Pengju Ma1, Ting Li2, Huaixin Xing3, Suzhen Wang4, Yingui Sun5, Xiugui Sheng6, Kaiguo Wang7. 1. Department of Anesthesiology, Anqiu People's Hospital, Anqiu 262100, Shandong Province, China. 2. Delivery Room, People's Hospital of Anqiu, Anqiu 262100, Shandong Province, China. 3. 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. 4. Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, Shandong Province, China. 5. Department of Anesthesiology, Weifang Medical University, Weifang 261042, Shandong Province, China. 6. Department of Gynecological Tumor, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, Shandong Province, China. 7. Department of Anesthesiology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, Shandong Province, China.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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 bupivacainelipid-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. CONCLUSION: 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: Hitesh Chopra; Shabana Bibi; Rajat Goyal; Rupesh K Gautam; Rashmi Trivedi; Tarun Kumar Upadhyay; Mohd Hasan Mujahid; Mohammad Ajmal Shah; Muhammad Haris; Kartik Bhairu Khot; Gopika Gopan; Inderbir Singh; Jin Kyu Kim; Jobin Jose; Mohamed M Abdel-Daim; Fahad A Alhumaydhi; Talha Bin Emran; Bonglee Kim Journal: Front Oncol Date: 2022-07-12 Impact factor: 5.738