An update on oral drug delivery via intestinal lymphatic transport

Orally administered drug entities have to survive the harsh gastrointestinal environment,penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation.Whereas the gastrointestinal stability can be well maintained by taking proper measures,hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism.The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway.Intestinal lymphatic transport is emerging as a promising pathway to this end.In this review,we intend to provide an updated overview on the rationale,strategies,factors and applications involved in intestinal lymphatic transport.There are mainly two pathways for peroral lymphatic transportdthe chylomicron and the microfold cell pathways.The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

Pharmacokinetics of aminophylline delivered to the small intestine and colon using remote controlled capsules

Background A patented remote controlled capsule （RCC） has recently been developed to provide noninvasive drug delivery to selected sites in the human gut that allows assessment of regional gastrointestinal （GI） drug absorption under a normal physiological environment. The objective of this study was to investigate the rate and extent of aminophylline absorption after site-specific delivery of the drug in the GI tract using RCC and a magnetic marker monitoring （MMM） technique. Methods This study was conducted in twelve healthy male subjects, in a three-treatment, randomized, crossover manner with a 7-day washout. Eligible subjects received a 150 mg aminophylline dose through an oral administration, or via a remote controlled capsule, delivered to the small bowel or ascending colon. MMM was employed to monitor the GI transit of the RCC, and the radio-frequency signal was used to activate capsules at target sites. Blood samples were obtained at regular intervals until 24 hours post dose/activation. Plasma theophylline concentrations were measured by a TDx~ System Analyzer. A comparison of the PK profile with the oral dosing route of aminophylline was performed after delivery to the small bowel and colon. Results The RCC was well tolerated in volunteers. The mean capsule activation time for the small bowel and ascending colon was 2.07 hours and 6.08 hours post dose. Aminophylline had similar absorption profiles from the small bowel compared with the stomach, with an area under the curve （AUCt） ratio of 92% vs. the stomach, but a lower absorption profile from the ascending colon, with an AUCt ratio of 47.2% vs. the stomach. Conclusions The proprietary of the RCC and MMM technique offer the opportunity to obtain data on the intestinal absorption of a drug in humans under noninvasive conditions. Aminophylline is rapidly and efficiently absorbed from the small bowel. While colonic absorption was limited by the poor water condition although effective absorption was observed from the ascending colon. This provides an opportunity for rational development of modified-release formulations as well as alternative dosage forms.

An openable artificial intestinal tract system for the in vitro evaluation of medicines

In vitro drug screening systems for pharmacological targets have been studied as substitutes for whole-animal experiments.Cultured cells or tissues provide promising substitution models when coupled with technological innovations in micro total analysis systems.In this study,we focus on an intestinal drug absorption assay,as the oral route is most frequently used for drug administration.Pharmacological studies have reported the development of artificial vessels that include tubular structures.However,it is difficult to observe the insides of these tubes in situ.To address this problem,we developed a micro-device that uses a pneumatic balloon actuator(PBA)to open and close an artificial intestinal tract.A human colon carcinoma cell line(Caco-2)was cultivated on the flat surface of the micro-device for 7 days to form the inner cellular layer of an artificial intestinal tract with which to evaluate drug transport.The artificial intestinal tract was completely actuated from a flat plate to a circular tube via a PBA with a pressure of 65 kPa,and drugs were perfused at a flow rate of 0.05 mL min^(−1) into the tubular artificial intestinal tract for 1 h.Using the openable artificial intestinal tract,the in vitro absorption of calcein and Texas Red were successfully estimated as models of hydrophilic and hydrophobic drugs,respectively.The artificial intestinal tract enables the effective evaluation of the in vitro intestinal absorption of drug candidates and contributes to the reduction of costs incurred during the initial stage of drug development.