Ionic co-aggregates (ICAs) based oral drug delivery: Solubilization and permeability improvement.

Due to the overwhelming percentage of poorly water-soluble drugs, pharmaceutical industry is in urgent need of efficient approaches for solubilization and permeability improvement. Salts consisting of lipophilic fatty acid anions and hydrophilic choline cations are found to be surface active and able to form ionic co-aggregates (ICAs) in water. Choline oleate-based ICAs significantly enhance oral absorption of paclitaxel (PTX) as compared with cremophor EL-based micelles (MCs). Aggregation-caused quenching probes enable tracking of intact ICAs in in vivo transport and cellular interaction. Prolonged intestinal retention of ICAs than MCs implies stronger solubilizing capability in vivo. Ex vivo imaging of major organs and intestinal tracts suggests transepithelial transport of intact ICAs. Cellular studies support the enhanced absorption of PTX and transmembrane transport of intact ICAs. In conclusion, ICAs, consisting of lipophilic ions and hydrophilic counter-ions, are of great potential in delivery of poorly water-soluble drugs by enhancing solubility and permeability.

Ionic Liquids: Emerging Antimicrobial Agents.

Antimicrobial resistance has become a serious threat to global health. New antimicrobials are thus urgently needed. Ionic liquids (ILs), salts consisting of organic cations and anions with melting points less than 100°C, have been recently found to be promising in antimicrobial field as they may disrupt the bacterial wall and membrane and consequently lead to cell leakage and death. Different types of antimicrobial ILs are introduced in the review, including cationic, polymeric, and anionic ILs. Being the main type of the antimicrobial ILs, the review focuses on the structure and the antimicrobial mechanisms of cationic ILs. The quantitative structure-activity relationship (QSAR) models of the cationic ILs are also included. Increase in alkyl chain length and lipophilicity is beneficial to increase the antimicrobial effects of cationic ILs. Polymeric ILs are homopolymers of monomer ILs or copolymers of ILs and other monomers. They have great potential in the field of antibiotics as they provide stronger antimicrobial effects than the sum of the monomer ILs. Anionic ILs are composed of existing anionic antibiotics and organic cations, being capable to enhance the solubility and bioavailability of the original form. Nonetheless, the medical application of antimicrobial ILs is limited by the toxicity. The structural optimization aided by QSAR model and combination with existing antibiotics may provide a solution to this problem and expand the application range of ILs in antimicrobial field.

Enhanced transdermal delivery of curcumin nanosuspensions: A mechanistic study based on co-localization of particle and drug signals.

Nanosuspensions have received much attention in enhanced transdermal delivery. However, the corresponding mechanisms have not been clarified. In particular, whether nanosuspensions can directly penetrate across the stratum corneum (SC) and what is the transdermal route for the enhanced penetration. Therefore, curcumin (CUR) was adopted in this study as a model drug, while an aggregation-caused quenching (ACQ) probe was physically embedded in CUR nanosuspensions, i.e., the CUR hybrid nanosuspensions (CUR-HNSs), for bioimaging. The ACQ properties enable identification of intact CUR-HNSs. The co-localization of particle and CUR signals was exploited to outline the translocation profiles of intact nanosuspensions as well as the cargoes. Three sizes of CUR-HNSs are prepared, which are spherical and amorphous. CUR is poor in transdermal transport even in propylene glycol solution, which was enhanced by nanosuspensions. Although 400 nm CUR-HNSs present higher steady state flux than 140 nm and 730 nm ones, the cumulative amount of permeated CUR is yet less than 2% of the applied dose at 12 h. Co-localization of CUR and ACQ probe signals indicates that CUR-HNSs can infiltrate into the SC layer and accumulate in the hair follicles. The intact CUR-HNSs cannot enter into the skin. On the contrary, CUR molecules diffuse into the whole skin tissues following dissolution of CUR-HNSs in the SC and the hair follicles. In conclusion, nanosuspensions are advantageous for transdermal delivery of poorly permeable drugs by filtrate into the SC and accumulate in hair follicles.