Intestinal lymphangiectasia: Understanding the bigger picture.

Intestinal lymphangiectasia (IL) is characterized by the dilation of intestinal lymphatic vessels, which can rupture and cause loss of lymph into the intestine. Due to the high content of proteins, lipoproteins, and lymphocytes in the intestinal lymph, loss of lymph might result in hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and lymphocytopenia. In addition, there may be a depletion of minerals, lipids, and fat-soluble vitamins. IL can be primary due to inherent malfunctioning of the lymphatic system, or secondly, a result of various factors that may hinder lymphatic drainage either directly or indirectly. This condition has emerged as a subject of significant clinical interest. Given that the intestinal lymphatic system plays an important role in the body's fluid homeostasis, adaptive immunity, nutrient and drug absorption, intestinal transport, and systemic metabolism, its dysfunction may have wider implications. Although primary IL is rare, with varied clinical features, complications, treatment response, and outcomes, secondary IL is more common than previously believed. The definitive diagnosis of IL requires endoscopic demonstration of whitish villi (which frequently resemble snowflakes) and histological confirmation of dilated lacteals in the small intestinal mucosa. Treatment of IL is challenging and involves dietary modifications, managing underlying medical conditions, and using medications such as sirolimus and octreotide. Recognizing its prevalence and diverse etiology is crucial for targeted management of this challenging medical condition. This article provides a comprehensive exploration of the clinical implications associated with IL. In addition, it offers valuable insights into critical knowledge gaps in the existing diagnostic and management landscape.

Effects of corn oil administered orally on conspicuity of ultrasonographic small intestinal lesions in dogs with lymphangiectasia.

Lymphangiectasia is one of the causes of protein-losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full-thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P < 0.05) and were best identified in dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal.

Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle.

Efficient delivery of highly lipophilic drugs or prodrugs to the mesenteric lymph nodes (MLN) can be achieved following oral administration with lipids. However, it remains unclear which specific MLN can be targeted and to what extent. Moreover, the efficiency of drug delivery to the retroperitoneal lymph nodes (RPLN) has not been assessed. The aim of this study was to assess the distribution of a highly lipophilic model drug cannabidiol (CBD), known to undergo intestinal lymphatic transport following administration with lipids, into specific MLN and RPLN in rats at various time-points post dosing. In vivo studies showed that at 2 h following administration, significantly higher concentrations of CBD were present in the region second from the apex of the MLN chain. From 3 h following administration, concentrations in all MLN were similar. CBD was also found at substantial levels in RPLN. This study demonstrates that drug concentrations in specific MLN are different, at least at the peak of the absorption process. Moreover, in addition to the MLN, the RPLN may also be targeted by oral route of administration, which may have further implications for treatment of a range of diseases.

Quality by design (QbD)-based fabrication of atazanavir-loaded nanostructured lipid carriers for lymph targeting: bioavailability enhancement using chylomicron flow block model and toxicity studies.

Atazanavir (ATV) is widely used as anti-HIV agent having poor aqueous solubility needs to modulate novel drug delivery system to enhance therapeutic efficiency and safety. The main objective of the present work was to fabricate ATV-loaded nanostructured lipid carriers (NLCs) employing quality by design (QbD) approach to address the challenges of bioavailability and their safety after oral administration. Herein, the main objective was to identify the influencing variables for the production of quality products. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (p < 0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, powder X-ray diffraction, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37 ± 1.03%) with a mechanism of Korsmeyer-Peppas model (r2 = 0.925, and n = 0.63). In vivo evaluation in Wistar rats showed significantly higher (p < 0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.