Drug-eluting scaffold to deliver chemotherapeutic medication for management of pancreatic cancer after surgery

Abstract

Traditional post-surgical chemotherapy for pancreatic cancer is notorious for its devastating side effects due to the high dosage required. On the other hand, legitimate concerns have been raised about nanoparticle-mediated drug delivery because of its potential cytotoxicity. Therefore, we explored the local delivery of a reduced dosage of FOLFIRINOX, a four-drug regimen comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil, for pancreatic cancer using a biocompatible drug-eluting scaffold as a novel chemotherapy strategy after palliative surgery. In vitro assays showed that FOLFIRINOX in the scaffold caused massive apoptosis and thereby a decrease in the viability of pancreatic cancer cells, confirming the chemotherapeutic capability of the drug-eluting scaffold. In vivo studies in an orthotopic murine xenograft model demonstrated that the FOLFIRINOX in the scaffold had antitumorigenic and antimetastatic effects comparable with those achieved by intraperitoneal injection, despite the dose released by the scaffold being roughly two thirds lower. A mechanistic study attributed our results to the excellent ability of the FOLFIRINOX in the scaffold to destroy the CD133 + CXCR4+ cell population responsible for pancreatic tumorigenesis and metastasis. This clinically oriented study gives rise to a promising alternative strategy for postsurgical management of pancreatic cancer, featuring a local chemotherapeutic effect with considerable attenuation of side effects.

Synergistic effect of a drug loaded electrospun patch and systemic chemotherapy in pancreatic cancer xenograft

“…For the non-eluting patch (sham patch), the blended solution without 5-FU was electrospun under the same conditions. After electrospinning, the scaffolds were desiccated in a vacuum for 72 h. The fully dried patches were weighed uniformly at 20 mg, cut into squares, and stored at −20 °C 53 . A scanning electron microscope (SEM; Hitachi SU-6600, Hitachi, Tokyo, Japan) was used to analyse the morphology of the electrospun patches.…”

“…A scanning electron microscope (SEM; Hitachi SU-6600, Hitachi, Tokyo, Japan) was used to analyse the morphology of the electrospun patches. The samples were platinum-coated by a sputter-coater and imaged using an accelerating voltage of 15 kV 53 .…”

TARTESSUS: A Customized Electrospun Drug Delivery System Loaded with Irinotecan for Local and Sustained Chemotherapy Release in Pancreatic Cancer

“…Moreover, regarding the pattern release of the A and B type membranes, no similar results were found in the available literature for in vitro studies. However, some authors did find a similar distribution release to the A type on in vivo studies [6,9,[13][14][15]. On the other hand, C-type membranes showed an early release of irinotecan.…”

“…As an alternative to systemic adjuvant therapy, local drug delivery systems (DDSs) [5,[9][10][11] have been designed to be implanted directly into the tumor bed after surgery and provide sustained drug release to the tumor site, which can overcome drug transport barriers and reduce side effects as well as improve patient adherence [12] DDSs are responsible for drug delivery in a specific way, either by attacking tumor cells directly and exclusively or by leading conventional drugs to the affected organ [11]. Some examples of DDSs are patches [13,14], hydrogels [15,16], nanoparticles, even using new carriers such as MCM-41, MCM-48, or SBA-15 [17][18][19][20][21], or electrospun meshes [8,9,[22][23][24]. Compared to traditional systemic or regional chemotherapy, local administration of the drug using a drug-eluting scaffold reduces the dose required to achieve a comparable anti-cancer effect by approximately two-thirds [8].…”

“…On the other hand, the DDSs studied thus far [5,[9][10][11] have produced an immediate release of the chemotherapeutic, which can be risky in the case of using it after resection surgery for pancreatic cancer. The risk is not only due to the possible systemic effects it may have in the recently intervened patient, but also because of the local effects in the area where the device is located such as infection, bleeding, or wound dehiscence.…”