RESUMO
BACKGROUND AND OBJECTIVE: In a phase II clinical trial, carboplatin (CBDCA) displayed the response rate of 19% equivalent to dacarbazine in the treatment of malignant melanoma. However, besides desirable therapeutic profile, intravenous (i.v) administration of CBDCA delivers a subtherapeutic concentration at the target site. This entails administration of CBDCA through an alternate route by using nanovectors to achieve therapeutic efficacy in the treatment of melanoma. METHODS AND RESULTS: Carboplatin loaded poly(ε-caprolactone) nanoparticles (CBDCA-PCL-NPs) were formulated and amalgamated with chitosan-ß-glycerophosphate gel (CBDCA-PCL-NPs-Gel) for intratumoral (i.t) administration. The mean particle size and zeta-potential of CBDCA-PCL-NPs were determined to be 54.5⯱â¯6.3-nm and -8.1⯱â¯0.9-mV, in addition to spherical shape of the nanoformulation. FT-IR spectroscopy denied any issue of chemical incompatibility between drug and polymer. XRD pattern indicated the amorphous lattice of CBDCA-PCL-NPs. The drug loading capacity of CBDCA-PCL-NPs-Gel was estimated to be 152â¯mg/1â¯ml. CBDCA-PCL-NPs-Gel demonstrated prolonged drug release up to 48â¯h. Furthermore, CBDCA-PCL-NPs-Gel displayed the IC50 of 80.3-µM significantly (Pâ¯<â¯0.05) lower than 162.8-µM of CBDCA-PCL-NPs and 248.5-µM of CBDCA solution in B16F1, melanoma cancer cells. CBDCA-PCL-NPs-Gel verified 80.2% of apoptosis significantly (Pâ¯<â¯0.01) higher than 57.6% of CBDCA-PCL-NPs and 43.4% of CBDCA solution. Continuation to this, CBDCA-PCL-NPs-Gel significantly (Pâ¯<â¯0.01) suppressed the tumor volume to 95.5⯱â¯8.4-mm3 as compared to 178.9⯱â¯10.2-mm3 of CBDCA solution injected i.t. and 210.6⯱â¯17.1-mm3 displayed by CBDCA solution injected i.v. vis-à-vis 815.4⯱â¯17.1-mm3 tumor volume of B16F1 tumor bearing C57BL6J mice. CONCLUSION: The promising preclinical results of CBDCA-PCL-NPs-Gel warrant further investigations under a set of stringent parameters for the treatment of melanoma.
