An update on oral drug delivery

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 transport-the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

Congenital chylothorax: a rare entity

Pleural effusions in a neonate are generally congenital in about one third of the cases and acquired in the remaining two thirds. Congenital isolated pleural effusion is rare. It has an incidence of approximately 1 in 12000 to 1 in 15000 pregnancies. Chylothorax is the most common cause of neonatal congenital pleural effusion. Incidence of congenital chylothorax is 1 in 8600 to 1 in 10000 deliveries with a male to female ratio of 2:1. It poses both a diagnostic as well as therapeutic challenge to the neonatologist. Authors hereby present a rare case of congenital chylothorax which was medically managed and discharged. The neonate responded well to octreotide and medium chain triglyceride (MCT)-diet and was discharged without any complications.

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.

Chylomicron Retention Disease: a Description of a New Mutation in a Very Rare Disease / 대한소아소화기영양학회지

Chylomicron retention disease, also known as Anderson's disease, is a rare hereditary hypocholesterolemic disorder, recessive inherited, characterized by nonspecific symptoms as abdominal distension, steatorrhea, and vomiting associated with failure to thrive. We describe a patient with failure to thrive, chronic diarrhea and steatorrhea who the diagnosis of chylomicron retention disease was established after several months of disease progression. The genetic study confirmed a homozygosity mutation in SAR1B gene, identifying a mutation never previous described [c.83_84delTG(p.Leu28Argfs*7)]. With this case report the authors aim to highlight for this very rare cause of failure to thrive and for the importance of an attempting diagnosis, in order to start adequate management with low fat diet supplemented with fat-soluble vitamins, reverting the state of malnutrition and avoiding possible irreversible and desvantating complications.

Intestinal lymphatic transport of matrine from two self-nanoemulsifying drug delivery systems assessed by triple single pass intestinal perfusion approach in rats / 中国药学杂志

OBJECTIVE: To investigate the differences of two matrine (MA) self-nanoemulsifying drug delivery systems (SNEDDS) in intestinal lymphatic transport. METHODS: Triple single pass intestinal perfusion model (T-SPIP) was established to study the intestinal absorption kinetics of MA in different absorption segments of rats with chylomicron flow blocking approach using colchicine as the blocker. The concentration of MA in the perfustae was measured by HPLC. RESULTS: The two SNEDDSs had regular spherical surface and narrow particle size distribution. MA showed high Peff. The phospholipid complex formulation (MPC-SN) exhibited higher intestinal lymphatic transport especially in distal ileum, and it was influenced more significantly by the chylomicron flow blocker in distal ileum compared to in proximal jejunum and mid-small intestine. CONCLUSION: SNEDDS can improve the absorption of MA by intestinal lymphatic transport. MPC-SN might be easier to be absorbed via lymphatic transport because of its high lipophilicity and small particle size.

Lipoproteínas remanentes aterogénicas en humanos / Atherogenic lipoprotein remnants in humans

La lipoproteínas remanentes (RLPs) son el producto de la lipólisis de los triglicéridos transportados por las lipoproteínas de baja densidad (VLDL) de origen hepático e intestinal y de los quilomicrones intestinales. Dicha lipólisis es catalizada por la lipoproteína lipasa y se produce en pasos sucesivos, de manera que los productos son heterogéneos. Su concentración plasmática en ayunas es pequeña en pacientes normolipémicos y aumenta en el estado post-prandial. Las alteraciones genéticas en subtipos de su componente Apo-E aumentan notablemente su concentración plasmática y producen el fenotipo de disbetalipoproteinemia. Se las considera aterogénicas porque injurian el endotelio, sufren estrés oxidativo, son captadas por los macrófagos en el subendotelio vascular y generan las células espumosas que son precursoras de ateromas. Su origen metabólico, como productos de varios tipos de lipoproteínas, explican su estructura heterogénea, sus concentraciones plasmáticas variables y las dificultades metodológicas que dificultan su inclusión en el perfil lipoproteico como parte de los estudios epidemiológicos. Los últimos avances en los estudios metabólicos y la actualización de su papel clínico, justifican una revisión de los conocimientos actuales.

Remnant lipoproteins (RLPs) are the lipolytic product of triglycerides transported by very low density lipoproteins (VLDL) of hepatic and intestinal origin and intestinal chylomicrons. Lipoprotein lipase activity hydrolyse triglycerides in several steps, producing heterogeneous particles. Fasting plasma concentration in normolipidemic subjects is low, but it increases in post-prandial states. Genetic alterations in Apo-E subtypes increases RLPs plasma concentration and produce dyslipoproteinemia phenotype. RLPs atherogenicity depends on their role as endothelial injuring factors, their impaired recognition by lipoprotein receptors, and their susceptibility to oxidative stress. They also promote the circulation of molecular adhesion molecules, the internalization in subendothelial macrophages via scavenger receptors and the accumulation in foam cells, all of them early mechanisms of atheromatosis. RLPs metabolism has been a subject of controversial studies. Their origin from different lipoproteins may explain their structural heterogeneity, therefore increasing the methodological difficulties to include RLPs in the atherogenic lipoprotein profile in the epidemiological studies of the field. Last advances on metabolism of RLPs and their emergent clinical role justifies an up dated revision of RLPs.