Encapsulation of Local Anesthetic Bupivacaine in Biodegradable Poly(DL‐lactide‐co‐glycolide) Nanospheres: Factorial Design, Characterization and Cytotoxicity Studies

Abstract

Summary: Local anesthetic agents cause temporary blockade of nerve impulses productiong insensitivity to painful stimuli in the area supplied by that nerve. Bupivacaine (BVC) is an amide‐type local anesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. In this study, we prepared and characterized nanosphere formulations containing BVC. To achieve these goals, BVC loaded poly(DL‐lactide‐co‐glycolide) (PLGA) nanospheres (NS) were prepared by nanopreciptation and characterized with regard to size distribution, drug loading and cytotoxicity assays. The 23‐1 factorial experimental design was used to study the influence of three different independent variables on nanoparticle drug loading. BVC was assayed by HPLC, the particle size and zeta potential were determined by dynamic light scattering. BVC was determined using a combined ultrafiltration‐centrifugation technique. The results of optimized formulations showed a narrow size distribution with a polydispersivity of 0.05%, an average diameter of 236.7 ± 2.6 nm and the zeta potential −2.93 ± 1,10 mV. In toxicity studies with fibroblast 3T3 cells, BVC loaded‐PLGA‐NS increased cell viability, in comparison with the effect produced by free BVC. In this way, BVC‐loaded PLGA‐NS decreased BVC toxicity. The development of BVC formulations in carriers such as nanospheres could offer the possibility of controlling drug delivery in biological systems, prolonging the anesthetic effect and reducing toxicity.

From micro- to nanostructured implantable device for local anesthetic delivery

“…[94][95][96][97][98][99] The first technique consists of making a solution (oily phase) in which the polymer and the drug are dissolved in organic solvents (typically methylene chloride or chloroform). The organic solution is subsequently poured into an aqueous solution (which often contains PVA, which acts as the emulsifier) and the suspension is vortexed.…”

Preparation of Hybrid Fe3O4/Poly(lactic‐co‐glycolic acid) (PLGA) Particles by Emulsion and Evaporation Method. Optimization of the Experimental Parameters

“…During the last years, poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and more specifically its co‐polymers poly(lactic‐ co ‐glycolic acid) (PLGA) have been investigated for applications in controlled drug delivery due to their biocompatibility and their biodegradability …”

Análise funcional do bloqueio ciático em ratos com lidocaína associada à hialuronidase em complexação com hidroxipropil - ß-ciclodextrina e citotoxicidade

“…(Modificado de Misal et al, 2013) Atualmente, associado a anestésicos locais encontramos os seguintes sistemas de liberação lenta: lipossomas, biopolímeros (micro/nanocápsulas e micro/nanoesferas) (Hughes, 2005;Moraes et al, 2009), Xybrex (matriz contendo lidocaína 16%) (Wang et al, 2011) e as ciclodextrinas (Cortes, 1999;Kim et al, 2013) que são as nanopartículas utilizadas neste estudo, devido à possibilidade de da administração pela via parenteral de um de seus subtipos (HP-β-CD) (Shipton, 2012).…”