Bile acids and bile acid derivatives: use in drug delivery systems and as therapeutic agents.

INTRODUCTION: Bile acids are biological surfactants and signaling molecules with important paracrine and endocrine functions. The enterohepatic organotropism of bile acids turns these facial amphiphiles into attractive drug delivery systems for selective drug targeting to the liver or to enhance drug bioavailability by improving intestinal absorption and metabolic stability. AREAS COVERED: Bile acid-based amphiphiles, in the form of mixed micelles, bilosomes, drug conjugates and hybrid lipid-polymer nanoparticles are critically discussed as delivery systems for anticancer drugs, antimicrobial agents and therapeutic peptides/proteins, including vaccines. Therapeutic applications of bile acid derivatives as cytotoxic and neuroprotective agents are also addressed. EXPERT OPINION: Bile acids play an important role in modulating cancer therapy and novel derivatives with cytotoxic activity not restricted to the gastrointestinal tract can be expected. Selective toxicity targeting the bacterial membrane remains an attractive area of research for further development of bile acid-based bactericidal agents. On the other hand, the neuroprotective properties of some bile acids offer therapeutic potential in neurodegenerative disorders. Bile acid-based nanoparticles are also a growing research area due to the unique characteristics and tunable properties of these nanosystems. Therefore, multifaceted pharmaceutical and biomedical applications of bile salts are to be expected in the near future.

Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B.

Lipoamino acid-based micelles have been developed as delivery vehicles for the hydrophobic drug amphotericin B (AmB). The micellar solubilisation of AmB by a gemini lipoamino acid (LAA) derived from cysteine and its equimolar mixtures with the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC), as well as the aggregation sate of the drug in the micellar systems, was studied under biomimetic conditions (phosphate buffered-saline, pH 7.4) using UV-vis spectroscopy. Pure surfactant systems and equimolar mixtures were characterized by tensiometry and important parameters were determined, such as critical micelle concentration (CMC), surface tension at the CMC (γCMC), maximum surface excess concentration (Γmax), and minimum area occupied per molecule at the water/air interface (Amin). Rheological behaviour from viscosity measurements at different shear rates was also addressed. Solubilisation capacity was quantified in terms of molar solubilisation ratio (χ), micelle-water partition coefficient (KM) and Gibbs energy of solubilisation (ΔGs°). Formulations of AmB in micellar media were compared in terms of drug loading, encapsulation efficiency, aggregation state of AmB and in vitro antifungal activity against Candida albicans. The LAA-containing micellar systems solubilise AmB in its monomeric and less toxic form and exhibit in vitro antifungal activity comparable to that of the commercial formulation Fungizone.

Clinical Efficiency of Two Sequences of Orthodontic Wires to Correct Crowding of the Lower Anterior Teeth.

This study compared time to correction of mandibular anterior crowding using two arch wire sequences, one with conventional nickel-titanium (NiTi) arch wires and the other with conventional and NiTi heat-activated arch wires. Twenty-two boys and girls (mean age: 16.68 ± 2.66) with moderate crowding (3-6 mm) were assigned randomly to one of two groups and followed up for five months (six assessments) when arch wires were changed. Time to crowding correction was analyzed statistically using the Kaplan-Meier method. Data were collected during the five-month follow-up, and time to correction was compared between groups using the log rank test. At the end of follow-up, mandibular crowding was corrected in 100% of the cases in the group treated with the sequence that included NiTi heat-activated arch wires, whereas about 30% of those treated with NiTi arch wires were not completely corrected. There was a significant difference in time to complete treatment between groups (log rank = 5.996; p < 0.05). In the group treated with the sequence that included heat-activated wires, alignment and leveling of mandibular anterior teeth were completed earlier than in the group treated only with conventional NiTi arch wires. Clinical trial registration is found at RBR-7g5zng.