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.

尽管进行了许多尝试，胰腺癌的治疗结果仍然不能令人满意。为了解决这一挑战，提出了一种口服药物递送系统，其自发地起泡反应以形成气泡载体。这些载体同时在小肠中递送亲脂性紫杉醇（PTX）和亲水性吉西他滨（GEM）。气泡的破裂促进了药物的肠道吸收。在具有实验产生的原位胰腺肿瘤的大鼠中评估了该提议的口服药物递送系统的抗肿瘤功效。当量PTX和GEM的联合施用通过临床上用于治疗胰腺癌的静脉内（iv）途径可作为对照。口服后，亲脂性PTX首先通过肠淋巴系统吸收，然后进入体循环，而亲水性GEM直接进入血液循环，最终在肿瘤性胰腺组织中蓄积。药代动力学研究表明，口服给药的制剂没有与静脉注射制剂有关的毒性副作用。改变药物的药代动力学特征；并增加了PTX的生物利用度。口服制剂比静脉制剂对肿瘤特异性基质耗竭具有更大的影响，导致对肿瘤生长的更大抑制，没有转移扩散的迹象。