Preparation And Characterization Of Drug-loaded Microspheres Based On Star-shaped Poly (L-lactide) And Studies On Their In Vitro Release Behaviors

A considerable amount of research has been conducted on drug delivery based on biodegradable polymers since these systems exhibit improved efficacy, reduced toxicity, enhanced patient compliance, and convenience in comparison with conventional dosage forms. Among all the use of biodegradable nano- and microspheres devices are preferred from the point of view of the stability because they offer the possibility of modulation of the drug-release profile. In recent years, biodegradable poly(L-lactide)s (PLLA) and its copolymers with glycolide (PLGA) microspheres have been widely used in pharmaceutical field with their superior drug, protein, and gene delivery capacities and enhanced structural stability. However, the inherent hydrophobicity coupled with the high crystallinity of PLLA is one of the disadvantages that restrict its applications. Nowadays, the star-shaped poly(L-lactide)s (s-PLLA) have attracted much attention to utilize them as microspheres in biomedical fields due to their special three-dimensional structures compared with linear counterparts, such as smaller hydrodynamic radius, lower solution viscosity and peculiar morphologies. Therefore, in this article, s-PLLA was synthesized by ring-opening polymerization of L-lactide using erythritol, xylitol and sorbitol as an initiator, respectively. Then rifampicin (RIF) or bovine serum albumin (BSA) used as model drug were encapsulated within the microspheres of s-PLLA via emulsion solvent evaporation technique. The main contents of the research were expanded as follows:(1) Preparation and characterization of RIF-loaded microspheres based on the star-shaped poly(L-lactide)s with an erythritol coreA series of star-shaped poly(L-lactide)s (s-PLLA) were synthesized via ring-opening polymerization of L-lactide (LLA) using erythritol as initiator in the presence of stannous octoate as catalyst. The structure and thermal properties of s-PLLA were characterized by 1H NMR, GPC and DSC. Then RIF was used as a hydrophobic model drug. RIF-loaded s-PLLA microspheres were prepared using an oil-in-water (O/W) emulsion solvent evaporation method. SEM and size characterizations indicated that s-PLLA with high monomer/initiator molar ratios (s-PLLA98 and s-PLLA99) could form regular microspheres with smooth surface and had narrow size distributions, which held the drugs well. The XRD spectra of the RIF-loaded microspheres demonstrated that s-PLLA and RIF were both in their amorphous state after the encapsulation process, which might be caused by the impediment effect of each other. The in vitro release profiles of the RIF-loaded microspheres showed that the s-PLLA99 microspheres had low burst release, slow and controllable cumulative release rate and the release process follows the Baker-Lonsdale equation.(2) Preparation and characterization of RIF-loaded microspheres based on s-PLLA with a sorbitol core and studies on their in vitro release behaviorsThe s-PLLA was synthesized by ring-opening polymerization of L-lactide using sorbitol as an initiator in the presence of stannous octoate as catalyst. The structure and molecular weight (Mw) of s-PLLA was characterized with’H NMR,13C NMR, and GPC. Then RIF used as a model drug was encapsulated within the microspheres of s-PLLA via oil-in-water (O/W) emulsion/solvent evaporation technique. The morphology, drug encapsulation efficiency (EE), and in vitro release behavior of the prepared microspheres were studied in details. Results indicated that the average diameters of s-PLLA microspheres can be controlled between 8-20 μm by varying the copolymer’s concentration or Mw, and the EE of RIF was mainly determined by the concentration of s-PLLA. The in vitro study showed that the burst release behavior can be depressed by increasing the Mw of the s-PLLA.(3) Preparation and characterization of BSA-loaded microspheres based on s-PLLA with a xylitol core and studies on their in vitro release behaviorsThe s-PLLA was synthesized by ring-opening polymerization of L-lactide using xylitol as an initiator in the presence of stannous octoate as catalyst. The structure and molecular weight of s-PLLA were characterized with 1H NMR, 13C NMR, and GPC Then s-PLLA microspheres containing water-soluble BSA were prepared using a water-oil-water (W1/O/W2) emulsion solvent evaporation method. The drug encapsulation efficiency (EE), microspheres size and size distribution and the surface morphology, were characterized with UV, static light scattering particle size analyzer and SEM. The RIF in vitro release studies was analyzed by a UV-spectrophotometer assay, as well as the mathematical modeling of drug release models were applied to study the release profile of BSA from the s-PLLA microspheres. Results indicated that the average diameters of s-PLLA microspheres could be controlled between 7-15 μm by varying the s-PLLA’s concentration or Mw and drug encapsulation efficiency 10%-42%. Moreover, the cumulative release demonstrated that BSA-loaded microspheres prepared by high molecular weight of s-PLLA had a slow release behavior in PBS (pH=7.4) release medium and the release process follows the Baker-Lonsdale equation.