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Optimization and Characterization of Low-Molecular-Weight Chitosan-Coated Baicalin mPEG-PLGA Nanoparticles for the
Nan Li1,2, Zhiyue Zhao1,2, Hongfei Ma1,2
1State Key Laboratory of Component Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Abstract:
The present study was to evaluate the potential effectiveness of low-molecular-weight chitosan-coated baicalin methoxy poly(ethylene glycol)-poly(d,l-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (BA LCH NPs) for the treatment of cataract. mPEG-PLGA NPs were optimized by the Box-Behnken design and the central composite design based on the encapsulation efficiency and drug loading. Then, the BA LCH NPs were characterized based on morphology, particle size, and zeta potentials. The analytical data of differential scanning calorimetry, X-ray diffraction, and transmission electron microscopy depicted the drug excipient compatibility. In vitro, we evaluated cell viability, cellular uptake, potential ocular irritation, transcorneal permeability, and the precorneal retention of BA LCH NPs. In vivo, the chronic selenium cataract model was selected to assess the therapeutic effect of BA LCH NPs. The size of BA LCH NPs was within the range from 148 to 219 nm and the zeta potential was 19-25 mV. Cellular uptake results showed that the fluorescence intensity of the preparations in each group increased with time, and the fluorescence intensity of the LCH NP group was significantly higher than that of the solution group. The optimized BA LCH NPs improved precorneal residence time without causing eye irritation and also showed a sustained release of BA through the cornea for effective management of cataract. Also, fluorescence tracking on the rabbit cornea showed increased corneal retention of the LCH NPs. In addition, the results of therapeutic efficacy demonstrated that BA LCH NPs can significantly reduce the content of malondialdehyde and enhanced the activities of catalase, superoxide dismutase, and glutathione peroxidase, which was comparable to positive control and better than the BA solution group. Thus, it can be inferred that the BA LCH NPs are a promising drug delivery system for enhancing the ophthalmic administration of BA to the posterior segment of the eye and improving cataract symptoms.
