Enhanced oral delivery of insulin via the colon-targeted nanocomposite system of organoclay/glycol chitosan/Eudragit®S100.

This study aimed to develop a ternary nanocomposite system of organoclay, glycol-chitosan, and Eudragit®S100 as an effective colon targeted drug delivery carrier to enhance the oral absorption of insulin. A nanocomplex of insulin and aminoclay was prepared via spontaneous co-assembly, which was then coated with glycol-chitosan and Eudragit S®100 (EGAC-Ins). The double coated nanocomplex, EGAC-Ins demonstrated a high entrapment efficiency of greater than 90% and a pH-dependent drug release. The conformational stability of insulin entrapped in EGAC-Ins was effectively maintained in the presence of proteolytic enzymes. When compared to a free insulin solution, EGAC-Ins enhanced drug permeability by approximately sevenfold in Caco-2 cells and enhanced colonic drug absorption in rats. Accordingly, oral EGAC-Ins significantly reduced blood glucose levels in diabetic rats while the hypoglycemic effect of an oral insulin solution was negligible. In conclusion, EGAC-Ins should be a promising colonic delivery system for improving the oral absorption of insulin.

Ternary nanocomposite carriers based on organic clay-lipid vesicles as an effective colon-targeted drug delivery system: preparation and in vitro/in vivo characterization.

This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system.

Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery.

Advancements in biotechnology and protein engineering expand the availability of various therapeutic proteins including vaccines, antibodies, hormones, and growth factors. In addition, protein drugs hold many therapeutic advantages over small synthetic drugs in terms of high specificity and activity. This has led to further R&D investment in protein-based drug products and an increased number of drug approvals for therapeutic proteins. However, there are many biological and biopharmaceutical obstacles inherent to protein drugs including physicochemical and enzymatic destabilization, which limit their development and clinical application. Therefore, effective formulations of therapeutic proteins are needed to overcome the various physicochemical and biological barriers. In current medical practice, protein drugs are predominantly available in injectable formulations, which have disadvantages including pain, the possibility of infection, high cost, and low patient compliance. Consequently, non-invasive drug delivery systems for therapeutic proteins have gained great attention in the research and development of biomedicines. Therefore, this review covers the various formulation approaches to optimizing the delivery properties of protein drugs with an emphasis on improving bioavailability and patient compliance. It provides a comprehensive update on recent advancements in nanotechnologies with regard to non-invasive protein drug delivery systems, which is also categorized by the route of administrations including oral, nasal, transdermal, pulmonary, ocular, and rectal delivery systems.

Piperine-mediated drug interactions and formulation strategy for piperine: recent advances and future perspectives.

INTRODUCTION: Piperine has various pharmacological effects and can modulate the functional activity of metabolic enzymes and drug transporters. Consequently, there is a great interest in the application of piperine as an alternative medicine or bioavailability enhancer. Areas covered: This review deals with the effects of piperine on metabolizing enzymes and drug transporters. It provides the readers with an update on transporter-mediated and also metabolic enzyme-mediated piperine-drug interactions, with emphasis on its in vivo implications. This article also encompasses recent advances in the formulation approaches and technologies for optimizing the delivery of piperine. Expert opinion: Piperine can influence the pharmacokinetics of coadministered drugs, which may result in a therapeutically beneficial or adverse effect. Given that piperine inhibits or stimulates the activity of metabolic enzymes and transporters depending on the treatment conditions, the clinical significance of piperine-drug interactions should be assessed by varying the dose, dosing frequency, and the duration of treatment. In particular, better understanding the clinical relevance of piperine-drug interactions based on long-term assessments will provide a strong basis for the feasibility and applicability of piperine as a bioenhancer or a health-promoting agent. The development of effective formulations is also critical to facilitate the therapeutic applications of piperine.