Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment

At present, the 10-year survival rate of patients with pancreatic cancer is still less than 4%, mainly due to the high cancer recurrence rate caused by incomplete surgery and lack of effective postoperative adjuvant treatment. Systemic chemotherapy remains the only choice for patients after surgery;...

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Main Authors: Xiangming Kong, Miao Feng, Lihuang Wu, Yiyan He, Hongli Mao, Zhongwei Gu
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Drug Delivery
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/10717544.2022.2075984
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author Xiangming Kong
Miao Feng
Lihuang Wu
Yiyan He
Hongli Mao
Zhongwei Gu
author_facet Xiangming Kong
Miao Feng
Lihuang Wu
Yiyan He
Hongli Mao
Zhongwei Gu
author_sort Xiangming Kong
collection DOAJ
description At present, the 10-year survival rate of patients with pancreatic cancer is still less than 4%, mainly due to the high cancer recurrence rate caused by incomplete surgery and lack of effective postoperative adjuvant treatment. Systemic chemotherapy remains the only choice for patients after surgery; however, it is accompanied by off-target effects and server systemic toxicity. Herein, we proposed a biodegradable microdevice for local sustained drug delivery and postoperative pancreatic cancer treatment as an alternative and safe option. Biodegradable poly(l-lactic-co-glycolic acid) (P(L)LGA) was developed as the matrix material, gemcitabine hydrochloride (GEM·HCl) was chosen as the therapeutic drug and polyethylene glycol (PEG) was employed as the drug release-controlled regulator. Through adjusting the amount and molecular weight of PEG, the controllable degradation of matrix and the sustained release of GEM·HCl were obtained, thus overcoming the unstable drug release properties of traditional microdevices. The drug release mechanism of microdevice and the regulating action of PEG were studied in detail. More importantly, in the treatment of the postoperative recurrence model of subcutaneous pancreatic tumor in mice, the microdevice showed effective inhibition of postoperative in situ recurrences of pancreatic tumors with excellent biosafety and minimum systemic toxicity. The microdevice developed in this study provides an option for postoperative adjuvant pancreatic treatment, and greatly broadens the application prospects of traditional chemotherapy drugs.
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spelling doaj.art-b178a52037c949739874c6b05077c3b62022-12-22T02:29:06ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-012911595160710.1080/10717544.2022.2075984Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatmentXiangming Kong0Miao Feng1Lihuang Wu2Yiyan He3Hongli Mao4Zhongwei Gu5College of Materials Science and Engineering, Research Institute for Biomaterials, Tech Institute for Advanced Materials, Nanjing Tech University, Nanjing, PR ChinaCollege of Materials Science and Engineering, Research Institute for Biomaterials, Tech Institute for Advanced Materials, Nanjing Tech University, Nanjing, PR ChinaCollege of Materials Science and Engineering, Research Institute for Biomaterials, Tech Institute for Advanced Materials, Nanjing Tech University, Nanjing, PR ChinaCollege of Materials Science and Engineering, Research Institute for Biomaterials, Tech Institute for Advanced Materials, Nanjing Tech University, Nanjing, PR ChinaCollege of Materials Science and Engineering, Research Institute for Biomaterials, Tech Institute for Advanced Materials, Nanjing Tech University, Nanjing, PR ChinaCollege of Materials Science and Engineering, Research Institute for Biomaterials, Tech Institute for Advanced Materials, Nanjing Tech University, Nanjing, PR ChinaAt present, the 10-year survival rate of patients with pancreatic cancer is still less than 4%, mainly due to the high cancer recurrence rate caused by incomplete surgery and lack of effective postoperative adjuvant treatment. Systemic chemotherapy remains the only choice for patients after surgery; however, it is accompanied by off-target effects and server systemic toxicity. Herein, we proposed a biodegradable microdevice for local sustained drug delivery and postoperative pancreatic cancer treatment as an alternative and safe option. Biodegradable poly(l-lactic-co-glycolic acid) (P(L)LGA) was developed as the matrix material, gemcitabine hydrochloride (GEM·HCl) was chosen as the therapeutic drug and polyethylene glycol (PEG) was employed as the drug release-controlled regulator. Through adjusting the amount and molecular weight of PEG, the controllable degradation of matrix and the sustained release of GEM·HCl were obtained, thus overcoming the unstable drug release properties of traditional microdevices. The drug release mechanism of microdevice and the regulating action of PEG were studied in detail. More importantly, in the treatment of the postoperative recurrence model of subcutaneous pancreatic tumor in mice, the microdevice showed effective inhibition of postoperative in situ recurrences of pancreatic tumors with excellent biosafety and minimum systemic toxicity. The microdevice developed in this study provides an option for postoperative adjuvant pancreatic treatment, and greatly broadens the application prospects of traditional chemotherapy drugs.https://www.tandfonline.com/doi/10.1080/10717544.2022.2075984Biodegradable microdevicesustained releaseimplantationlocal treatmenttumor recurrence inhibition
spellingShingle Xiangming Kong
Miao Feng
Lihuang Wu
Yiyan He
Hongli Mao
Zhongwei Gu
Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment
Drug Delivery
Biodegradable microdevice
sustained release
implantation
local treatment
tumor recurrence inhibition
title Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment
title_full Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment
title_fullStr Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment
title_full_unstemmed Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment
title_short Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment
title_sort biodegradable gemcitabine loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment
topic Biodegradable microdevice
sustained release
implantation
local treatment
tumor recurrence inhibition
url https://www.tandfonline.com/doi/10.1080/10717544.2022.2075984
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