Health care-associated infections: Controlled delivery of cationic antiseptics from polymeric excipients.

Nowadays, the treatment of health care-associated infections represents a serious issue, due to the increasing number of bacterial strains resistant to traditional antibiotics. The use of antiseptics like quaternary ammonium salts and biguanides is a viable alternative to face these life-threatening infections. However, their inherent toxicity as well as the necessity of providing a sustained release to avoid the formation of pathogen biofilms are compelling obstacles towards their assessment in the hospitals. Within this framework, the role of polymeric drug delivery systems is fundamental to overcome the aforementioned problems. Biocompatibility, biodegradability and excipient-drug interactions are crucial properties determining the efficacy of the formulation. In this work, we provide an in-depth analysis of the polymer drug delivery systems that have been developed or are under development for the sustained release of positively charged antiseptics, highlighting the crucial characteristics that allowed to achieve the most relevant therapeutic effects. We reported and compared natural occurring polymers and synthetic carriers to show their pros and cons and applicability in the treatment of health care-associated infections. Then, the discussion is focused on a particularly relevant class of materials adopted for the scope, represented by polyesters, which gave rise, due to their biodegradability, to the field of resorbable drug delivery devices. Finally, a specific analysis on the effect of the polymer functionalization over the formulation performances for the different types of polymeric carriers is presented.

Concentration of Polymer Nanoparticles Through Dialysis: Efficacy and Comparison With Lyophilization for PEGylated and Zwitterionic Systems.

Biodegradable polymeric nanoparticles (NPs) are attracting increasing attention as carriers for drug delivery. However, one of the main factors limiting their transition to the market is their premature degradation and release of the payload during the storage. Therefore, for increasing the formulation shelf-life, the removal of water is of paramount importance. In this work, we synthesized both polyethylene glycol (PEG)-stabilized and zwitterionic NPs via Reversible Addition Fragmentation Chain Transfer (RAFT) Polymerization. We demonstrated that lyophilization leads the PEGylated NPs to irreversible aggregation, while the stability of the zwitterionic NPs was preserved only using a cryoprotectant. Therefore, we developed an alternative method for the NP concentration, based on the dialysis against a concentrated PEG solution. This method was optimized in terms of concentration factor (Fc), the ratio between the final and initial NP concentration, by acting on the PEG concentration in the dialysis medium, on its volume and on the initial NP concentration. With this approach, Fc up to 40 can be achieved in less than 10 h, preserving the possibility of redispersing the NPs to their original particle size distribution. Therefore, the dialysis proposed herein is a valuable alternative to lyophilization for the concentration of polymer NPs preserving their stability.

Zwitterionic Polyester-Based Nanoparticles with Tunable Size, Polymer Molecular Weight, and Degradation Time.

Biodegradable polymer nanoparticles are an important class of materials used in several applications for their unique characteristics. In particular, the ones stabilized by zwitterionic materials are gaining increased interest in medicine as alternative to the more common ones based on poly(ethylene glycol) thanks to their superior stability and ability to avoid both the accelerated blood clearance and allergic reactions. In this work, a novel class of zwitterionic based NPs has been produced, and a method to independently control the nanoparticle size, degradation time, and polymer molecular weight has been developed and demonstrated. This has been possible by the synthesis and the fine-tuning of zwitterionic amphiphilic block copolymers obtained via the combination of ring-opening polymerization and reversible addition-fragmentation chain transfer polymerization. The final results showed that when two block copolymers contain the same number of caprolactone units, the one with longer oligoester lateral chains degrades faster. This phenomenon is in sharp contrast with the one seen so far for the common linear polyester systems where longer chains result in longer degradation times, and it can be used to better tailor the degradation behavior of the nanoparticles.