Formulation of PLGA Nanoparticles for Anticancer Drug-Doxorubicin and Sustained Release Studies of the Drug In Simulated Buffer Systems

AIMS : Since anticancer drugs lack specificity, are highly toxic and have to be administered for long durations, drug delivery systems seem promising for such treatments by modifying the bio-distribution and pharmacokinetics of the drug in vivo. Polymer based sustained release of these drugs from nanoparticles (NP) will lead to maintenance of drug levels within desirable range with much lower doses, reducing the toxicity, number of administrations and better patient compliance. Polylactic acid (PLA) and polyglycolic acid (PGA) copolymer, PLGA has been suitable because of its excellent biocompatibility and biodegradability Here, we report the studies done on encapsulation and in vitro release of the chemotherapeutic drug doxorubicin from poly(lactic-co-glycolic acid) nanoparticles under in vitro simulated conditions.

METHODS: Doxorubicin-loaded nanoparticles were prepared by double emulsion evaporation technique using dichloromethane as solvent and Polyvinyl alcohol (PVA) as a stabilizing agent. Concentration of PVA was found to influence the release characteristics, therefore 2, 3 and 4% PVA was used in the preparation of nanoparticles. Doxorubicin was estimated by flourimetry at λ_ex 470 nm; λ_em 585 nm using a standard curve of doxorubicin. In vitro sustained release studies have been done in various biologically simulated buffers.

RESULTS: Encapsulation of the drug was estimated ( by dissolving the particles in lysis buffer and estimation as explained below )and was found to vary from 5-10 ug/ mg of nanoparticle pellet. Release of doxorubicin at different pH could be observed till 10 days in a sustained fashion but fall in concentration after 5^thday onwards and maximum release could be observed on 4-5th day. Faster release was seen in 2% PVA and at a lower pH 4.5 as compared to pH 7.2  Data obtained shows the release of drug in a pH dependent manner.

DISCUSSION:

Double emulsion by sonication and use of PVA as coating agent at a conc of 3%  was found to encapsulate relatively high doxorubicin with  efficiency of encapsulation being 17 %. Accelerated release of drug at low pH may be due to faster degradation of polymer in acidic conditions.  Studies are being done to  determine more precisely the effects of variables on the release characteristics of the drug under in vitro conditions

CONCLUSION:

Nanoparticles formulated by  technique of double emulsion evaporation were found to be able to control the release of doxorubicin in a pH-dependent manner till 10 days with a maxima at day 5 in all pH studied.