Abstract
Research on metastasis is gaining momentum for effective cancer management. Berbamine (BBM) has the potency to act as a therapeutic in multiple cancers and cancer metastasis. However, the major limitation of the compound includes poor bioavailability at the tumor site due to short plasma half-life. Here, our major objective involved development of lipid based nanoparticles (NPs) loaded with BBM with an aim to circumvent the above problem. Moreover its, therapeutic potentiality was evaluated through various in vitro cellular studies and in vivo melanoma primary and experimental lung metastatic tumor model in C57BL/6 mice. Results of different cellular experiments demonstrated enhanced therapeutic efficacy of BBM-NPs in inhibiting metastasis, cell proliferation and growth as compared to native BBM in highly metastatic cancer cell lines. Further, in vivo results demonstrated suppression of primary B16F10 melanoma tumor growth in C57BL/6 mice model treated with BBM-NPs than that of native BBM. Importantly, a moderately cytotoxic dose of BBM-NPs was able to significantly suppress the incidence of B16F10 cells lung metastasis in vivo. Results indicated development of an effective approach for aggressive metastatic cancer.
Highlights
Despite new advancement of different therapeutics for treatment of cancer, till date metastasis is regarded as one of the most formidable bottleneck for effective cancer management
The therapeutic evaluation of BBM-NPs on primary tumor was evaluated by melanoma (B16F10) subcutaneous tumor model and effect on metastasis was evaluated through hematogenous metastasis of melanoma cells to lung
Results revealed that the crystalline peaks obtained in case of native BBM are not present in case of BBM-NPs suggesting that BBM is in amorphous or disordered crystalline phase in the polymer matrix of NPs (Fig. 1c)
Summary
Despite new advancement of different therapeutics for treatment of cancer, till date metastasis is regarded as one of the most formidable bottleneck for effective cancer management. Have been well documented for the treatment of metastatic cancer in recent years due to their wide range of biological activities with reduced toxicity over chemotherapeutic regimes[12,13,14] In this regard, Berbamine (BBM), a bisbenzylisoquinoline alkaloid extracted from a plant Berbaris amurensis has shown its potency against multitude of diseases including cancer[15]. Delivering therapeutic dose of BBM in sustained fashion at tumor site is a prerequisite for clinical implementation of this potent anticancer drug In this context, nanotechnology has paved the way for new discoveries of drug delivery vehicles by improving the clinical therapeutic efficacy of the drugs by increasing the amount of drug deposited in the tumor tissues while decreasing its accumulation in healthy tissues, for better cancer treatment[19]. The above study signifies that, BBM-NPs can be a better candidate for the treatment of metastatic cancer
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