Localized Controlled Delivery of Gemcitabine via Microsol Electrospun Fibers to Prevent Pancreatic Cancer Recurrence

Abstract

The low radical surgery rate of pancreatic cancer leads to increased local recurrence and poor prognosis. Gemcitabine (GEM) is the preferred chemotherapeutic for pancreatic cancer. However, systemic chemotherapy with GEM has reached a bottleneck due to its serious side effects after frequent injections. In this study, GEM is successfully enwrapped into electrospun fibers via microsol electrospinning technology to form a stable core-shell fibrous structure. The GEM release rate can be adjusted by altering the thickness of the hyaluronan-sol inner fiber and the quantity of loaded GEM, and the release can be sustained for as long as three weeks. In vitro assays show that these electrospun fibers effectively inhibit pancreatic cancer cells and promote apoptosis. In vivo studies show that the fibrous membranes are better for inhibiting the growth of residual tumors than that of integrated tumors. Furthermore, immunohistochemistry results show that GEM-loaded fibers promote a higher cell apoptosis rate than does systemically injected GEM in residual tumors. In addition, the local delivery of GEM with fibers significantly reduces liver toxicity. In summary, a core-shell electrospun fiber for the controlled and localized delivery of GEM, which greatly improves the treatment of residual tumors and prevents pancreatic tumor recurrence, is developed.

Functional Electrospun Fibers for Local Therapy of Cancer

“…In another study, in order to improve post-surgical tumor treatment and prevent tumor recurrence, chemotherapeutic gemcitabine (GEM, used for pancreatic cancer treatment) was dissolved in hyaluronic acid hydrosol then incorporated into PLA nanofibers using micro-sol electrospinning (Fig. 3b) [55]. The core-shell structure it formed contributed to the sustained release of GEM, leading to efficient residual tumor growth inhibition and reduced side effects of GEM.…”

“…To take advantage of this, pH-responsive drug release nanofibers were designed to treat tumor recurrence. Cui et al have worked intensively on pH-responsive electrospun fibers as anti-cancer drug release systems and supporting scaffolds for tissue regeneration via the addition of inorganic components [55,[59][60][61][62]. In one study, sodium bicarbonate was introduced into PLLA fibers together with DOX via emulsion electrospinning to fabricate an acid-responsive scaffold [63], which was shown to have an effect on the inhibition of tumor cells while promoting normal cell proliferation [61].…”

Conditioned medium-electrospun fiber biomaterials for skin regeneration

“…The electrospinning solution of PF was obtained by mixing and stirring 1 g PLA (Jinan Daigang Co. China), 6.42 mL dichloromethane (DCM) and 3 mL N, N-dimethylformamide (DMF) as previous described [ 29 ]. 1 mg HA (Yuancheng Technology Co. Wuhan, China) was respectively dissolved in 1 mL distilled water, 1 mL distilled water containing CM1 lyophilized powder derived from 10 mL CM1, 1 mL distilled water containing CM2 lyophilized powder derived from 10 mL CM2 and 1 mL distilled water containing CM3 lyophilized powder derived from 10 mL CM3 to make 1 wt% HA hydrosol.…”

Electrospun Nanofibers for Drug Delivery and Biosensing

“…Such a system could be implanted upon tumor removal for the prevention of tumor reoccurrence locally. 151 Earlier this year, Hyun Mu et al 157 T cells for up to 9 days, presenting retarded tumor progression with an up to 70% tumor regression. 157 This is an innovative immunotherapeutic approach towards the reinvigoration of the body's non-functional CD8+ cells for suppressing tumor growth.…”