title: Local anesthetic effects of bupivacaine loaded lipid-polymer hybrid nanoparticles: In vitro and in vivo evaluation.
abstract: OBJECTIVE
  There is a compelling need for prolonged local anesthetic that would be used for analgesia with a single administration. However, due to the low molecular weight of local anesthetics (LA) (lidocaine, bupivacaine, procaine, dibucaine, etc), they present fast systemic absorption.
  
  
  METHODS
  The aim of the present study was to develop and evaluate bupivacaine lipid-polymer hybrid nanoparticles (BVC LPNs), and compared with BVC loaded PLGA nanoparticles (BVC NPs). Their morphology, particle size, zeta potential and drug loading capacity were evaluated. In vitro release study, stability and cytotoxicity were studied. In vivo evaluation of anesthetic effects was performed on animal models.
  
  
  RESULTS
  A facile nanoprecipitation and self-assembly method was optimized to obtain BVC LPNs, composed of PLGA, lecithin and DSPE-PEG2000, of ∼175nm particle size. Compared to BVC NPs, BVC LPNs exhibited prolonged in vitro release in phosphate-buffered saline (pH=7.4). Further, BVC LPNs displayed enhanced in vitro stability in 10% FBS and lower cytotoxicity (the concentration of BVC ranging from 1.0μM to 20μM). In addition, BVC LPNs exhibited significantly prolonged analgesic duration.
  
  
  CONCLUSIONS
  These results demonstrate that the LPNs could function as promising drug delivery system for overcoming the drawbacks of poor stability and rapid drug leakage, and prolonging the anesthetic effect with slight toxicity.
authors.affiliation: Department of Anesthesiology, Anqiu People's Hospital, Anqiu 262100, Shandong Province, China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Ma
authors.affiliation: Delivery Room, People's Hospital of Anqiu, Anqiu 262100, Shandong Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan 250117, Shandong Province, China. Electronic address: huaixinxingsdpc@163.com.
authors.forename: Huaixin
authors.initials: H
authors.lastname: Xing
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, Shandong Province, China.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Weifang Medical University, Weifang 261042, Shandong Province, China.
authors.forename: Yingui
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Gynecological Tumor, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, Shandong Province, China.
authors.forename: Xiugui
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Anesthesiology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, Shandong Province, China.
authors.forename: Kaiguo
authors.initials: K
authors.lastname: Wang
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004355:Drug Stability; D019344:Lactic Acid / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D010147:Pain Measurement / Q000187:drug effects; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D012995:Solubility
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D008055:Lipids; D010714:Phosphatidylethanolamines; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D002045:Bupivacaine
keywords: Bupivacaine; Cytotoxicity; Lipid-polymer hybrid nanoparticles; Polymeric nanoparticles; Prolonged local anesthetic