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

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

ABSTRACT

Dibucaine (DBC), a highly potent long-acting local anesthetic, is limited in clinical use due to its narrow therapeutic index, dose-dependent toxicity, and short duration of action in conventional formulations. This study developed DBC-loaded solid lipid nanoparticles (DBC-SLNs) using myristyl myristate (MM) and cetyl palmitate (CP) as lipid matrices via hot emulsion ultrasonication homogenization to achieve enhanced encapsulation, sustained release, reduced cytotoxicity, and prolonged antinociceptive efficacy. Optimized formulations yielded spherical nanoparticles with hydrodynamic diameters of 182.4 ± 4.6 nm (DBC-MM-SLNs) and 214.7 ± 5.2 nm (DBC-CP-SLNs), polydispersity indices <0.25, negative zeta potentials (>-26 mV), and high encapsulation efficiencies of 92.6 ± 1.8% (MM) and 88.4 ± 2.1% (CP). Differential scanning calorimetry confirmed reduced crystallinity (76.8–80.3%), promoting amorphous drug dispersion. In vitro release exhibited biphasic kinetics with initial bursts (28–32%) followed by sustained profiles reaching 78.6% (MM) and 72.3% (CP) over 48 h, best fitted by the Korsmeyer-Peppas model (n ≈ 0.5, anomalous transport). Encapsulation significantly attenuated toxicity, elevating IC₅₀ values ~2-fold in BALB/c 3T3 fibroblasts and HaCaT keratinocytes, and reducing hemolysis to <5% at 2 mg/mL DBC equivalent. In vivo tail flick tests in Wistar rats demonstrated 2.0–2.3-fold increases in area under the % maximum possible effect curve, with sustained >50% antinociception up to 240 min for MM-SLNs versus 60 min for free DBC, without local irritation. These results indicate that DBC-SLNs, particularly MM-based, offer a promising nanocarrier platform for safer, longer-acting topical anaesthesia, potentially expanding DBC's therapeutic applications while minimising systemic risks.

Keywords: Dibucaine; Solid lipid nanoparticles; Sustained release; Local anesthetic; Nanotoxicity reduction.