Researchers have come up with a unique method of detecting cancer in which gold nanoparticles that were bound to a specific antibody displayed a 600 percent greater affinity for cancer cells than for noncancerous cells. The change in the absorption spectrum of the gold nanoparticles (Thomas and Kamat 2000) allows the differentiation between cancer cells and noncancerous cells. Hence, the gold nanoparticles are useful for cancer detection and remission of cancer. Hence gold nanoparticles were utilized for sustained release of drugs. Cellulose esters have played a vital role in the development of modern drug delivery technology (Edgar et al 2007). They possess properties which suit the needs of pharmaceutical applications for drug delivery systems which satisfies the patient needs. Ethyl cellulose is a International Journal of Advanced Engineering Technology IJAET/Vol. I/ Issue I/April-June, 2010/9-16 biodegradable polymer used in the preparation of microspheres (Ghorab et al 1990). It is a water insoluble polymer used in the preparation of microcapsules for sustained release applications (Itoh et al 1979, Desai et al 2003, Riikka Maki et al 2006). A novel drug delivery system containing poly(lactic-co-glycolic acid) as the main bioerodible component used in the bulk layer and ethyl cellulose applied as a matrix polymer enables a diffusion-controlled release. (Bromberg et al 2001). Hence an attempt was made to synthesize Poly lactic acid-co-ethyl cellulose copolymer for sustained release applications.