Meta-Analysis of Drug Delivery Approaches for Treating Intracellular Infections

Abstract

This meta-analysis aims to evaluate the trend, methodological quality and completeness of studies on intracellular delivery of antimicrobial agents. PubMed, Embase, and reference lists of related reviews were searched to identify original articles that evaluated carrier-mediated intracellular delivery and pharmacodynamics (PD) of antimicrobial therapeutics against intracellular pathogens in vitro and/or in vivo. A total of 99 studies were included in the analysis. The most commonly targeted intracellular pathogens were bacteria (62.6%), followed by viruses (16.2%) and parasites (15.2%). Twenty-one out of 99 (21.2%) studies performed neither microscopic imaging nor flow cytometric analysis to verify that the carrier particles are present in the infected cells. Only 31.3% of studies provided comparative inhibitory concentrations against a free drug control. Approximately 8% of studies, albeit claimed for intracellular delivery of antimicrobial therapeutics, did not provide any experimental data such as microscopic imaging, flow cytometry, and in vitro PD. Future research on intracellular delivery of antimicrobial agents needs to improve the methodological quality and completeness of supporting data in order to facilitate clinical translation of intracellular delivery platforms for antimicrobial therapeutics.

Nanocarriers for the delivery of antibiotics into cells against intracellular bacterial infection

“…lipids and macromolecules) for delivering antimicrobial adjuncts into cells to increase the intracellular concentration and antibacterial activity. 14,42…”

“…lipids and macromolecules) for delivering antimicrobial adjuncts into cells to increase the intracellular concentration and antibacterial activity. 14,42 Compared with traditional drugs, nanocarrier system has several advantages such as high cellular uptake efficiency, long circulation time, and targeting ability. 53 As shown in Fig.…”

“…In recent years, the effective delivery of antibiotics into cells based on nanotechnology for the enhancement of intracellular antibacterial activity has become a hot spot in anti-intracellular bacterial infection research. [12][13][14] Although there are many reviews of nanocarriers, most of the nanocarriers are used to deliver anti-tumor drugs, 15 genes 16 or CRISPR gene editing systems. 17 And those reported nanocarriers used to deliver antibiotics mainly focused on local delivery to improve drug concentration at the infection site 18 and overcoming bacterial envelope barrier to promote bacterial internalization of antibiotic.…”

Effective Treatments of UTI—Is Intravesical Therapy the Future?

“…The targeting of intracellular bacterial colonies in cases of recurrent UTI presents a considerably greater challenge [ 79 ]. To eradicate these pathogens, it is necessary to use an antibiotic with physicochemical properties that favour the transcellular route that directs the drug to/through the cytoplasmic compartment.…”

Minimum Information for Conducting and Reporting In Vitro Intracellular Infection Assays

“…One such challenge is the lack of reproducibility between published research findings, including insufficient reporting of important experimental parameters and outcomes that can guide the scientific community. A recent meta-analysis on drug delivery approaches for intracellular infection highlighted the inadequate methodological quality of published studies, impeding successful clinical translation of new and emerging therapeutics . Examples identified include insufficient evidence to confirm intracellular delivery of nanoparticles and unsatisfactory interpretation and comparison of efficacy results without inclusion of appropriate study controls (e.g., lacking comparison of antibacterial activity of novel formulation versus free antibiotic).…”