Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India.
Department of Pharmaceutics, Sachdeva College of Pharmacy, Mohali, Punjab, India.
Colloids Surf B Biointerfaces. 2018 Jun 1;166:339-348. doi: 10.1016/j.colsurfb.2018.03.009. Epub 2018 Mar 31.
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.
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.
The promising preclinical results of CBDCA-PCL-NPs-Gel warrant further investigations under a set of stringent parameters for the treatment of melanoma.
在一项 II 期临床试验中，卡铂（CBDCA）在治疗恶性黑色素瘤方面的反应率与达卡巴嗪相当，为 19%。然而，除了理想的治疗特征外，静脉（i.v）给予 CBDCA 会在靶部位提供亚治疗浓度。这需要通过使用纳米载体通过替代途径给予 CBDCA，以实现治疗黑色素瘤的疗效。
制备载有卡铂的聚（ε-己内酯）纳米粒（CBDCA-PCL-NPs）并与壳聚糖-β-甘油磷酸凝胶（CBDCA-PCL-NPs-Gel）混合，用于瘤内（i.t）给药。 CBDCA-PCL-NPs 的平均粒径和 Zeta 电位分别为 54.5±6.3nm 和-8.1±0.9mV，此外纳米制剂还呈球形。傅里叶变换红外光谱（FT-IR）表明药物与聚合物之间没有任何化学不相容性问题。 XRD 图谱表明 CBDCA-PCL-NPs 具有无定形晶格。 CBDCA-PCL-NPs-Gel 的药物载量估计为 152mg/1ml。 CBDCA-PCL-NPs-Gel 表现出长达 48 小时的药物释放延长。此外，CBDCA-PCL-NPs-Gel 的 IC50 为 80.3-μM，明显（P<0.05）低于 CBDCA-PCL-NPs 的 162.8-μM 和 CBDCA 溶液的 248.5-μM，在 B16F1 黑色素瘤癌细胞中。 CBDCA-PCL-NPs-Gel 验证了 80.2%的凋亡率明显（P<0.01）高于 CBDCA-PCL-NPs 的 57.6%和 CBDCA 溶液的 43.4%。在此基础上，与瘤内注射 CBDCA 溶液相比，CBDCA-PCL-NPs-Gel 显著（P<0.01）抑制肿瘤体积至 95.5±8.4-mm3，而瘤内注射 CBDCA 溶液时为 178.9±10.2-mm3，静脉注射 CBDCA 溶液时为 210.6±17.1-mm3，而 B16F1 荷瘤 C57BL6J 小鼠的肿瘤体积为 815.4±17.1-mm3。
CBDCA-PCL-NPs-Gel 的有希望的临床前结果需要在一系列严格的参数下进行进一步研究，以用于治疗黑色素瘤。
