Intratumoral administration of carboplatin bearing poly (ε-caprolactone) nanoparticles amalgamated with in situ gel tendered augmented drug delivery, cytotoxicity, and apoptosis in melanoma tumor.

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-β-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 ± 6.3-nm and -8.1 ± 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 152 mg/1 ml. CBDCA-PCL-NPs-Gel demonstrated prolonged drug release up to 48 h. Furthermore, CBDCA-PCL-NPs-Gel displayed the IC of 80.3-μM significantly (P < 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 (P < 0.01) higher than 57.6% of CBDCA-PCL-NPs and 43.4% of CBDCA solution. Continuation to this, CBDCA-PCL-NPs-Gel significantly (P < 0.01) suppressed the tumor volume to 95.5 ± 8.4-mm as compared to 178.9 ± 10.2-mm of CBDCA solution injected i.t. and 210.6 ± 17.1-mm displayed by CBDCA solution injected i.v. vis-à-vis 815.4 ± 17.1-mm 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.