Ceramic/polymer nanocomposites with tunable drug delivery capability at specific disease sites.
Pharmaceutical agents are often used to stimulate new bone formation for the treatment of bone injuries or diseases (such as osteoporosis). However, there are several problems associated with current orthopedic drug delivery methods. First, conventional systemic administration of pharmaceutical agents may not effectively reach targeted sites and, thus, they can cause nonspecific bone formation in areas not affected by injury or disease. Second, even if intentionally delivered or implanted locally to the damaged bone tissue, these agents tend to rapidly diffuse into adjacent tissues due to weak physical bonding to their drug carriers, which limits their potential to promote prolonged bone formation in targeted areas of bone disease. Therefore, in this study, biodegradable ceramic/polymer nanocomposites were explored as novel drug carriers for orthopedic applications to prolong local drug release and, thus, improve drug effectiveness at bone disease sites. Specifically, a bone morphogenetic protein (BMP-7) derived peptide (DIF-7c) was used as a model drug in this study and was first loaded onto nanocrystalline hydroxyapatite (nano-HA) by either covalent chemical attachment or physical adsorption. These drug-carrying nano-HA particles were then dispersed into a degradable polymer (poly-lactide-co-glycolide or PLGA) matrix to create an implantable system capable of long-term drug release. The aminophase silane covalent chemical immobilization process was utilized in this study. These nanocomposite-based drug delivery systems were then characterized for drug loading efficiency and in vitro drug release. Results demonstrated that DIF-7c was successfully immobilized onto nano-HA placed in PLGA. Moreover, a greater prolonged two-phase release profile (of more than 3 months) was achieved when using aminophase silane chemical immobilization to nano-HA particles. Since previous studies have demonstrated greater in vivo bone growth on nano- compared with micron-HA particles placed in rat calvaria, this study continued to demonstrate that ceramic/polymer nanocomposites are promising candidates as novel orthopedic materials to promote bone regeneration.
Division of Engineering, Brown University, 182 Hope Street, Providence, Rhode Island 02912, USA.
Huinan
H
Liu
Thomas J
TJ
Webster
D000818:Animals; D001565:Benzoates / Q000378:metabolism; D001847:Bone Diseases / Q000628:therapy*; D002516:Ceramics / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid / Q000494:pharmacology*; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011804:Quinolines / Q000378:metabolism; D051381:Rats
D001565:Benzoates; D004337:Drug Carriers; D010455:Peptides; D011804:Quinolines; C069617:3-(4-carboxybenzoyl)-2-quinolinecarboxaldehyde; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid