Enhancement in Site-Specific Delivery of Chloramphenicol Using Bacterially Sensitive Microparticle Loaded Into Dissolving Microneedle: Potential For Enhanced Effectiveness Treatment of Cellulitis

Abstract

One of the biggest challenges in infectious disease treatment is the existence of bacterial infections in underskin wound tissue, such as cellulitis. Compared to other treatments, it is harder for antibacterial drugs to penetrate the physical barrier on the affected skin with a nonspecific target, making conventional therapy for cellulitis infection more difficult and considered. In this novel research, we pioneer a combined strategy of dissolving microneedles (MNs) and bacteria-sensitive microparticles (MPs) for enhanced penetration and targeted delivery of chloramphenicol (CHL) to the infection site specifically. The polycaprolactone polymer was used to make MPs because of its sensitivity to bacterial enzyme stimuli. The best microparticle formulation was discovered and optimized using the Design–Expert application. Furthermore, this study evaluated the antibacterial activity of MPs in vitro and in vivo on the mutant Drosophila larval infection model. This strategy shows improvement in the antibacterial activity of MPs and higher retention duration compared to conventional cream formulation, and the inclusion of these MPs into dissolving MNs was able to greatly improve the dermatokinetic characteristics of CHL in ex vivo evaluation. Importantly, the antimicrobial efficacy in an ex vivo infection model demonstrated that, following the use of this strategy, bacterial bioburdens decreased by up to 99.99% after 24 h. The findings offered a proof of concept for the enhancement of CHL dermatokinetic profiles and antimicrobial activities after its preparation into bacteria-sensitive MPs and distribution by MNs. Future research should investigate in vivo effectiveness in an appropriate animal model.

The Effect of Bay Leaf (Syzygium Polyanthum) Extract Hand Washing Liquid Soap Preparation on The Growth of Escherichia Coli Bacteria in Vitro

“…The results of the antibacterial inhibition test from the liquid hand washing soap sample obtained the average diameter of the inhibition zone at each concentration; namely a 3% concentration of 8.27 mm, 6% concentration of 10.55 mm, and 9% concentration of 11.16 mm and the soap base control has no inhibition zone. This is in line with research conducted by Utami (2020), which states that the greater the concentration in each formulation, the greater the inhibition of the bacteria (Maramis & Asri, 2022;Mulyani & Hendick, 2022;Mudjahid et al, 2022).…”

“…Damage to the bacterial cell wall will react with the alcohol group of the flavonoid compound, causing the absorption of these compounds into the nucleus of the bacterial cell. Then the DNA contained in the nucleus of the bacterial cell will react with the flavonoid compound through the difference in polarity between the alcohol groups and the lipids that make up the DNA, causing the nucleus of the bacterial cell to lysis (Nurhayati et al, 2020;Mudjahid et al, 2022;Utami, 2020).…”

“…Disruption of the surface tension of the cell wall causes the antibacterial content to easily enter the cell, which will eventually cause cell death. In contrast, damaged cell membranes can cause bacterial cells to experience protein and enzyme deficiencies (Fatonah et al, 2022;Sadiah et al, 2022;Mudjahid et al, 2022). The mechanism of action of tannins as an antibacterial is by inhibiting bacterial extracellular enzymes and taking over the substrates needed for bacterial growth, besides that tannins can also attack cell wall polypeptides which can eventually cause damage to the bacterial cell wall (Sukmawati et al, 2019;Adrar et al, 2019).…”

A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment

“…The results suggested that Dox MS exhibited excellent lipase response performance, which was consistent with previous reports. [ 25 ] Second, we constructed an in vitro model simulating a wound barrier to examine the penetration of microneedles and the effect on drug delivery. The results demonstrated that microneedles can effectively pierce the physical barrier of the wound and deliver the drug uniformly to the interior of the biofilms.…”

Mechanically Robust Dissolving Microneedles Made of Supramolecular Photosensitizers for Effective Photodynamic Bacterial Biofilm Elimination

“…Mechanically robust dissolving microneedle (DMN) patch can penetrate the compact EPS barrier of biofilms to deliver antibacterial agents effectively, thus showing great promise for eliminating biofilms. − Herein, for the first time, we developed a DMN patch composed of a supramolecular photosensitizer (SP) for enhanced penetration and photodynamic elimination of bacterial biofilms (Scheme ). Tetra­(4-pyridyl)-porphine (TPyP), a commonly used porphyrin derivative, was successfully included into sulfobutylether-β-cyclodextrin (SCD) through supramolecular interactions.…”