Production of haloperidol loaded PLGA nanoparticles for extended controlled drug release of haloperidol

This study developed an emulsion-solvent evaporation method for producing haloperidol-loaded PLGA nanoparticles with up to 2% (wt/wt. of polymer) drug content, in vitro release duration of over 13 days and less than 20% burst release. The free haloperidol is removed from the nanoparticle suspension using a novel solid phase extraction technique. This leads to a more accurate determination of drug incorporation efficiency than the typical washing methods. It was discovered that PLGA end groups have a strong influence on haloperidol incorporation efficiency and its release from PLGA nanoparticles. The hydroxyl-terminated PLGA (uncapped) nanoparticles have a drug incorporation efficiency of more than 30% as compared to only 10% with methyl-terminated PLGA (capped) nanoparticles. The in vitro release profile of nanoparticles with uncapped PLGA has a longer release period and a lower initial burst as compared to capped PLGA. By varying other processing and materials parameters, the size, haloperidol incorporation and haloperidol release of the haloperidol-loaded PLGA nanoparticles were controlled

Controlling the \u3cem\u3eIn Vitro\u3c/em\u3e Release Profiles for a System of Haloperidol-Loaded PLGA

We have used a systematic methodology to tailor the in vitro drug release profiles for a system of PLGA/PLA nanoparticles encapsulating a hydrophobic drug, haloperidol. We applied our previously developed sonication and homogenization methods to produce haloperidol-loaded PLGA/PLA nanoparticles with 200–1000 nm diameters and 0.2–2.5% drug content. The three important properties affecting release behavior were identified as: polymer hydrophobicity, particle size and particle coating. Increasing the polymer hydrophobicity reduces the initial burst and extends the period of release. Increasing the particle size reduces the initial burst and increases the rate of release. It was also shown that coating the particles with chitosan significantly reduces the initial burst without affecting other parts of the release profile. Various combinations of the above three properties were used to achieve in vitro release of drug over a period of 8, 25 and \u3e40 days, with initial burst \u3c25% and a steady release rate over the entire period of release. Polymer molecular weight and particle drug content were inconsequential for drug release in this system. Experimental in vitro drug release data were fitted with available mathematical models in literature to establish that the mechanism of drug release is predominantly diffusion controlled. The average value of drug diffusivities for PLGA and PLA nanoparticles was calculated and its variation with particle size was established

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

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