Biodegradable functional polycarbonate micelles for controlled release of amphotericin B

Abstract

There is a pressing need for a novel and cost-effective delivery system to reduce the toxicity induced by the antifungal agent, amphotericin B (AmB). In this study, phenylboronic acid-functionalized polycarbonate/PEG diblock copolymers were used to fabricate micelles for improved AmB-micelle interaction via the manipulation of hydrogen-bonding, boronate ester bond, ionic and hydrophobic interactions. Compared to free AmB and Fungizone®, the resultant micellar systems displayed improved stability while reducing non-specific toxicities without a compromise in antifungal activity. These findings demonstrate the potential of biodegradable functional polycarbonate micellar systems as promising carriers of AmB for the treatment of systemic fungal infections.

Phenylboronic Acid Functionalized Polycarbonate Hydrogels for Controlled Release of Polymyxin B in Pseudomonas Aeruginosa Infected Burn Wounds

“…Synthesis of the PBC–PEG–PBC Polymer : The PBC–PEG–PBC polymer was prepared using previously reported protocol with slight modifications . Details of metal‐free organocatalytic ROP approach for the preparation of triblock copolymer (A–B–A) were given as an example.…”

Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary Aspergillosis

“…The AMB:DCH 1:1.5 polyaggregated formulation presented a small standard deviation when its particle size was studied, and this low variability should be attributed to the stabilizing effect of DCH by means of ionic interactions with AMB (5). Thus, in this AMB formulation, sodium deoxycholate acts as a stabilizing agent inhibiting particle growth, so the surfactant effect is critical in AMB nanoparticle systems (16,17).…”

“…Liposomal amphotericin B (LAMB) is the "gold standard" in aspergillosis therapy (1,3). Several studies have demonstrated that the large particle sizes of different AMB formulations are related to high nephrotoxicity (4)(5)(6)(7). Commercial dimeric deoxycholate (DCH)-amphotericin B (D-AMB) shows a high percentage of small particles (56.2 Ϯ 4.3 nm) and a small percentage of large particles (around 4.0 m) (6), the latter related to nephrotoxicity (4)(5)(6)(7).…”

“…Several studies have demonstrated that the large particle sizes of different AMB formulations are related to high nephrotoxicity (4)(5)(6)(7). Commercial dimeric deoxycholate (DCH)-amphotericin B (D-AMB) shows a high percentage of small particles (56.2 Ϯ 4.3 nm) and a small percentage of large particles (around 4.0 m) (6), the latter related to nephrotoxicity (4)(5)(6)(7). LAMB, the reference commercial formulation, with a polyaggregated AMB form, shows a small particle size (around 100 nm) that enhances antifungal efficacy and diminishes drug toxicity (8), while other lipid complexes marketed as Abelcet (ABLC) present polyaggregated AMB with a particle size of 1.6 to 11 m (7).…”

Biodegradable Antibacterial Polymeric Nanosystems: A New Hope to Cope with Multidrug‐Resistant Bacteria

“…Similarly, another pH responsive nanosystem based on the triblock copolymer of poly(ethylene glycol)‐ b ‐polycaprolactone‐ b ‐poly(β‐amino ester) (PEG‐ b ‐PCL‐ b ‐PAE) was reported, and the PAE blocks underwent charge switching from negative to positive due to the localized acidity caused by the bacterial infection, and triggered the release of encapsulated vancomycin to kill bacteria in subcutaneous infection sites . Afterward, many responsive and biodegradable micelle systems based on polycarbonates, polyurethane with disulfide linkages, biodegradable dendrimers, acid cleavable lipids, and polysaccharides have been reported as antibiotics carriers for the treatment of bacterial infections. Moreover, the co‐delivery of silver nanoparticles (AgNPs) and curcumin in the micelles fabricated by a diblock copolymer poly(aspartic acid)‐ b ‐poly(ε‐caprolactone) (PAsp‐ b ‐PCL) was also reported to enhance antibacterial efficacy …”