ABSTRACT
Objective To construct a novel thiolated chitosan modified poly(lactide-co-ε-caprolactone)-d-α-tocopheryl polyethylene glycol 1 000 succinate (PLA-PCL-TPGS) nanoparticle,and investigate the feasibility of its use as an oral carrier for lung cancer chemotherapy.Methods The PLA-PCL-TPGS random copolymer was synthesized and characterized.Then three types of nanoparticles from commercial PCL and PLA-PCL-TPGS random copolymer were prepared for oral carrier of paclitaxel,including 5％ thiolated chitosan-modified PCL nanoparticles (CNPs),unmodified PLA-PCL-TPGS nanoparticles (UNPs),and 5％ thiolated chitosan-modified PLA-PCL-TPGS nanoparticles (TNPs).The prepared nanoparticles were characterized in terms of size,Zeta potential,morphology,drug loading and encapsulation efficiency.The in vitro drug release profiles and cellular uptake of the nanoparticles by human lung cancer cell lines A549 cells were investigated,and cytotoxicity against A549 cells was also evaluated.The evened sac method was used for the measurement of transportation of paclitaxel across the intestine barrier.Results The field emission scanning electron microscopy results showed that the three types of paclitaxel-loaded nanoparticles were spherical with a diameter about 200 nm.The surface charge of PLA-PCL-TPGS nanoparticles was reversed from negative to positive charge after thiolated chitosan modification.The UNPs and TNPs achieved higher drug loading,encapsulation efficiency and drug release after 32 d than CNP (all P＜0.05).The TNPs had significantly higher cell uptake efficiency than that of CNPs and UNPs (all P＜0.05).In vitro cell viability studies showed advantages of TNPs over a clinically available paclitaxel injection in terms of cytotoxicity against A549 cells.Ex vivo absorption studies revealed that the TNPs can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein.Conclusion PLA-PCL-TPGS nanoparticles modified by thiolated chitosan can enhance the cellular uptake and cytotoxicity,which reveals a potential application for oral chemotherapy of lung cancer.
ABSTRACT
@#Ophthalmic solution of organic-inorganic layered double hydroxides hybrid nanocomposites based on layered double hydroxides(LDH)intercalated with pirenoxine sodium(PRN)and chitosan-glutathione(CG)was prepared, characterized and evaluated using rabbit precorneal retention. Mg-Al-PRN-LDH, Zn-Al-PRN-LDH and CG-PRN-LDH were synthesized by co-precipitation. The nanocomposites were characterized by laser particle sizer, powder X-ray diffraction(X-RD), fourier transform infrared spectra(FTIR)and transmission electron micrographs(TEM). The release of PRN from Mg-Al-PRN-LDH, Zn-Al-PRN-LDH, and CG-PRN-LDH nanocomposites and API in artificial tear was compared. Based on in vivo precorneal retention studies, PRN-LDH and CG-PRN-LDH nanocomposite dispersions showed significantly higher AUC(3. 72-, 7. 59-folds)and MRT(2. 18-, 2. 60-folds)than that of the commercial eye drops group. Organic-inorganic layered double hydroxides hybrid nanocomposites CG-PRN-LDH dispersions could remarkably improve precorneal retention of PRN.
ABSTRACT
METHODS: The pH-sensitive thiolated chitosan nanoparticles were prepared by ionic cross-linking reaction and characterized for the shape, particle size, Zeta potential, drug entrapment efficiency and loading capacity. In vitro release of low molecular weight heparin from the prepared nanoparticles was evaluated in 0.1 mol•L-1 HCl solution and phosphate buffered saline (PBS) at pH 6.8 using the dialysis method. The intestinal permeability was estimated utilizing Franz diffusion cell system.