Bupivacaine (S75:R25) Loaded in Nanostructured Lipid Carriers: Factorial Design, HPLC Quantification Method and Physicochemical Stability Study

Author(s)

Rodrigues da Silva, Gustavo Henrique ^[1] ; de Morais Ribeiro, Ligia Nunes ^[1] ; Guilherme, Viviane Aparecida ^[1] ; de Castro, Simone Ramos ^[1] ; Breitkreitz, Marcia Cristina ^[2] ; de Paula, Eneida ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Chem, Dept Analyt Chem, Campinas, SP - Brazil

• Document type: Journal article
• Source: CURRENT DRUG DELIVERY; v. 15, n. 3, p. 388-396, 2018.
• Web of Science Citations: 0

Abstract

Background: Bupivacaine is the most used local anesthetic in surgical procedures, producing prolonged anesthesia. The major limiting factor for the clinical use of bupivacaine comes from its systemic toxicity. Nanostructured lipid carriers (NLC) are vehicles for sustained drug delivery that are able to minimize the toxicity and to increase the action time of lipophilic drugs. Methods: This work reports a 2(2) factorial design, which elucidates the role of the lipids mixture in the NLC, towards an optimized formulation. It also provides a new method for bupivacaine S75:R25 (BVCS75) quantification in NLC. Moreover, physicochemical stability studies on the prepared NLC formulations were carried out by monitoring particle size, polydispersity, Zeta potential and BVCS75 encapsulation efficiency for 90 days, at 25 degrees C. Results: The factorial design showed that the liquid lipid Capryol 90 (R) has a negative effect over particle size and PDI values while cetyl palmitate presented a positive effect in size. The analytical method was accurate, reproducible, specific and linear over the concentration range of 0.16-54.00 mu g.mL(-1) BVCS75 with limits of quantification and detection of 0.10 and 0.03 mu g.mL(-1), respectively. The validated method was used to quantify the BVCS75 encapsulation (55.5 +/- 2.8 %). Encapsulation did not affect the nanoparticles morphology (confirmed by Transmission Electron Microscopy), but increased their Zeta potential (from -15.7 to -37.0 mV). The NLC physical stability was maintained (particles: size < 170 nm, polydispersity <0.16, and number = 8.85 +/- 0.11 x 10(13) particles.mL(-1)) during storage. Conclusion: These results support further investigations on the use of BVCS75-in-NLC formulation for surgical anesthesia, aiming the development of a potent and less toxic nanostructured lipid carrier formulation for BVCS75. (AU)

• FAPESP's process: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants