Nanodrug Delivery Systems for the Treatment of Ovarian Cancer.

Despite advances achieved in medicine, chemotherapeutics still has detrimental side effects with ovarian cancer (OC), accounting for numerous deaths among females. The provision of safe, early detection and active treatment of OC remains a challenge, in spite of improvements in new antineoplastic discovery. Nanosystems have shown remarkable progress with impact in diagnosis and chemotherapy of various cancers, due to their ideal size; improved drug encapsulation within its interior core; potential to minimize drug degradation; improve in vivo drug release kinetics; and prolong blood circulation times. However, nanodrug delivery systems have few limitations regarding its accuracy of tumour targeting and the ability to provide sustained drug release. Hence, a cogent and strategic approach has focused on nanosystem functionalization with antibody-based ligands to selectively enhance cellular uptake of antineoplastics. Antibody functionalized nanosystems are (advanced) synthetic candidates, with a broad range of efficiency in specific tumour targeting, whilst leaving normal cells unaffected. This article comprehensively reviews the present status of nanosystems, with particular emphasis on nanomicelles for molecular diagnosis and treatment of OC. In addition, biomarkers of nanosystems provide important prospects as chemotherapeutic strategies to upsurge the survival rate of patients with OC.

Chemotherapeutic Efficacy of Implantable Antineoplastic-Treatment Protocols in an Optimal Mouse Model for Human Ovarian Carcinoma Cell Targeting.

The present study aimed to design and develop a nanocomposite drug delivery system employing an antineoplastic-loaded antibody functionalized nanomicelle encapsulated within a Chitosan⁻Poly(vinylpyrrolidone)⁻Poly(N-isopropylacrylamide) (C⁻P⁻N) hydrogel to form an in situ forming implant (ISFI), responsive to temperature and pH for cancer cell-targeting following intraperitoneal implantation. The optimum nanomicelle formulation was surface-functionalized with anti-MUC 16 (antibody) for the targeted delivery of methotrexate to human ovarian carcinoma (NIH:OVCAR-5) cells in Athymic nude mice that expressed MUC16, as a preferential form of intraperitoneal ovarian cancer (OC) chemotherapy. The cross-linked interpenetrating C⁻P⁻N hydrogel was synthesized for the preparation of an in situ-forming implant (ISFI). Subsequently, the ISFI was fabricated by encapsulating a nanocomposite comprising of anti-MUC16 (antibody) functionalized methotrexate (MTX)-loaded poly(N-isopropylacrylamide)-b-poly(aspartic acid) (PNIPAAm-b-PASP) nanomicelles (AF(MTX)NM's) within the cross-linked C⁻P⁻N hydrogel. This strategy enabled specificity and increased the residence time of the nanomicelles at tumor sites over a period exceeding one month, enhancing uptake of drugs and preventing recurrence and chemo-resistance. Chemotherapeutic efficacy was tested on the optimal ovarian tumor-bearing Athymic nude mouse model and the results demonstrated tumor regression including reduction in mouse weight and tumor size, as well as a significant (p < 0.05) reduction in mucin 16 levels in plasma and ascitic fluid, and improved survival of mice after treatment with the experimental anti-MUC16/CA125 antibody-bound nanotherapeutic implant drug delivery system (ISFI) (p < 0.05). The study also concluded that ISFI could potentially be considered an important immuno-chemotherapeutic agent that could be employed in human clinical trials of advanced, and/or recurring, metastatic epithelial ovarian cancer (EOC). The development of this ISFI may circumvent the treatment flaws experienced with conventional systemic therapies, effectively manage recurrent disease and ultimately prolong disease-free intervals in ovarian cancer patients.