POTENTIAL OF TRANSFERSOMAL DELIVERY SYSTEM IN IMPROVING THE THERAPEUTIC OUTCOME OF LAPATANIB IN BREAST CANCER TREATMENT

Objective: This study aimed to develop and optimize lapatinib ditosylate(LAP)- loaded transferosomes using a 32-factorial design. Methods: LAP-loaded transferosomes were prepared by the rotary thin-film hydration method using Labrafac Lipophile WL1349 and Tween 80. The independent variables in transferosome preparation were the amount of Labrafac Lipophile WL1349 (X1) and Tween 80 (X2). The dependent variables analyzed were vesicle size (Y1) and percent entrapment efficiency (%EE) (Y2). The resulting transferosomes were characterized for several parameters: drug content, particle size distribution, entrapment efficiency, zeta potential(ZP), polydispersity index(PDI), and morphology via transmission electron microscopy (TEM). In vitro drug release studies were also performed. The optimized transferosomes were then incorporated into a gel formulation, having a good appearanceand a suitable pH, spreadability, and viscosity. The finalized transferosomal gel was further evaluated through in vitro diffusion studies and confocal laser scanning microscopy (CLSM). Results: The optimal LAP-loaded transferosomes displayed a vesicle size of 295 ± 0.13 nm and %EE of 77.4 ± 0.71%, along with a PDI of 0.103 ± 0.024. TEM analysis revealed the vesicles to be spherical with a lamellar structure. The vesicles possessed a high negative surface charge of -44.3 mV, attributed to the presence of Tween 80, indicating strong electrostatic repulsion. In vitro permeation studies showed a sustained release of 84.3 ± 0.38% over 24 hours. The optimized transferosomal formulation was incorporated into a Carbopol 934-based gel. In vitro diffusion studies confirmed that the 2% Carbopol 934 transferosomal gel facilitated enhanced drug release of 87.83± 2.6%. Furthermore, ex vivo permeation studies exhibited a 2.4-fold superior skin penetration compared to less elastic formulations. Conclusion: This research confirms that transferosomes are effective nanoscale carriers for LAP, significantly enhancing skin penetration, as confirmed by a 2.4-fold increase in ex vivo permeation and deep epidermal delivery visualized by CLSM.