The feasibility of oral targeted drug delivery: Gut immune to particulates?

Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration (oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake.

Effects of lipid-rich food on lymphatic transport of puerarin microemulsion / 中草药

Objective To study the effects of lipid-rick food on lymphatic transport absorption of puerarin microemulsion based on the puerarin microemulsion prepared before. Methods Cycloheximide was used to block lymphatic transport of the microemulsion, and the concentration of puerarin in plasma was determined by HPLC. Bioavailability of blocking group and unblocking group were compared to calculate the proportion of puerarin absorbed by lymphatic transport. Results Administration of lipid did not enhance the proportion of puerarin absorbed by lymphatic transport, compared to administration of water as controls, but microemulsion formulation contribute to the improved lymphatic transport and bioavailability of puerarin. Besides, administration of lipid failed to further increase the lymphatic transport of puerarin microemulsion, but it was evidenced that microemulsion formulation could decrease the effects of lipid-rich food on bioavailability of oral drugs. Conclusion Lipid in food could not enhance the lymphatic transport of puerarin microemulsion and show no significant effects on the bioavailability.

Effects of puerarin-phospholipid complex on lymphatic transport absorption of puerarin microemulsion / 中草药

Objective To study the effects of puerarin-phospholipid complex on lymphatic transport absorption of puerarin microemulsion based on the puerarin-phospholipid complex microemulsion and conventional microemulsion prepared before. Methods The chylomicron flow blocking approach was used to block lymphatic transport of the microemulsion, and the concentration of puerarin in plasma was determined by HPLC. Bioavailability of puerarin inblocking groups and non-blocking groups were compared to calculate the proportion of puerarin absorbed by lymphatic transport. Results The lymphatic transport of puerarin-phospholipid complex microemulsion was higher than that of conventional microemulsion, and the lymphatic translocation ratio was 51.3% and 40.6%, respectively. The AUC0-12 of puerarin-phospholipid complex microemulsion non-blocking and blocking groups were (5.489 ± 1.599) μg•h/mL and (2.673 ± 1.153) μg•h/mL, respectively; And AUC0-12 of puerarin routine microemulsion non-blocking and blocking groups were (4.158 ± 1.160) μg•h/mL and (2.478 ± 1.352) μg•h/mL, respectively. Conclusion The lymphatic transport of puerarin-phospholipid complex microemulsion can increase lymphatic transport efficiency, and AUC0-12 of which were higher than those of conventional microemulsion group.

Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake

Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration-time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (<0.01). The absorption rate constant () and the apparent permeability coefficient () for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values ofandof Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration () of the blocking model were significantly lower than those of the control model (<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.

A review on intestinal lymphatic drug transport / 中国药学杂志

OBJECTIVE: Available information on the background of the current state and advances of the intestinal lymph trans port of medicines were reviewed. Drug transported by the intestinal lymphatic system can avoid hepatic first-pass metabolism, increase the bioavalibitlty of the highly lipophilic drug, and it is of importance for immunomodulatory, anticancer and anti-infective drugs. METHODS: We conducted a systematic literature review of articles published recent years, analysis and summaries are made upon the advances and methods applied for the increase of the intestinal lymph transport. RESULTS AND CONCLUSION: Intestinal lymphatic transport can increase the bioavailability via a reduction in the first-pass metabolism and the possibility of specifically targeting drugs to regions of the lymphatics, thus it is very advantageous for drugs that are under significant first-pass metabolism. The present review embodies a brief background of the mechanism of access of drugs to the intestinal lymph, a discussion on the links between lipid absorption and transport of highly lipophilic drugs, and approaches for enhancing lymphatic drug transport. Finally, experimental models of the lymphatic transport are also discussed.