4.5 Article

Design of polymeric nanoparticles for oral delivery of capreomycin peptide using double emulsion technique: Impact of stress conditions

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ELSEVIER
DOI: 10.1016/j.jddst.2022.103326

关键词

Capreomycin peptide; Double emulsion evaporation; Stress conditions; Chitosan; PLGA; Nanoparticles

资金

  1. King Saud University, Vice Deanship of Research Chairs, Kayyali Chair for Pharmaceutical Industries [FS-2021]

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Peptides are unstable under drastic conditions, but using polymeric nanoparticles as carriers for peptides in pharmaceutical field is highly desirable due to their stability in biological environment. This study used double emulsion solvent evaporation technique to formulate nanoparticles as carriers for capreomycin sulfate (CMS) peptide. Optimization of formulation factors allowed the production of polymeric nanoparticles with small particle sizes and high entrapment efficiencies. In vitro drug release experiments showed that PLGA NPs exhibited slower release compared to chitosan NPs.
Peptides are short polymers of amino acids that are unstable at drastic conditions including highly acidic or highly alkaline media, high temperature and high shear forces. Polymeric nanoparticles as carrier for peptides are the most desirable formulation in pharmaceutical field than other colloidal systems because of their stability in biological environment. Two different biodegradable polymers were chosen to formulate nanoparticles as carriers for capreomycin sulfate (CMS) peptide. Chitosan was selected as a water soluble polymer, while, poly (lactic-co-glycolic) acid (PLGA) polymer is soluble in organic solvents. Double emulsion solvent evaporation technique was used in the formulation of the nanoparticles. This method required applying of thermal, mechanical and chemical stresses that could have impact on peptide degradation that should be considered in the design of nanoparticles. Many formulation factors for polymeric nanoparticles optimization were tested including: probe sonication intensity and time, homogenization speed, pH of dispersion media, drug:polymer ratios, type and concentration of crosslinking agents and concentration of the stabilizer. Controlling these factors with monitoring of peptide degradation allowed to optimize polymeric nanoparticles having the smallest possible particle sizes (343.7-1656.5 nm) with the highest entrapment efficiencies (17.30-62.30%). The produced polymeric nanoparticles were tested for in vitro drug release in phosphate buffer pH 6.8. Different CMS release profiles were observed (15.52-72.44%) where PLGA NPs showed significant slower release compared with that of chitosan NPs.

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