Surface modification of nano-drug delivery systems for enhancing antibiotic delivery and activity.

Rampant antimicrobial resistance calls for innovative strategies to effectively control bacterial infections, enhance antibacterial efficacy, minimize side effects, and protect existing antibiotics in the market. Therefore, to enhance the delivery of antibiotics and increase their bioavailability and accumulation at the site of infection, the surfaces of nano-drug delivery systems have been diversely modified. This strategy applies various covalent and non-covalent techniques to introduce specific coating materials that have been found to be effective against various sensitive and resistant microorganisms. In this review, we discuss the techniques of surface modification of nanocarriers loaded with antibacterial agents. Furthermore, saccharides, polymers, peptides, antibiotics, enzymes and cell membranes coatings that have been used for surface functionalization of nano-drug delivery systems are described, emphasizing current approaches for enhancing delivery, bioavailability, and efficacy of surface-modified antibacterial nanocarriers at infection sites. This article offers a critical overview of the potential of surface-modified antibacterial nanocarriers to overcome the limitations of conventional antibiotics in the treatment of bacterial infections. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Formulation of pH responsive multilamellar vesicles for targeted delivery of hydrophilic antibiotics.

Fight against antimicrobial resistance calls for innovative strategies that can target infection sites and enhance activity of antibiotics. Herein is a pH responsive multilamellar vesicles (MLVs) for targeting bacterial infection sites. The vancomycin (VCM) loaded MLVs had 62.25 ± 8.7 nm, 0.15 ± 0.01 and -5.55 ± 2.76 mV size, PDI and zeta potential, respectively at pH 7.4. The MLVs had a negative ZP at pH 7.4 that switched to a positive charge and faster release of the drug at acidic pH. The encapsulation efficiency was found to be 46.34 ± 3.88 %. In silico studies of the lipids, interaction suggested an energetically stable system. Studies to determine the minimum inhibitory concentration studies (MIC) showed the MLVs had 2-times and 8-times MIC against Staphylococcus aureus (SA) and Methicillin resistance SA respectively at physiological pH. While at pH 6.0 there was 8 times reduction in MICs for the formulation against SA and MRSA in comparison to the bare drug. Fluorescence-activated Cell Sorting (FACS) studies demonstrated that even with 8-times lower MIC, MLVs had a similar elimination ability of MRSA cells when compared to the bare drug. Fluorescence microscopy showed MLVs had the ability to clear biofilms while the bare drug could not. Mice skin infection models studies showed that the colony finding units (CFUs) of MRSA recovered from groups treated with MLVs was 4,050 and 525-fold lower than the untreated and bare VCM treated groups, respectively. This study demonstrated pH-responsive multilamellar vesicles as effective system for targeting and enhancing antibacterial agents.

A transferosome-loaded bigel for enhanced transdermal delivery and antibacterial activity of vancomycin hydrochloride.

Transdermal drug delivery is an attractive route of administration relative to other routes as it offers enhanced therapeutic efficacy. However, due to poor skin permeability of certain drugs, their application in transdermal delivery is limited. The ultra-deformable nature of transferosomes makes them suitable vehicles for transdermal delivery of drugs that have high molecular weights and hydrophilicity. However, their low viscosity, which leads to low contact time on the surface of the skin, has restricted their application in transdermal delivery. Therefore, this study aimed to deliver transferosomes loaded with a highly water-soluble and high molecular weight vancomycin hydrochloride (VCM-HCl) via a bigel for systemic delivery and treatment of microbial infections. VCM-HCl-loaded transferosomal formulations (TNFs) were prepared using a reverse-phase evaporation method and then loaded into a bigel. Both the TNFs and TNFs-loaded bigel (TNF-L-B) were characterized by a range of in vitro and ex vivo techniques. TNFs and TNF-L-B were tested for biosafety via the MTT assay and found to be biosafe. Prepared TNFs had sizes, zeta potential and entrapment efficiency of 63.02 ± 5.34 nm, -20.93 ± 6.13 mV and 84.48 ± 1.22% respectively. VCM-HCl release from TNF-L-B showed a prolonged release profile with 39.76 ± 1.6% after 24hrs when compared to bare VCM-HCl loaded in the bigel (74.81 ± 8.84%). Ex-vivo permeation of prepared TNF-L-B showed a higher permeation flux of 0.56 µg/cm2/h compared to the bare VCM-HCl-loaded bigel of 0.23 µg/cm2/h, indicating superior permeation and bioavailability of the drug. Additionally, the prepared TNF-L-B demonstrated improved antimicrobial activity. The TNF-L-B showed minimum inhibitory concentrations (MIC) of 0.97 µg/ml against Staphylococcus aureus (SA) and 1.95 µg/ml against methicillin-resistant SA (MRSA), which were 2-fold lower MIC values than the bare drug. The time-kill assay showed that both TNFs and TNF-L-B systems caused a 5.6-log reduction (100%) in MRSA compared to bare VCM-HCl after 24 hrs of incubation. Furthermore, as opposed to the bare VCM-HCl solution, the degree of biofilm reduction caused by TNFs (55.72%) and TNF-L-B (34.58%) suggests their dominance in eradicating MRSA biofilm. These findings indicate that TNF-L-B is a promising system for transdermal delivery of hydrophilic and high molecular weight drugs.