Paclitaxel loaded biodegradable polymeric fabric for intraperitoneal drug delivery in ovarian cancer

Abstract

Intraperitoneal(IP)chemotherapy for metastatic ovarian cancer works on the pharmacokinetic rationale of sustained exposure of tumor cells in the peritoneum to high drug concentrations. Despite the significant patient survival benefits demonstrated in several clinical trials and the resultant NCI approval, the clinical adoption of IP therapy has not been very successful.The primary reasons have been pointed out as the complications caused by the indwelling IP catheters used for delivering drugs,need for frequent intermittent dosing and the intolerable toxicity issues imposed by the bolus drug doses. In this context, an ideal IP drug delivery system which can tackle these issues and most importantly, address the challenge of achieving a continuous IP drug elution for prolonged periods without toxicity concerns, would be a potential solution. Additionally, the clinical requirement is to develop an easily implantable drug depot which can be fixed or sutured to the peritoneal cavity wall such that it does not obstruct the normal functioning of peritoneum. These design attributes, if successfully accomplished can favour the implementation of an IP drug delivery strategy which is compliant to patients as well as practically feasible for the clinicians.In this work, paclitaxel (PTX) loaded polydioxanone (PDS) nanoyarns developed by electrospinning, have been woven into nanotextile fabric implants and optimized for the purpose of long term continuous IP drug delivery for ovarian cancer therapy. An attempt for mechanistic modelling of the in vitro drug release from the nanoyarns has proved the role of unique architecture of nanoyarns in attaining a slow and sustained drug release for ~3 months by a combination of drug diffusion and polymer degradation. The modulation of yarn packing density of the fabric implants served as a critical parameter for achieving tuneable drug release rates. Further, in vivo studies in healthy mice with the loosely packed woven fabric implant sutured to peritoneal wall conferred a sustained...