Synthesis and characterizations of amphiphilic poly(L-lactide)-grafted chondroitin sulfate copolymer and its application as drug carrier.

In this investigation, new biodegradable brush-like amphiphilic copolymers were synthesized by ring opening polymerization. Poly(L-lactide) (PLLA) was grafted onto chondroitin sulfate (CS), which is one of the physiologically significant specific glycosaminoglycans (GAGs), using a tin octanoate [Sn(Oct)2] catalyst in DMSO. The hydroxyl groups of the chondroitin sulfate were used as initiating groups. These functional groups enable specific mucoadhesion or receptor recognition. The degree of substitution (DS), the degree of polymerization (DP) and the chondroitin sulfate content (from 1.1 to 15.4%) were analyzed by 1H NMR. The characteristics of these grafted copolymers, including the structure, the thermal properties and biodegradability, etc., were examined with respect to CS content. Meanwhile, the amphiphilic core (PLLA)-corona (CS) nanoparticles, with size smaller than 200 nm, was examined by dynamic light scattering (DLS). Zeta potential analysis exhibited the value in the range -18.3 to -49.4 mV. The morphologies of the nanoparticles were observed by field-emission scanning electron microscopy (FE-SEM). The nanoparticles with lower cytotoxicity were examined by MTT assay. Furthermore, the in vitro BSA release kinetics of those CSn-PLLA nanoparticles was also determined in this study.

Preparation of porous biodegradable poly(lactide-co-glycolide)/ hyaluronic acid blend scaffolds: characterization, in vitro cells culture and degradation behaviors.

A series of poly(lactide-co-glycolide) (PLGA)/ hyaluronic acid (HA) blend with different HA composition were used to fabricate scaffolds successfully. The pores of the three dimensional scaffold were prepared by particle leaching and freeze drying. The pore size was about 50-200 microm and the porosity was about 85%. The characterizations of the scaffold, such as mechanical properties, hydrophilicity and surface morphologies were determined. Mouse 3T3 fibroblast was directly seeded on the scaffolds. The cell adhesion efficiency, cell morphology observed by scanning electron microscopy (SEM) and the degradation behavior of the blend scaffold were evaluated. In summary, the results show that the adhesion efficiency of cells on the PLGA/HA blend scaffold is higher than that on the PLGA scaffold. Moreover, the incorporation of HA in PLGA not only helps to increase the cell affinity but also tends to lead the water and nutrient into the scaffold easily.

Biomimetic porous scaffolds made from poly(L-lactide)-g-chondroitin sulfate blend with poly(L-lactide) for cartilage tissue engineering.

A novel biodegradable graft copolymer chondroitin sulfate-grafted poly(L-lactide) (CS-PLLA) was synthesized. The graft copolymer was blended with PLLA to form biomimetic porous scaffolds. Natural CS was introduced into the polyester matrix to promote the proliferation of cells. Three-dimensional spongelike scaffolds were fabricated by a combination of salt leaching and solvent casting methods. The morphology of the scaffolds was observed with scanning electron microscopy with an average pore size between 50 and 250 microm, and its porosity was high (>85%). Compression analysis indicated that the mechanical properties of the scaffold were adequate to support the proliferation of cells. The hydrophilicity increased with an increase in the copolymer content in the blend, as determined by measuring the contact angle. Hematoxylin and eosin, Masson, and Safranin-O staining showed that cells formed a chondro tissue gradually. Histological results revealed that abundant cartilaginous matrixes surrounded spherical chondrocytes in the center of the explants. Chondrocytes cultured in this extracellular-matrix-like scaffold maintained a round morphology phenotype, characterized by a significant quantity of extracellular matrixes of sulfated glycosaminoglycans and collagens. Additionally, phenotypic gene expression (reverse transcriptase-polymerase chain reaction) indicated that chondrocytes expressed transcripts that encoded type II collagen and aggrecan and generated sulfated glycosaminoglycans.

Preparation of amphiphilic poly(L-lactide)-graft-chondroitin sulfate copolymer self-aggregates and its aggregation behavior.

Novel polymeric amphiphilic copolymers were synthesized using chondroitin sulfate (CS) as a hydrophilic segment and poly(L-lactide) (PLLA) as a hydrophobic segment. Micelles of those copolymers were formed in an aqueous phase and were characterized by 1H NMR spectra, fluorescence techniques, dynamic light scattering (DLS), atomic force microscopy (AFM), and confocal microscopy. Their critical aggregation concentrations (CAC) are in the range of 0.0043-0.0091 mg/mL at 25 degrees C. The partition equilibrium constants, Kv, of the pyrene probe in the aqueous solution were from 3.65 x 10(5) to 1.41 x 10(6) at 25 degrees C. The mean diameters of the micelles were below 200 nm, and their sizes were narrowly distributed. The AFM images revealed that the self-aggregates were spherical. Additionally, the CSn-PLLA micelles can efficiently transport within the cells via endocytosis as observed from confocal microscopy.