Natural lipids-based NLC containing lidocaine: from pre-formulation to in vivo studies

• Published in: European journal of pharmaceutical sciences Vol. 106; pp. 102 - 112
• Main Authors: Ribeiro, Lígia N.M., Breitkreitz, Márcia C., Guilherme, Viviane A., da Silva, Gustavo H.R., Couto, Verônica M., Castro, Simone R., de Paula, Bárbara O., Machado, Daisy, de Paula, Eneida
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30-08-2017
• Subjects: Animals; Beeswax; Chemistry, Pharmaceutical - methods; Drug Carriers - chemistry; Drug Liberation; Drug Stability; Excipients - chemistry; Humans; Lidocaine - administration & dosage; Lidocaine - chemistry; Lidocaine - pharmacokinetics; Lipids - chemistry; Male; Mice, Inbred BALB C; Nanoparticles - chemistry; Nanostructured lipid carriers; Particle Size; Plant Oils - chemistry; Poloxamer - chemistry; Surface Properties; Vegetable fats; Vegetable oils; Waxes - chemistry; Zebrafish; Nanostructured lipid carriers; Vegetable oils; Vegetable fats; Beeswax
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2017.05.060

In a nanotechnological approach we have investigated the use of natural lipids in the preparation of nanostructured lipid carriers (NLC). Three different NLC composed of copaiba oil and beeswax, sweet almond oil and shea butter, and sesame oil and cocoa butter as structural matrices were optimized using factorial analysis; Pluronic® 68 and lidocaine (LDC) were used as the colloidal stabilizer and model encapsulated drug, respectively. The optimal formulations were characterized by different techniques (IR-ATR, DSC, and TEM), and their safety and efficacy were also tested. These nanocarriers were able to upload high amounts of the anesthetic with a sustained in vitro release profile for 24h. The physicochemical stability in terms of size (nm), PDI, zeta potential (mV), pH, nanoparticle concentration (particles/mL), and visual inspection was followed during 12months of storage at 25°C. The formulations exhibited excellent structural properties and stability. They proved to be nontoxic in vitro (cell viability tests with Balb/c 3T3 fibroblasts) and significantly improved the in vivo effects of LDC, over the heart rate of zebra fish larvae and in the blockage of sciatic nerve in mice. The results from this study support that the proper combination of natural excipients is promising in DDS, taking advantage of the biocompatibility, low cost, and diversity of lipids.
Illustrative representation of a NLC prepared with natural lipids. Three different optimized NLC systems for lidocaine delivery were prepared, using copaiba oil and beeswax, sweet almond oil and shea butter, or sesame oil and cocoa butter as the lipid matrix, plus Pluronic® 68 as surfactant. The systems were evaluated from pre-formulation to in vivo studies and the most prominent results are highlighted. [Display omitted]