Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation

نویسندگان

  • Rudra Pangeni
  • Sang Won Choi
  • Ok-Cheol Jeon
  • Youngro Byun
  • Jin Woo Park
چکیده

Oxaliplatin (OXA) is a third-generation cisplatin analog that has been approved as first-line chemotherapy in combination with 5-fluorouracil (5-FU) for the treatment of resectable and advanced colorectal cancer. However, the therapeutic efficacy of oral OXA and 5-FU is limited by their low bioavailability due to poor membrane permeability. The aim of the present study was to develop an oral delivery system for OXA and 5-FU. We constructed an ion-pairing complex of OXA with a deoxycholic acid derivative (Nα-deoxycholyl-l-lysyl-methylester, DCK) (OXA/DCK) as a permeation enhancer. Next, we prepared multiple water-in-oil-in-water nanoemulsions incorporating OXA/DCK and 5-FU to enhance their oral absorption. To evaluate their membrane permeability, we assessed in vitro permeabilities of OXA/DCK and 5-FU through an artificial intestinal membrane and Caco-2 cell monolayer. Finally, oral bioavailability in rats and tumor growth inhibition in the colorectal adenocarcinoma cell (CT26)-bearing mouse model were investigated after oral administration of nanoemulsion containing OXA/DCK and 5-FU. The droplet size of the optimized nanoemulsion was 20.3±0.22 nm with a zeta potential of -4.65±1.68 mV. In vitro permeabilities of OXA/DCK and 5-FU from the nanoemulsion through a Caco-2 cell monolayer were 4.80- and 4.30-fold greater than those of OXA and 5-FU, respectively. The oral absorption of OXA/DCK and 5-FU from the nanoemulsion also increased significantly, and the resulting oral bioavailability values of OXA/DCK and 5-FU in the nanoemulsive system were 9.19- and 1.39-fold higher than those of free OXA and 5-FU, respectively. Furthermore, tumor growth in CT26 tumor-bearing mice given the oral OXA/DCK- and 5-FU-loaded nanoemulsion was maximally inhibited by 73.9%, 48.5%, and 38.1%, compared with tumor volumes in the control group and the oral OXA and 5-FU groups, respectively. These findings demonstrate the therapeutic potential of a nanoemulsion incorporating OXA/DCK and 5-FU as an oral combination therapy for colorectal cancer.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Preparation and In Vitro Evaluation of a Microballoon Delivery System for Theophylline

A multiple-unit oral floating system was prepared using the emulsification-solvent diffusion method to prolong the gastric emptying time of theophylline. For this purpose, theophylline, ethyl cellulose and dibutyl phthalate were dissolved in an ethanol/dichloromethane mixture, added to 0.1 M HCl containing NaCl (20%) or saturated theophylline and/or different concentrations of polysorbate 80 an...

متن کامل

Preparation and In Vitro Evaluation of a Microballoon Delivery System for Theophylline

A multiple-unit oral floating system was prepared using the emulsification-solvent diffusion method to prolong the gastric emptying time of theophylline. For this purpose, theophylline, ethyl cellulose and dibutyl phthalate were dissolved in an ethanol/dichloromethane mixture, added to 0.1 M HCl containing NaCl (20%) or saturated theophylline and/or different concentrations of polysorbate 80 an...

متن کامل

In vivo evaluation of physiological efficacy of insulin-loaded nanoliposomes prepared for oral delivery

Introduction: Oral delivery is the most favorable route for insulin administration. The aim of this study was to generate new chitosan coated insulin nanoliposomes and then to assess the physiological efficacy of these nanoliposomes after oral administration in diabetic rabbits. Methods: Nanoliposomes with negative surface charge encapsulating insulin were prepared by reverse phase evaporat...

متن کامل

Cationic Immune Stimulating Complexes Containing Soluble Leishmania Antigens: Preparation, Characterization and in Vivo Immune Response Evaluation

Background: Cationic immune stimulating complexes (PLUSCOMs) are particulate antigen delivery systems. PLUSCOMs consist of cationic immunostimulatory complexes (ISCOMs) derivatives and are able to elicit in vivo T cell responses against an antigen. Objective: To evaluate the effects of PLUSCOMs containing Leishmaniamajor antigens (SLA) on the type of immune response generated in the murine mod...

متن کامل

In vivo evaluation of the combination effect of near- infrared laser and PLGA polymer containing 5- fluorouracil – loaded Nano-graphene oxide

Introduction: Recently, nanographene oxide (NGO) is proven to be as a great candidate for drug delivery, and phototherapies cancer. Photothermal sensitivity of NGO and its optical absorption in the NIR region lead to photothermal ablation of tumors. Nevertheless, the major drawback of GO is its toxicity in biological systems, To overcome this problem, nanoscale GO prepare with...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 11  شماره 

صفحات  -

تاریخ انتشار 2016