title: Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel.
abstract: We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-release platform (90% release after 24 h), bupivacaine hydrochloride was incorporated into collagen/poly(γ-glutamic acid) hydrogel, which exhibited gel formation at body temperature. PLGA microparticles (diameter 1-3 μm) containing bupivacaine base showed a very slow release of bupivacaine (95% after 240 h), whereas PLGA nanoparticles (124 ± 30 nm) containing bupivacaine base demonstrated an intermediate release rate (95% after 160 h). By changing the relative composition ratio between the 3 components in these injectable composite hydrogels, the release of bupivacaine could be easily controlled from very rapid (within 1 day) to very delayed (up to 9 days). The experimental results on the release data (cumulative release, time point release, average release rate) were coincident with the release profile generated by computer simulation. These injectable composite hydrogels with systematically tunable mixing ratios are expected to serve as a promising technology for the on-demand release of bupivacaine in pain management.
authors: SKKU Advanced Institute of Nanotechnology, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Van Vuong
authors: VV
authors: Dinh
authors: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Yun-Suhk
authors: YS
authors: Suh
authors: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Han-Kwang
authors: HK
authors: Yang
authors: SKKU Advanced Institute of Nanotechnology, Sungkyunkwan University, Suwon, Republic of Korea. Electronic address: yongtaik@skku.edu.
authors: Yong Taik
authors: YT
authors: Lim
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry; D002045:Bupivacaine / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004333:Drug Administration Routes; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002045:Bupivacaine
keywords: controlled release; hydrogels; microparticles; nanoparticles; simulations