Chitosan-stavudine (d4T) conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5'-O-succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate (TPP) to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy (TEM), and their zeta potential, particle size, and polydispersity (size distribution) were measured by the dynamic light scattering (DLS) techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.
With a homogeneous distribution of hydroxyapatite (HAP) crystals in polymer matrix, composite scaffolds chitosan/ HAP and chitosan/collagen/HAP were fabricated in the study. XRD, SEM and EDX were used to characterize their components and structure, in vitro cell culture and in vivo animal tests were used to evaluate their biocompatibility. HAP crystals with rod-like shape embeded in chitosan scaffold, while HAP fine-granules bond with collagen/chitosan scaffold compactly. A homogenous distribution of Ca and P elements both in chitosan/HAP scaffold and chitosan/collagen/HAP scaffold was defined by EDX pattern. The presence of collagen brought a more homogenous distribution of HAP due to its higher ability to induce HAP precipitation. The results of in vitro cell culture showed that the composite's biocompatibility was enhanced by the homogenous distribution of HAP. In vivo animal studies showed that the in vivo biodegradation was effectively improved by the addition of HAP and collagen, and was less influenced by the homogeneous distribution of HAP when compared with a concentrated distribution one. The composite scaffolds with a homogeneous HAP distribution would be excellent alternative scaffolds for bone tissue engineering.
