Improved Bioavailability of Poorly Soluble Drugs through Gastrointestinal Muco-Adhesion of Lipid Nanoparticles

Gastrointestinal absorption remains indispensable in the systemic delivery of most drugs, even though it presents several challenges that, paradoxically, may also provide opportunities that can be exploited to achieve maximal bioavailability. Drug delivery systems made from nanoparticle carriers and especially, lipid carriers, have the potential to traverse gastrointestinal barriers and deploy in the lymphatic pathway, which aptly, is free from first pass via the liver. Several poorly soluble drugs have presented improved systemic bioavailability when couriered in lipid nanoparticle carriers. In this review, we propose an additional frontier to enhancing the bioavailability of poorly soluble drugs when encapsulated in lipid nano-carriers by imparting muco-adhesion to the particles through application of appropriate polymeric coating to the lipid carrier. The combined effect of gastrointestinal muco-adhesion followed by lymphatic absorption is a promising approach to improving systemic bioavailability of poorly soluble drugs following oral administration. Evidence to the potential of this approach is backed-up by recent studies within the review.

Lymphatic Drug Transport and Associated Drug Delivery Technologies: A Comprehensive Review

Abstract:: Lymphatic system is the secondary circulation system of the human body, after the systemic circulation. Various problems, including first-pass metabolism through oral administration of medicines, can be resolved by lymphatic targeting. Lymphatic absorption has been explored in detail and studies reveal the improved bioavailability of medicines. In the case of cancer, AIDS, and various other health problems, lymphatic targeting has been focused on due to the fact that lymph nodes are involved greatly in tumor metastasis. This article reviews the lymphatic absorption and its exploration in the treatment of various health problems. The physiology of the lymphatic system, the mechanisms of absorption, and the various formulation systems suitable for lymphatic absorption have been discussed. Some recent novel approaches like hydrodynamically driven device (HDD) and carbon nanotubes for lymphatic delivery have also been appraised.

Quetiapine fumarate loaded nanostructure lipid carrier for enhancing oral bioavailability: Design, development and pharmacokinetic assessment

Aim: The study aimed at developing and characterizing nanostructure lipid carriers (NLC) of Quetiapine fumarate (QF) by Design of Experiment (DoE) for enhancement of bioavailability. Background:QF, an anti-psychotic drug, has oral bioavailability of 9% due to hepatic first pass metabolism necessitating use of high doses. Its side effects are dose related and enhancement in bioavailability would result in minimization of side effects. Objective: The objective of the study was enhancement of bioavailability of NLC of QF by preferential lymphatic uptake. Methods: Hot emulsification-ultrasonication was the method of formulation using PrecirolATO5 and Oleic acid as solid and liquid lipid respectively. Poloxamer188 and Phospholipon90G were used as surfactant and stabilizer respectively. Solid:liquid lipid ratio and Phospholipon90G amount were independent variables and percent entrapment efficiency (%EE), particle size (PS) dependent variables during optimization by Central Composite Design. Results: The optimized formulation showed %EE of 77.21%, PS of 140.2nm and surface charge of -19.9mV. Higuchi kinetic model was followed during in-vitro release. TEM revealed spherical, smooth nanoparticles. X-ray diffraction study con-firmed presence of drug in amorphous state in NLC. Pharmacokinetic study in rats showed AUC0-∞ of QF-NLC to be 3.93 times that of QF in suspension suggesting significant enhancement in bioavailability. An increase in AUC0-∞ in cyclo-heximide untreated rats group of QF loaded NLC by 2.43 times ascompared to cycloheximide treated group, confirmed lymphatic absorption of QF-NLC. Conclusion: The results validated DoE as an appropriate tool for developing QF loaded NLC and proved NLC to be a promising delivery system for enhancement of oral bioavailability of QF.

In vitrolipolysis and lymphatic absorption ofn-3 long-chain PUFA in the rat: influence of the molecular lipid species as carrier

The aim of this work was to study the bioavailability of fatty acids (FA), focusing onn-3 long-chain (LC) PUFA, carried by different molecular lipid species, that is, phospholipids (PL) or TAG, with three formulations based on fish oils or marine PL, providing a similarn-3 LC PUFA amount. The digestive lipolysis was first assessed using anin vitroenzymatic model. Then, intestinal absorption and enterocyte metabolism were investigatedin vivo, on male Wistar rats through lymph lipid analysis. Thein vitroresults showed that the release ofn-3 LC PUFA from lipolysis was increased by 48 % when FA were provided as PL rather than TAG. Thein vivoresults demonstrated that EPA and DHA from both TAG and PL were similarly absorbed and incorporated into lymph lipids. However, DHA was mainly distributed at thesn-1/3 positions of lymph TAG when provided as marine PL, whereas it was equally distributed at the three positions with marine TAG. On the whole, even if the molecular lipid species ofn-3 LC PUFA did not greatly modify thein vivodigestion and absorption steps, it modulated the rearrangement of DHA on the glyceride positions of the lymph TAG, which may further impact the DHA metabolic fate and tissue accretion. Consequently, the present study has provided data which may be used to formulate lipid diets rich in DHA in the context of an insufficient consumption ofn-3 PUFA in Western countries.

Alterations of peritoneal transport characteristics in dialysis patients with ultrafiltration failure: tissue and capillary components

BackgroundUltrafiltration failure (UFF) in peritoneal dialysis (PD) patients is due to altered peritoneal transport properties leading to reduced capacity to remove excess water. Here, with the aim to establish the role of local alterations of the two major transport barriers, peritoneal tissue and capillary wall, we investigate changes in overall peritoneal transport characteristics in UFF patients in relation to corresponding local alterations of peritoneal tissue and capillary wall transport properties.MethodsSix-hour dwell studies using 3.86% glucose solutions and radioisotopically labelled serum albumin added to dialysate as a volume marker were analysed in 31 continuous ambulatory PD patients, 20 with normal ultrafiltration (NUF) and 11 with UFF. For each patient, the physiologically based parameters were evaluated for both transport barriers using the spatially distributed approach based on the individual intraperitoneal profiles of volume and concentrations of glucose, sodium, urea and creatinine.ResultsUFF patients as compared with NUF patients had increased solute diffusivity in both barriers, peritoneal tissue and capillary wall, decreased tissue hydraulic conductivity and increased local lymphatic absorption and functional decrease in the fraction of the ultra-small pores. This resulted in altered distribution of fluid and solutes in the peritoneal tissue, and decreased penetration depths of fluid and solutes into the tissue in UFF patients.ConclusionsMathematical modelling using a spatially distributed approach for the description of clinical data suggests that alterations both in the capillary wall and in the tissue barrier contribute to UFF through their effect on transport and distribution of solutes and fluid within the tissue.