Oral budesonide treatment for protein-losing enteropathy in Fontan-palliated patients.

Protein-losing enteropathy (PLE) is a rare complication of Fontan palliation associated with significant morbidity and mortality. It is characterized by the loss of serum proteins into the intestinal lumen, and its pathophysiology likely involves enteral inflammation. Budesonide, an oral steroid, is an attractive treatment option because of its potent enteral activity and minimal systemic side effects. A single-center, retrospective review of Fontan-palliated PLE patients treated with oral budesonide for 6 months or longer was performed. The patient characteristics reviewed were demographics, anatomic diagnosis, budesonide treatment (dose and duration), other medications and therapeutic interventions, hospitalizations, serum albumin levels, medical complications, and patient status at the time of follow-up assessment. The study enrolled 10 patients representing 228 patient-months of on-therapy follow-up evaluation. Serum albumin levels increased after initiation of budesonide for 90% of the patients, and clinical evidence of fluid overload improved for 60% of them. Symptomatic improvement was reported in 80% of the cases. During the treatment period, 50% of the patients met the primary end point of death or cardiac transplantation. In this series of PLE patients, oral budesonide therapy was associated with significant symptomatic improvement and sustained increases in serum albumin. However, budesonide therapy may not alter the long-term outcome for patients with advanced PLE.

The twofold advantage of the amorphous form as an oral drug delivery practice for lipophilic compounds: increased apparent solubility and drug flux through the intestinal membrane.

The purposes of this study were to assess the efficiency of different nifedipine amorphous solid dispersions (ASDs) in achieving and maintaining supersaturation and to investigate the solubility-permeability interplay when increasing the apparent solubility via ASD formulations. Spray-dried ASDs of nifedipine in three different hydrophilic polymers, hydroxypropyl methylcellulose acetate succinate (HPMC-AS), copovidone, and polyvinylpyrrolidone (PVP), were prepared and characterized by powder X-ray diffraction and differential scanning calorimetry. The ability of these formulations to achieve and maintain supersaturation over 24 h was assessed. Then, nifedipine's apparent intestinal permeability was investigated as a function of increasing supersaturation in the parallel artificial membrane permeability assay model and in the single-pass rat intestinal perfusion model. The efficiency of the different ASDs to achieve and maintain supersaturation of nifedipine was found to be highly polymer dependent; while a dispersion in HPMC-AS enabled supersaturation 20× that of the crystalline aqueous solubility, a dispersion in copovidone enabled 10×, and PVP allowed supersaturation of only 5× that of the crystalline solubility. Nifedipine flux across the intestine from supersaturated solutions was increased, and the apparent intestinal permeability was constant, irrespective of the degree of supersaturation or the polymer being used. In conclusion, while with other solubility-enabling approaches (e.g., surfactants, cyclodextrins, cosolvents), it is not enough to increase the apparent solubility, but to strike the optimal solubility-permeability balance, which limits the chances for successful drug delivery, the amorphous form emerges as a more advantageous strategy, in which higher apparent solubility (i.e., supersaturation) will be readily translated into higher drug flux and overall absorption.

New targeting strategies in drug therapy of inflammatory bowel disease: mechanistic approaches and opportunities.

INTRODUCTION: Inflammatory bowel disease (IBD) is an exceptional scenario with regard to drug targeting, as oral administration has the potential to deliver the drug directly to the site(s) of action. Consequently, retention of the drug within the intestinal lumen and tissue, rather than systemic absorption, is frequently desirable. AREAS COVERED: In this article, the traditional drug-delivery strategies used in IBD are briefly summarized. These include rectal dosage forms and oral systems that target the lower intestine/colon by pH-, time-, microflora-, and pressure-dependent mechanisms. Then, the article offers an updated overview of recently developed delivery systems aimed to achieve maximal drug concentrations in the inflamed intestinal tissues with minimal systemic side effects. These include antibodies, small molecules, Janus kinase inhibitors, particulate carrier systems, anti-inflammatory peptides, gene therapy, and transgenic bacteria. The various approaches are reviewed, and the challenges that still remain to be overcome are discussed. EXPERT OPINION: The molecular revolution of the past decade profoundly influenced the treatment and management of IBD. In the coming years, this trend is expected to continue. Yet, many challenges are still ahead. A strong collaborative effort by experts from different fields is encouraged and necessary to maximize our success in IBD drug targeting.