ABSTRACT
Star-shaped poly(epsilon-caprolactone) oligomers functionalized with succinic anhydride were used as prepolymers to prepare photocrosslinked poly(ester anhydride) to evaluate their in vivo drug delivery functionality and biocompatibility. Thus, in this work, erosion, drug release and safety of the photocrosslinked poly(ester anhydride) were examined in vitro and in vivo. A small water-soluble drug, propranolol HCl (M(w) 296 g/mol, solubility 50 mg/ml), was used as the model drug in an evaluation of the erosion controlled release. Drug-free and drug-loaded (10-60% w/w) poly(ester anhydride) discoids eroded in vitro (pH 7.4 buffer, +37 degrees C) linearly within 24-48 h. A strong correlation between the polymer erosion and the linear drug release in vitro was observed, indicating that the release had been controlled by the erosion of the polymer. Similarly, in vivo studies (s.c. implantation of discoids in rats) indicated that surface erosion controlled drug release from the discoids (drug loading 40% w/w). Oligomers did not decrease cell viability in vitro and the implanted discoids (s.c., rats) did not evoke any cytokine activity in vivo. In summary, surface erosion controlled drug release and the safety of photocrosslinked poly(ester anhydride) were demonstrated in this study.
Subject(s)
Biocompatible Materials/chemistry , Delayed-Action Preparations/chemistry , Polyesters/chemistry , Propranolol/administration & dosage , Animals , Cell Line , Cell Survival , Humans , Male , Photochemistry , Rats , Rats, Wistar , Surface PropertiesABSTRACT
A series of elastic polymer and composite scaffolds for bone tissue engineering applications were designed. Two crosslinked copolymer matrices with 90/10 and 30/70 mol % of epsilon-caprolactone (CL) and D,L-lactide (DLLA) were prepared with porosities from 45 to 85 vol % and their mechanical and degradation properties were tested. Corresponding composite scaffolds with 20-50 wt % of particulate bioactive glass (BAG) were also characterized. Compressive modulus of polymer scaffolds ranged from 190+/-10 to 900+/-90 kPa. Lactide rich scaffolds absorbed up to 290 wt % of water in 4 weeks and mainly lost their mechanical properties. Caprolactone rich scaffolds absorbed no more than 110 wt % of water in 12 weeks and kept their mechanical integrity. Polymer and composite scaffolds prepared with P(CL/DLLA 90/10) matrix and 60 vol % porosity were further analyzed in simulated body fluid and in osteoblast culture. Cell growth was compromised inside the 2 mm thick three-dimensional scaffold specimens as a static culture model was used. However, composite scaffolds with BAG showed increased osteoblast adhesion and mineralization when compared to neat polymer scaffolds.
Subject(s)
Bone Substitutes , Glass , Polyesters , Tissue Engineering/methods , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Biomarkers/metabolism , Body Fluids/chemistry , Bone Regeneration , Bone Substitutes/chemical synthesis , Bone Substitutes/chemistry , Bone Substitutes/metabolism , Cells, Cultured , Cross-Linking Reagents/chemistry , Glass/chemistry , Materials Testing , Osteoblasts/cytology , Osteoblasts/metabolism , Polyesters/chemical synthesis , Polyesters/chemistry , Polyesters/metabolism , Porosity , Surface PropertiesABSTRACT
In this study the properties of DL-lactide (DL-LA) copolymers with 5, 10, 15, 20, and 30 wt % (in feed) of epsilon-caprolactone (epsilon-CL) polymerized with stannous(II)octoate (SnOct) as catalyst and glycerol, laurylalcohol, or pentaerythritol as initiator were investigated. Thermal studies showed that the addition of 5 wt % (in feed) of epsilon-CL to the P(CL/DL-LA) copolymer decreased the Tg by about 5 degrees C. Hydrolysis tests were carried out for copolymers with 20 and 30 wt % (in feed) of epsilon-CL to study the degradation rate. Molecular weights decreased dramatically during the first week of hydrolysis, with mass losses occuring a few weeks later. The influence of glycerol and pentaerythritol as initiators, and the influence of epsilon-CL content on stress-strain behavior, tension set, and rheologic properties of the P(CL/DL-LA) copolymers were also investigated. The tensile testing of P(CL/DL-LA) copolymers containing 5, 10, 15, 20 wt % (in feed) of epsilon-CL showed that the properties of copolymers varied from hard and brittle to rubbery. The permanence of elastic properties was investigated with tension set measurements. These studies showed that copolymers crept remarkably under stress. The viscosity and elasticity of P(CL/DL-LA) copolymers at 120 degrees C were investigated using rheology studies.
