Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma

Abstract

Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Here, the controlled release of OP from a biodegradable PLGA cylinder (PLGA-OP) implanted at tumor site was investigated for its role in limiting tumor neovascularization, growth, and metastasis. PLGA-OP cylinders over 30 days in vitro indicated 20%–25% release profiles within 48 hours followed by a continuous metronomic low dose release of 30%–50% OP for an additional 16 days. All OP was released by day 30. Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort. Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31+ endothelial cells compared with the untreated cohort. These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer.

Innovative nanotheranostics: Smart nanoparticles based approach to overcome breast cancer stem cells mediated chemo‐ and radioresistances

“…They also improve the drugs' extended‐release profile (DeCarlo et al, 2021). Traditionally, polyethylene glycol (PEG) is mainly used for extended‐release based surface modification purposes (Xu et al, 2021) but recently poly(lactic‐ co ‐glycolic acid) (PLGA) polymers (Hrynyk et al, 2015) or injectable pickering emulsions (IPEs) (Wood et al, 2018) approaches have been used extensively.…”

Recent developments in Pickering emulsions for biomedical applications

“…A challenge associated with intravenous formulations is designing their controlled, sustained release, which can significantly lower systemic exposure to non-target organs, and aids in significant release of the therapeutic at the target site. Neufeld and co-workers have been working on such slow-release systems for a number of years, [31,32] most recently preparing W/O Pickering emulsions stabilised by glycerol monostearate for the delivery of an anti-cancer therapeutic oseltamivir phosphate which targets mammalian neuraminidase 1 involved in multistage tumorigenesis in a number of cancer types.…”