(283d) Potential Pharmaceutical Applications of Uniform-Sized Chitosan Micro/Nanospheres with Autofluorescent Property

  Chitosan has been adopted to have potential application in pharmaceutical science due to its outstanding properties of nontoxicity, biocompatibility, biodegradability, mucus-adhesion, and low cost. To cater to specific clinical requirements, we developed a series of novel chitosan-based mciro/nanospheres and testified their potenials in pharmaceutical applications.

  First, uniform-sized chitosan microspheres were prepared by porous membrane emulsification technique. These microspheres were found to be autofluorescent due to the crosslinking reaction. Their uniform size and autofluorescent property significantly facilitated our following studies.

  When microspheres were used as a drug carrier, their particle size highly correlated to subsequent transportation and metabolism in vivo. These microspheres with different size (2.1 μm, 7.2 μm, and 12.5 μm) exhibited distinguishing fates in bioadhesion, absorption and distribution, while the biodegradation also varied due to the different RES (reticuloendothelial system) locations.

  The demands on drug release behavior vary from case to case in clinical therapy. To solve this problem, we developed a series of novel chitosan microspheres, which could exhibit different release profiles. The tunable ability of structural properties, such as surface charge, cavity size, and wall porosity, enabled the modification of these microspheres to cater to specific requirements in clinic.

  Having revealed the influences of particle size and structure properties, we next used hollow-porous chitosan microspheres for oral administration of insulin. The hollow structure could conserve the bioactivity of encapsulated insulin, the quaternized group in matrix could decrease drug leakage by steric hindrance and enhance bioadhesive ability by electrostatic interaction, and the wall porosity could promote the insulin release. As expected, in vivo evaluation saw an optimal reduction in blood glucose level and powerful therapeutic effects after treatment with as-designed microspheres.

 We also used premix membrane emulsification technique to prepare chitosan (CS) and its derivative N-trimethyl chitosan chloride (TMC) nanoparticles (NPs) and testified their feasibility as carrier for insoluble anticancer drug paclitaxel (PTX). Both NPs displayed a narrow size distribution (150-200 nm), a high encapsulation efficiency (>80%), and a relatively high loading content (>30%). PTX could be well distributed in the NPs through an in-situ crystallization process. PTX-TMC NPs could be more readily taken up by LLC (Lewis Lung Cancer) cells due to the larger amount of positive charge on the surface of TMC NPs, thus leading to a better cytotoxicity than PTX-CS NPs and free drug (Taxol®). Moreover, PTX-TMC NPs could be absorbed more effectively by the gastrointestinal after orally administrated to LLC tumor-bearing C57/BL6 mice, accumulated in tumor tissue to a larger extent, exhibited greater tumor growth inhibition effect, and caused lower side effects than PTX-CS NPs and Taxol^®.

  All these results strongly supported that these uniform-sized autofluorescent chitosan micro/nanospheres hold great potentials for oral delivery of protein drugs and anticancer chemotherapy.