DEVELOPMENT AND CHARACTERIZATION OF DIBUCAINE-LOADED SOLID LIPID NANOPARTICLES BY HIGH-PRESSURE HOMOGENIZATION FOR ENHANCED LOCAL ANESTHETIC EFFICACY AND SAFETY

Pankaj Gill, Dr. Umesh Kumar*, Manju Rani, Km Ankush

ABSTRACT

Dibucaine (DBC), a highly potent amide-type local anesthetic, is limited in clinical use by poor aqueous solubility, rapid systemic absorption, and narrow therapeutic index, which increase risks of CNS and cardiovascular toxicity. This study aimed to develop and comprehensively characterize DBC-loaded solid lipid nanoparticles (SLNs) using high-pressure homogenization to achieve sustained release, enhanced local efficacy, and improved safety profile. SLNs were prepared with myristyl myristate (SLNM) or cetyl palmitate (SLNCP) as lipid matrices (5% w/v), stabilized by Pluronic F68 (1% w/v), and loaded with 0.5% w/v DBC. The formulations exhibited high encapsulation efficiency (92.4 ± 2.1% for SLNM; 89.7 ± 1.8% for SLNCP), nanoscale hydrodynamic diameters (148.7 ± 3.9 nm and 162.4 ± 4.1 nm, respectively), low polydispersity indices (<0.25), and strongly negative zeta potentials (–29.6 to –32.1 mV), remaining stable over 240 days at 4°C. Transmission electron microscopy confirmed spherical morphology with distinct core-shell architecture. Differential scanning calorimetry revealed reduced crystallinity (74–77%), while electron paramagnetic resonance demonstrated increased lipid fluidity upon DBC incorporation. In vitro release studies showed biphasic, sustained Fickian diffusion profiles (Weibull β < 0.75; Korsmeyer-Peppas n < 0.44), with 72.4% and 68.7% cumulative release at 48 h from SLNM and SLNCP, respectively, compared to rapid release of free DBC. MTT assays on BALB/c 3T3 fibroblasts and HaCaT keratinocytes indicated significantly reduced cytotoxicity (>85% viability at 2.1 mmol/L vs. <60% for free DBC). In vivo tail-flick tests in Wistar rats demonstrated prolonged antinociception, with recovery time extended by 142% (SLNM) and 128% (SLNCP) compared to free DBC (p < 0.01). These results establish DBC-loaded SLNs as a promising, biocompatible nanoplatform for safer, longer-acting local anesthesia, with potential applications in infiltrative and postoperative pain management.

Keywords: Dibucaine, Solid Lipid Nanoparticles, High-Pressure Homogenization, Sustained Release, Local Anaesthesia.