Prevention of lung cancer recurrence using cisplatin-loaded superhydrophobic nanofiber meshes

Abstract

For early stage lung cancer patients, local cancer recurrence after surgical resection is a significant concern and stems from microscopic disease left behind after surgery. Here we apply a local drug delivery strategy to combat local lung cancer recurrence after resection using non-woven, biodegradable nanofiber meshes loaded with cisplatin. The meshes are fabricated using a scalable electrospinning process from two biocompatible polymers—polycaprolactone and poly(glycerol monostearate-co-caprolactone)—to afford favorable mechanical properties for use in a dynamic tissue such as the lung. Owing to their rough nanostructure and hydrophobic polymer composition, these meshes exhibit superhydrophobicity, and it is this non-wetting nature that sustains the release of cisplatin in a linear fashion over ~90 days, with anti-cancer efficacy demonstrated using an in vitro Lewis Lung carcinoma (LLC) cell assay. The in vivo evaluation of cisplatin-loaded superhydrophobic meshes in the prevention of local cancer recurrence in a murine model of LLC surgical resection demonstrated a statistically significant increase (p = 0.0006) in median recurrence-free survival to >23 days, compared to standard intraperitoneal cisplatin therapy of equivalent dose. These results emphasize the importance of supplementing cytoreductive surgery with local drug delivery strategies to improve prognosis for lung cancer patients undergoing tumor resection.

microRNA-605 promotes cell proliferation, migration and invasion in non-small cell lung cancer by directly targeting LATS2

“…Recently, the therapeutic treatments have made great progress; however, the prognosis for patients with NSCLC remains poor and the five-year overall survival rate is only 15% (6). An increasing number of evidences indicated that tumor metastasis and recurrence are frequent, and huge challenges in the therapy of NSCLC, and mostly responsible for the low five-year survival rate (7)(8)(9)(10). Cumulatively, this highlights the urgent need to fully understand the mechanism on NSCLC formation and progression and identify novel therapeutic strategies.…”

Superhydrophobic materials for biomedical applications

“…in the Grinstaff laboratory [221] investigated the release of cisplatin from electrospun superhydrophobic meshes, again using PCL and PGC-C18 polymer blends. Drug release and extended cytotoxicity against Lewis Lung Carcinoma (LLC) cells is observed over 90 days, which corresponded to the infiltration time for a solution of 10% fetal bovine serum (FBS), as imaged by CT. To our knowledge, this is the longest reported underwater layer maintenance in the presence of significant protein.…”

Early stage release control of an anticancer drug by drug-polymer miscibility in a hydrophobic fiber-based drug delivery system

“…24,27,28 While an earlier study 29 partly demonstrated the effect of drug-polymer-solvent compatibility on drug release proles, further analytical work is necessary to explain the phenomena. Of major interest of this study is to: (1) investigate the inuence of drug-polymer miscibility on the drug release proles from hydrophobic ber mats; (2) analyze the drug localization in the polymeric matrix; and (3) examine the effectiveness of drug delivery by in vitro cytotoxicity assay. Drug-loaded ber mats were prepared by electrospinning of solution precursors containing poly(lactic acid) (PLA) and either hydrophilic Dox (DoxHCl) or hydrophobic Dox (Dox-base).…”

“…[2][3][4][5][6] Of the ber-forming processes, electrospinning has been widely adopted as a versatile method to produce brous vehicles with ne-tuned morphology for effective delivery of therapeutic agents. [1][2][3]5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20] For example, multi-axial electrospinning has been utilized to produce multi-compartmental bers that allow multiple release stages or multi-drug delivery. 5,10,18 This conguration has a potential application of treating patients who have developed resistance to specic drugs.…”