ABSTRACT
Adaptation of cyclic brush polymer for drug delivery applications remains largely unexplored. Herein, cyclic brush copolymer of poly(2-hydroxyethyl methacrylate-g-poly(N-isopropylacrylamide-st-N-hydroxyethylacrylamide)) (cb-P(HEMA-g-P(NIPAAm-st-HEAAm))), comprising a cyclic core of PHEMA and thermosensitive brushes of statistical copolymer of P(NIPAAm-st-HEAAm), is designed and synthesized successfully via a graft-from approach using atom transfer free radical polymerization from a cyclic multimacroinitiator. The composition of the brush is optimized to endow the resulting cyclic brush copolymer with a lower critical solution temperature (LCST) slightly above the physiological temperature, but lower than the localized temperature of tumor tissue, which is suitable for the hyperthermia-triggered anticancer drug delivery. Critical aggregation concentration determination reveals better stability for the unimolecular nanoparticle formed by the cyclic brush copolymer than that formed by the bottlebrush analogue. The dramatically increased size with elevated temperatures from below to above the LCST confirms hyperthermia-induced aggregation for both formulations. Such structural destabilization promotes significantly the drug release at 40 °C. Most importantly, the drug-loaded cyclic brush copolymer shows enhanced in vitro cytotoxicity against HeLa cells than the bottlebrush counterpart. The better stability and higher therapeutic efficacy demonstrates that the thermosensitive cyclic brush copolymer is a better formulation than bottle brush copolymer for controlled drug release applications.
Subject(s)
Antineoplastic Agents/administration & dosage , Doxorubicin/administration & dosage , Drug Delivery Systems/methods , Polymers/chemistry , Temperature , Acrylic Resins/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Cell Survival/drug effects , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Drug Liberation , HeLa Cells , Humans , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Particle Size , Polyhydroxyethyl Methacrylate/chemistry , Polymers/chemical synthesisABSTRACT
OBJECTIVE: To present the treatment outcome for patients with displaced inferior pole patella fractures treated with anterior tension band wiring through cannulated screws. DESIGN: Case series. SETTING: Academic Level I trauma center. PATIENTS/PARTICIPANTS: During a 2-year period between January 2007 and December 2008, 10 consecutive patients (mean age, 59.8 years) with distal pole fractures of the patella (Orthopaedic Trauma Association 45.A.1) were prospectively enrolled in this study. INTERVENTION: All 10 patients underwent vertical skin exposure, fracture open reduction, and internal fixation by anterior tension band wiring through 4.0-mm cannulated screws. MAIN OUTCOME MEASUREMENTS: The range of motion, loss of fracture reduction, implant migration, material failure, soft tissue irritation, and Bostman score and Short Musculoskeletal Functional Assessment dysfunction score were primary outcome measures. RESULTS: There were three single-fragment fractures and seven comminuted fractures. With 1-year follow-up, all fractures healed clinically in an average of 8 weeks and radiographically on average by 12 weeks. The average range of knee motion arc was 122.5° (range, 95°-140°). Five patients have an average flexion lag of 17° (range, 10°-30°). No patient had loss of fracture reduction, implant migration, material failure, or soft tissue irritation. The average Bostman score was 28.7 out of 30 (range, 27-30), and average Short Musculoskeletal Functional Assessment dysfunction score was 24.1 out of 100 (range, 15-39). All 10 patients stated they were highly satisfied. CONCLUSION: Anterior tension band wiring through cannulated screws for displaced inferior pole patella fractures is a safe, simple, and reliable alternative treatment with minimal soft tissue irritation. Good functional results and recovery can be expected.
