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Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity
Juliana Damasceno Oliveira1, Lígia Nunes de Morais Ribeiro1, Gustavo Henrique Rodrigues da Silva1
1Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas - Unicamp, P.O. Box - 6109, CEP, Campinas, SP, 13083-862, Brazil.
Pharmaceutical Research
|October 12, 2018
Summary
Ionic gradient liposomes (IGL) encapsulate etidocaine (EDC) to reduce its toxicity and prolong release. This novel formulation enhances EDC
Area of Science:
- Pharmacology
- Materials Science
- Nanotechnology
Background:
- Etidocaine (EDC) is a long-acting local anesthetic with limited clinical use due to toxicity concerns.
- Liposomal drug delivery systems can improve anesthetic efficacy and safety profiles.
- Ionic gradient liposomes (IGL) offer enhanced drug loading and sustained release capabilities.
Purpose of the Study:
- To develop and characterize a novel liposomal formulation of etidocaine (EDC) using ionic gradient liposomes (IGL).
- To evaluate the in vitro release kinetics and cytotoxicity of the developed IGL-EDC formulation.
- To assess the potential of IGL-EDC for reintroducing etidocaine into clinical practice.
Main Methods:
- Validated a High-Performance Liquid Chromatography (HPLC) method for etidocaine quantification.
- Prepared large unilamellar vesicles (LUVs) using hydrogenated soy phosphatidylcholine:cholesterol with an ammonium sulfate gradient for EDC encapsulation.
- Characterized nanoparticles using Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), and Electron Paramagnetic Resonance (EPR).
- Assessed in vitro release kinetics and cytotoxicity against human fibroblasts.
Main Results:
- IGL-EDC nanoparticles exhibited a mean diameter of 172.3 ± 2.6 nm with low polydispersity (PDI=0.12 ± 0.01) and a particle concentration of 6.3 ± 0.5 × 10^12/mL.
- The formulation demonstrated a 40% encapsulation efficiency and sustained EDC release over approximately 24 hours.
- IGL-EDC significantly reduced the cytotoxicity of etidocaine to human fibroblasts compared to the free drug.
Conclusions:
- A novel etidocaine formulation using ionic gradient liposomes (IGL-EDC) was successfully developed.
- The IGL-EDC formulation promotes sustained drug release and mitigates etidocaine's cytotoxicity.
- This liposomal approach holds promise for the potential reintroduction of etidocaine into clinical applications.
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