Investigation On Biodegradable Polymeric Microspheres

With the development of biopharmaceuticals, the traditional drug delivery systems have several inherent problems. So many new and advanced drug deliverys with different functions occurred. In the study, we investigated several biodegradable carriers for drug controlled release system by different fabrication methods.Firstly, the core-shell biodegradable microspheres loading human serum albumin (HSA) and paracetamol were fabricated with a hydrophilic alginic acid (ALG) shell and a hydrophobic poly(D,L-lactide-co-glycolide) (PLGA) core. The two model drugs, HSA and paracetamol, were entrapped in the shell and core, respectively. These microspheres were characterized in terms of morphology, mean size and size distribution, drug loading efficiency, in vitro degradation and drugs release. The morphology of the microspheres was observed with scanning electron microscope (SEM), optical microscopy (OM) and transmission electron microscope (TEM). These photos revealed directly that the microspheres possessed core-shell structure. The degradation and drug release results showed that the microspheres have different feature on the degradation and drug release. The distinct double-walled structure of the microspheres would make an interesting device for exact controlled delivery of therapeutic agents at different stages.Secondly, PELA copolymers with different weight ratios of polyethylene glycol (PEG) were used as drug carriers in the study. Fluorescein isothiocyanate (FITC) as a fluorescent marker were entrapped. The size and morphology of the particles were observed with scanning electron microscope (SEM), atomic force microscope (AFM) and laser diffraction particle size analyzer (LDPSA). The purpose of the present work was mainly to investigate the cytotoxicity and the process of endocytosis of PELA particles with different contents of PEG and variable particle size using rat osteoblasts (OBs). The endocytosis was observed through a light microscope and a fluorescence microscope, and moreover, their intracellular uptake and retention were determined quantitatively using fluorescence spectrophotometer (FSP). The results showed that with content of PEG in PELA increased, the endocytosis of nanoparticles in osteoblasts was to reduce.Finally, biodegradable chitosan (CS) hollow nanospheres have been fabricated by employing uniform PELA nanoparticles as templates. The chitosan was adsorbed onto the surface of the PELA templates with layer by layer self-assemble method through the electrostatic interaction between the sulphuric acid groups (from SDS) on the templates and the amino groups on the chitosan. Subsequently, the core-coated structure of CS-PELA nanospheres was obtained with the adsorbed chitosan layer being crosslinked with glutaraldehyde. After the removal of the templates, PELA cores, CS hollow nanospheres were achieved. The morphology of the PELA templates, the CS-PELA core-coated nanospheres and the hollow CS nanospheres was characterized with transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The mean size and size distribution of these nanospheres were also measured with dynamic light scattering (DLS). The hollow structure was identified by TEM, AFM and laser confocal scanning microscope (LCSM). The antitumor drug model, adriamycin, was adsorbed on/into the CS hollow nanospheres. The drug release behaviors from the CS hollow nanospheres were investigated in phosphate buffered solution (PBS) at pH 7.4 and acetate buffered solution (ABS) at pH 4.5, respectively, at 37℃, and in vitro tumor cell growth inhibition assay was also evaluated. The results indicated that the biodegradable hollow nanospheres possess great potential applications in drug controlled release system.