Pallvi Bragta1, Rupinder Kaur Sidhu1, Kiran Jyoti2, Ashish Baldi3, Upendra Kumar Jain1, Ramesh Chandra4, Jitender Madan5. 1. Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India. 2. Department of Pharmaceutics, Sachdeva College of Pharmacy, Mohali, Punjab, India. 3. Department of Pharmaceutical Science and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India. 4. Dr B.R Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, India; Department of Chemistry, University of Delhi, Delhi, India. 5. Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India. Electronic address: jitenderpharmacy@gmail.com.
Abstract
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 IC50 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-mm3 as compared to 178.9 ± 10.2-mm3 of CBDCA solution injected i.t. and 210.6 ± 17.1-mm3 displayed by CBDCA solution injected i.v. vis-à-vis 815.4 ± 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.
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 IC50 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-mm3 as compared to 178.9 ± 10.2-mm3 of CBDCA solution injected i.t. and 210.6 ± 17.1-mm3 displayed by CBDCA solution injected i.v. vis-à-vis 815.4 ± 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.