Abstract
Conventional oral isoniazid (INH) causes severe side effects, toxicity and poor patient compliance. INH loaded elastic liposomes (ELs) were fabricated with phosphatidylcholine (PC) and edge activators (EA) possessing innate anti-tubercular activity. A full factorial design was applied to two factors (PC as X-1 and EA as X-2) and four dependent variables (size as Y-1, zeta potential as Y-2, % entrapment as Y-3 and flux as Y-4). The optimized formulation (OEL) was characterized for comparison. To confirm mechanistic views of permeation/deposition and penetration across the rat skin, a differential scanning calorimeter (DSC), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used. The F18 had the least vesicle size (similar to 78.6 nm) and optimum zeta potential (-25.31 mV) as per formulations comprised of the sodium deoxycholate and span 80. The OEL (X-1 similar to 82.5 mg and X-2 similar to 30.5 mg) exhibited a good correlation between the predicted and the observed values with maximum desirability (0.943) and no observed interaction (factors). Morphological and extrusion studies ensured the spherical and deformable vesicle of the OEL. All the ELs were hemocompatible and showed sustained drug release as per diffusion studies (n < 0.5). The permeation flux of the OEL was 1.8-, 1.4-, 1.8-, 1.6- and 8.2 fold higher than those for F3, F7, F11, F15, and the drug solution, respectively. The DSC and SEM showed reversible perturbation whereas the CLSM corroborated penetration into the skin. Thus, the ELs could be an effective approach controlling cutaneous and systemic tuberculosis.