期刊
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
卷 61, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jddst.2020.102121
关键词
PLGA; Vitamin E TPGS; Box behnken design; Release kinetics; HET-CAM
The study optimized the preparation process of PLGA nanoparticles loaded with Ketomlac using response surface methodology, with results showing that the optimized formulation had small particle size, high ζ potential, and high encapsulation efficiency. It exhibited good performance in terms of release characteristics and corneal permeation, and also showed good safety for ocular application.
Topical ocular delivery of therapeutics are always a challenging arena in order to achieve high ocular bioavailability with safe administration. Ideal ocular delivery of drug required 4 P's that is Patient compliance, Prolong retention, Penetration to cornea and Prolong release of drug. In an attempt to achieve desired characteristics for ocular delivery, Ketomlac loaded PLGA nanoparticles were fabricated by double emulsification solvent evaporation method and optimized by employing response surface methodology (RSM) followed by statistical analysis. Results obtained by RSM were further validated for fitness in model by different checkpoint formulations. Vitamin E TPGS was selected as emulsifier, which acquires high emulsifying capability and high permeability character. Zeta-size study revealed that optimized formulation has mean particle size 142.8 +/- 11.7 nm, which was in agreement of TEM study and zeta potential was found -24.2 +/- 1.2 mV. Encapsulation efficiency was achieved 63.5 +/- 8.4%. Release profile was established by different mathematical modelling. It was observed that optimized formulation showed sustained release and followed by Korsmeyer-Peppas model. Corneal transport study showed enhanced drug permeation as compared to drug solution. HET-CAM test and histopathology studies revealed that optimized PLGA NPs was non-irritant and safe for ocular application.
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