Entrapment Efficiency and Release Kinetics of Antihypertensive and Anticancer Drugs using Biodegradable Polymer Particles

Abstract

The work presented in this thesis enlightens the significance of biodegradable polymeric materials for their intended use as drug delivery carriers. Main emphasis has been given to the synthesis of polymeric nanoparticles (NPs) in the form of core@shell and hollow nanostructures by varying the nature of core, shell composition, their characterization and application in drug delivery. In order to improve the therapeutic efficacy of ramipril, an antihypertensive drug, a study has been carried out to ascertain the duration of its action. Ramipril loaded biodegradable nanoparticles of poly-D,L-lactide-co-glycolide (PLGA) were prepared by nanoprecipitation using tribloere stabilizer kolliphor P-188 (K P-188). Four different formulations F1 to F4 were prepared by altering the weight of K P-188: PLGA. Further, the core-shell morphology of poly- lactic /poly-lactic-co-glycolic acid- poly N-isopropylacrylamide nanocomposite was assessed to study the release kinetics of ramipril. In-vitro release study of the formulations at pH 5.3 in phosphate buffer indicated poly-lactic-co-glycolic acid to be more efficient than poly- lactic acid with a sustained release of 86% of ramipril from the polymer matrix within 24 hours. Also, chitosan hollow nanospheres were prepared using poly-D,L-lactide-co-glycolide as template by single emulsion method. The in-vitro release of ramipril of 86% and 73% was achieved in acetate (pH-3.3) and phosphate (pH-6.3) buffers respectively while only 48% of ramipril in Tris buffer (pH- 8.0) medium. Korsemeyer-Peppas model of drug release indicated the release of ramipril being swelling controlled. Apart from this surface modification using magnetic nanoparticles to enhance the ability of amphiphilic block polymers by increasing their surface properties was studied. In this study, Fe3O4 modified PLGA-PEG nanocomposite is prepared by double emulsion method. The effectiveness of prepared magnetically modified nanoparticles was determined by encapsulating methotrexate (anticancer drug) into the nanocomposite. The cytotoxic cell viability assay on SK-BR-3 (breast adinocarcinoma) cells showed that loaded methotrexate showed higher cell viability (17%) as compared to free methotrexate (29%) after 96h of incubation. Hence, biodegradable polymeric nanoparticles hold the potential to be used as drug delivery carriers in the future.