Achieving long-term controlled drug delivery by using biodegradable polymeric nanoparticles
Long-term drug delivery has advantages over traditional drug delivery, including better patient compliance, increased effectiveness of drugs and reduction of side effects. A promising way to achieve long-term controlled drug delivery is to use drug-loaded biodegradable polymeric nanoparticles. A specific problem in using nanoparticles for controlled drug delivery is to control the duration of action and the rate and amount of drug released at any time. We have addressed this problem by using a system of a model hydrophobic drug, haloperidol encapsulated in a biodegradable polymer, poly(lactide-co-glycolide acid) (PLGA). We have developed emulsion-solvent evaporation methods for producing haloperidol-loaded PLGA nanoparticles with up to 2.5% (wt/wt. of polymer) drug content, in-vitro release duration of 13-40 days and less than 20% burst release. The free haloperidol is removed from the nanoparticle suspension using a novel solid phase extraction technique. The size of nanoparticles was effectively controlled in the range of 220-1000 nm by choosing appropriate preparation method and processing conditions, including polymer concentration in the organic phase and energy added. The drug content was controlled by increasing the drug-polymer interaction and decreasing drug diffusion into the aqueous phase. We have discovered that PLGA end groups have a strong influence on haloperidol incorporation efficiency and its release from PLGA nanoparticles. The drug incorporation efficiency with uncapped PLGA was three times that with capped PLGA. The in-vitro release profile of nanoparticles with uncapped PLGA had a longer release period and a lower initial burst as compared to capped PLGA. We established that the in-vitro release is predominantly diffusion controlled by comparing our experimental data with theoretical models. The release is strongly dependent on the size of particles and the polymer hydrophobicity. We have seen that coating the particles with chitosan prolongs the release and reduces the burst. The drug release profiles were tailored to achieve specific objectives in terms of release duration, rate of release, and release amount by simultaneously manipulating multiple parameters and properties.
Budhian, Avinash, "Achieving long-term controlled drug delivery by using biodegradable polymeric nanoparticles" (2006). Dissertations available from ProQuest. AAI3225435.