Old drug, new wrapping − A possible comeback for chloramphenicol?

Abstract

The antimicrobial drug chloramphenicol (CAM) exhibits activity against resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). However, its use has been limited due to its toxicity. As the threat of antibiotic resistance continues to grow, a promising approach might be to increase the use of historical antimicrobial agents that demonstrate clinical efficacy, but are hampered by toxicity. We therefore aimed to prepare a liposome-in-hydrogel system for dermal delivery of CAM. Chitosan (CS) was used as the hydrogel vehicle due to its antimicrobial activity and excellent biocompatibility. All critical preparation steps were carried out by dual centrifugation (DC). The DC-method proved to be fast and simple, and organic solvents were avoided in all processing steps. Liposomes with high drug entrapment (49-56%), low polydispersity and a size of approximately 120nm were produced. Mixing of liposomes into CS-hydrogel by DC produced a homogenous liposomes-in-hydrogel system. Bioadhesive properties were good and comparable to plain CS-hydrogel formulations. Ex vivo permeation studies using pig skin indicated a sustained release of CAM and limited skin permeation. The in vitro antimicrobial activity of CAM in the new liposome-in-hydrogel formulation was similar or better as compared to CAM in solution. Thus, the new formulation was considered highly promising.

Bacteria From the Multi-Contaminated Tinto River Estuary (SW, Spain) Show High Multi-Resistance to Antibiotics and Point to Paenibacillus spp. as Antibiotic-Resistance-Dissemination Players

“…The percentage of Cc R -isolates reached up to 50% only for Pseudomonas. These low levels of resistants may be a consequence of the limited use of Cc because of its toxicity (Ingebrigtsen et al, 2017); and, therefore, the existence of low selective pressure for this antibiotic in the environment. It has been shown that Rp R in pathogenic bacteria has a high metabolic cost, which significantly affects the fitness of the bacteria making their ARGs uncommon (Hall et al, 2011).…”

Liposomes‐in‐Chitosan Hydrogels: Challenges and Opportunities for Biomedical Applications

“…Preliminary in vivo results confirmed that the corresponding delivery system based on CS hydrogels enhanced wound healing and its efficiency was comparable to commercially available antibiotic drugs after 28 days of treatment. 49 The versatility of CS hydrogels has been also studied by incorporating other antimicrobial drugs in form of liposomes like chloramphenicol (CAM) in order to find effective treatments against drug-resistant pathogens (163). Liposomes were prepared from the dual centrifugation (DC) method, which involved the lipid film hydration (egg lecithin, 80 % PC) with a mixture of propylene glycol and distilled water (164) The direct encapsulation of therapeutic molecules into hydrogels can lead to uncontrolled release of the drug (burst release) and thus produce certain toxicity at the site of action.…”

Advancements on the molecular design of nanoantibiotics: current level of development and future challenges

“…The formulation of chloramphenicol in liposomes was recently proposed as an easy manner to overcome problems associated with the toxicity of the antibiotic. 32 Li et al showed that a liposomal co-delivery of daptomycin and clarithromycin is highly effective and less toxic for the treatment of methicillin-resistant S. aureus infections in the presence of only one-thirtieth of the concentration required in liposomes containing daptomycin only (Fig. 3A).…”