A bubble bursting-mediated oral drug delivery system that enables concurrent delivery of lipophilic and hydrophilic chemotherapeutics for treating pancreatic tumors in rats
Journal
Biomaterials
Journal Volume
255
Pages
120157
Date Issued
2020
Author(s)
Kuan-Hung Chen ; Yang-Bao Miao ; Chun-Yu Shang ; Tring-Yo Huang ; Yu-Tzu Yu ; Chun-Nan Yeh ; Chiung-Tong Chen ; Fwu-Long Mi ; Kun-Ju Lin ; Hsing-WenSung
Abstract
The therapeutic outcome of pancreatic cancer remains unsatisfactory, despite many attempts to improve it. To address this challenge, an oral drug delivery system that spontaneously initiates an effervescent reaction to form gas-bubble carriers is proposed. These carriers concurrently deliver lipophilic paclitaxel (PTX) and hydrophilic gemcitabine (GEM) in the small intestine. The bursting of the bubbles promotes the intestinal absorption of the drugs. The antitumor efficacy of this proposed oral drug delivery system is evaluated in rats with experimentally created orthotopic pancreatic tumors. The combined administration of equivalent amounts of PTX and GEM via the intravenous (i.v.) route, which is clinically used for treating pancreatic cancer, serves as a control. Following oral administration, the lipophilic PTX is initially absorbed through the intestinal lymphatic system and then enters systemic circulation, whereas the hydrophilic GEM is directly taken up into the blood circulation, ultimately accumulating in the tumorous pancreatic tissues. A pharmacokinetic study reveals that the orally delivered formulation has none of the toxic side-effects that are associated with the i.v. injected formulation; changes the pharmacokinetic profiles of the drugs; and increases the bioavailability of PTX. The oral formulation has a greater impact than the i.v. formulation on tumor-specific stromal depletion, resulting in greater inhibition of tumor growth with no evidence of metastatic spread. As well as enhancing the therapeutic efficacy, this unique approach of oral chemotherapy has potential for use on outpatients, greatly improving their quality of life. ? 2020 Elsevier Ltd
Subjects
Bubble bursting; Effervescent reaction; Gemcitabine; Paclitaxel; Pancreatic adenocarcinoma
SDGs
Other Subjects
Biochemistry; Cardiovascular system; Chemotherapy; Diseases; Drug interactions; Hydrophilicity; Pharmacokinetics; Rats; Targeted drug delivery; Tumors; Inhibition of tumor growth; Intestinal absorption; Oral drug delivery system; Pharmacokinetic profiles; Pharmacokinetic studies; Systemic circulation; Therapeutic efficacy; Therapeutic outcomes; Controlled drug delivery; gemcitabine; paclitaxel; drug carrier; paclitaxel; animal cell; animal experiment; animal model; antineoplastic activity; Article; cancer growth; circulation; controlled study; drug absorption; drug accumulation; drug bioavailability; drug blood level; drug delivery system; drug distribution; drug efficacy; drug elimination; drug formulation; drug half life; hydrophilicity; intestine absorption; lipophilicity; male; nonhuman; pancreas cancer; priority journal; rat; animal; chemical phenomena; drug delivery system; oral drug administration; pancreas tumor; quality of life; tumor cell line; Administration, Oral; Animals; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Hydrophobic and Hydrophilic Interactions; Paclitaxel; Pancreatic Neoplasms; Quality of Life; Rats
Type
journal article