Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines

Abstract

Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines have poor performance after oral administration due to poor solubility or degradation in the gastrointestinal tract (GIT). Though, vesicular carriers exemplified by liposomes or niosomes can protect the entrapped agent to a certain extent from degradation. Nevertheless, the harsh GIT environment exemplified by low pH, presence of bile salts and enzymes limits their capabilities by destabilizing them. In response to that, more resistant bile salts-containing vesicles (BS-vesicles) were developed by inclusion of bile salts into lipid bilayers constructs. The effectiveness of orally administrated BS-vesicles in improving the performance of vesicles has been demonstrated in researches. Yet, these attempts did not gain considerable attention. This is the first review that provides a comprehensive overview of utilizing BS-vesicles as a promising pharmaceutical carrier with a special focus on their successful applications in oral delivery of therapeutic macromolecules and vaccines. Insights on the possible mechanisms by which BSvesicles improve the oral bioavailability of the encapsulated drug or immunological response of entrapped vaccine are explained. In addition, methods adopted to prepare and characterize BSvesicles are described. Finally, the gap in the scientific researches tackling BS-vesicles that needs to be addressed is highlighted.

Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam

“…However, the increase in bile salts concentration concurrently increases drug solubility in the dispersion medium due to the possible existence of mixed micelles, thereby compromising the EE% (Mahmood et al, 2014;Niu et al, 2014). Furthermore, the fluidizing effect of bile salts on the lipid bilayers of the vesicles, at high concentration, could also lead to the leakage of the entrapped drug (Niu et al, 2011;Aburahma, 2014).…”

“…Different researches have confirmed the potential of employing bilosomes to enable successful oral delivery of vaccines (Aburahma, 2014;Mann et al, 2006;Shukla et al, 2008Shukla et al, , 2011Jain et al, 2014;Wilkhu et al, 2013). Bile salts present in the lipid bilayers of bilosomes make them more resistant against gastro-intestinal (GI) bile salts and enzymes, therefore, offer protection for the entrapped vaccine against the hostile environment of the GI tract (Aburahma, 2014;Mann et al, 2006;Shukla et al, 2008Shukla et al, , 2011. Although, bilosomes have not been yet investigated for transdermal drug delivery, their nano-sized vesicles associated with the presence of surfactants and bile salts in their constructs suggest promising prospects for employing them transdermally.…”

Preparation and Optimization of In Situ Gel Loaded with Rosuvastatin-Ellagic Acid Nanotransfersomes to Enhance the Anti-Proliferative Activity

“…The presence of such EA weakens the bonds between phospholipids molecules and imparts the property of elasticity onto transferases making them ultra deformable vesicles. Transferosomes have several advantages that make them successful vesicular drug delivery systems, including (a) being biodegradable and biocompatible with human body, and (b) the ability of EA to solubilize and stabilize poorly soluble drugs owing to their surface activity, low toxicity, enhanced tissue targeting capacity, and ability to obtain prolonged drug release [10][11][12]. RO, also known as "superstatin," is the most effective antihyperlipidemic agent in the statins family.…”

Multifaceted applications of bile salts in pharmacy: an emphasis on nanomedicine

“…35 Oral bilosome preparation could induce significant cell-mediated responses against synthetic peptides comparable to those obtained by systemic immunization. 39,75,76 Oral hydrophobic drugs Amenability of bilosomes for enhancing oral availability was not confined to hydrophilic drugs entrapped in hydrophilic core. 77 Few hydrophobic actives have been successful candidates for bilosomes as well where the drug would be entrapped in the PL bilayer of the vesicles.…”