Pharmaceutical strategies for the treatment of bacterial biofilms in chronic wounds

Biofilms are sessile communities of microorganisms, mainly bacteria, that grow on biotic and abiotic surfaces. These microorganisms are embedded within an extracellular polymeric substance that provides enhanced protection from antimicrobials. Chronic wounds provide an ideal habitat for biofilm formation. Bacteria can easily attach to wound debris and can infect the wound due to an impaired host immune response. This review highlights the mechanism of biofilm formation and the role of biofilms in the pathophysiology of chronic wounds. Our major focus is on various formulation strategies and delivery systems that are employed to eradicate or disperse biofilms, thereby effectively managing acute and chronic wounds. We also discuss clinical research that has studied or is studying the treatment of biofilm-infected chronic wounds

Levofloxacin loaded clove essential oil nanoscale emulsion as an efficient system against Pseudomonas aeruginosa biofilm

Biofilm formation by bacteria has become one of the major reasons for escalation of antimicrobial resistance. The present research focused on the development, optimization and evaluation of antibiofilm potential of clove oil nanoscale emulsion (o/w) loaded with levofloxacin (LFX-NE) against Pseudomonas aeruginosa biofilm. The optimized NE was selected through the construction of pseudo-ternary phase diagrams and was found to be stable. The particle size and drug content of LFX-NE was found to be 18.84 ± 0.5 nm and 99.2 ± 0.5%, respectively. It demonstrated high antibacterial activity with 16-fold and 8-fold reduction in MIC of LFX against P. aeruginosa and Escherichia coli and Klebsiella pneumoniae, respectively. LFX-NE was able to eradicate pre-formed biofilm of P. aeruginosa as evidenced by field emission scanning electron microscopy and confocal laser scanning microscopy. Antiquorum sensing study revealed inhibition of quorum sensing activity. LFX-NE was found to be non-irritant and cytocompatible as confirmed by HET-CAM test and safety study in normal human epidermal keratinocytes (NHEK) cell line. This study demonstrates the potential of LFX-NE in possible treatment of non-healing wounds inflicted with bacterial biofilm

Development of nanoemulgel of 5-Fluorouracil for skin melanoma using glycyrrhizin as a penetration enhancer

The purpose of this study was to enhance the topical delivery of 5-Fluorouracil (5-FU), a cancer treatment, by developing a nanoemulgel formulation. Glycyrrhizin (GLY), a natural penetration enhancer has been investigated to exhibit synergistic effects with 5-FU in inhibiting melanoma cell proliferation and inducing apoptosis, Hence, GLY, along with suitable lipids was utilized to create an optimized nanoemulsion (NE) based gel. Solubility studies and ternary phase diagram revealed isopropyl myristate (IPM), Span 80, Tween 80 as Smix and Transcutol P as co-surfactant. IPM demonstrates excellent solubilizing properties facilitates higher drug loading, ensuring efficient delivery to the target site.,The optimized formulation consisting of 40 % IPM, 30 % of mixture of Tween80: Span80 (Smix) and 15 % Transcutol P provides with a nanometric size of 64.1 ± 5.13 nm and drug loading of 97.3 ± 5.83 %. The optimized formulation observed with no creaming and breakeing of NE and found thermodynamically stable during different stress conditions (temperatures of 4.0 °C and 45.0 °C) and physical thawing (−21.0 ± 0.50 °C to 20.0 ± 0.50 °C). The NE was then transformed into a nanoemulgel (NEG) using 1.5 % w/w Carbopol base and 0.1 % w/w glycyrrhizin. The ex vivo permeability studies showed significant enhancements in drug permeability with the GLY-based 5-FU-NEG formulation compared to pure 5-FU gel in excised pig skin upto1440 min in PBS 7.4 as receptor media. The IC50 values for Plain 5-FU gel, 5-FU-NEG, and GLY-based 5-FU-NEG were found to be 20 µg/mL, 1.1 µg/mL, and 0.1 µg/mL, respectively in B16F10 cell lines. The percentage intracellular uptake of GLY-5-FU-NEG and 5-FU-NEG was found to be 44.3 % and 53.6 %, respectively. GLY-based 5-FU-NEG formulation showed alterations in cell cycle distribution, in compared to 5-FU-NE gel. The overall findings suggest that the GLY-based 5-FU-NEG holds promise for improving anti-melanoma activity

In vitro physicochemical characterization of nanocarriers: a road to optimization

Today's drug delivery scientists and pharmaceutical technologists own unprecedented variety of characterization techniques at their disposal not only to assign precise numerical values to the particle parameters but also to probe their developmental phases as well as their internal environment. Therefore, mechanistic understanding of structure-function relationships of nanotherapeutic systems seems to be a dynamic avowal considering the optimization of final nanoformulation system intended for biodistribution and targeting. This chapter aims to decipher the key in vitro physicochemical parameters in dry state, liquid state, as well as in both dry and liquid states, with the perspective of nanoparticle technology, and the diverse physical and experimental means in which these parameters can be demarcated. Further, an attempt has been made to introduce some best suited specialized techniques that enable to expand the accessible range of information to gain deeper insights into specific nanoplatform properties

In vitro physicochemical characterization of nanocarriers: a road to optimization

Today's drug delivery scientists and pharmaceutical technologists own unprecedented variety of characterization techniques at their disposal not only to assign precise numerical values to the particle parameters but also to probe their developmental phases as well as their internal environment. Therefore, mechanistic understanding of structure-function relationships of nanotherapeutic systems seems to be a dynamic avowal considering the optimization of final nanoformulation system intended for biodistribution and targeting. This chapter aims to decipher the key in vitro physicochemical parameters in dry state, liquid state, as well as in both dry and liquid states, with the perspective of nanoparticle technology, and the diverse physical and experimental means in which these parameters can be demarcated. Further, an attempt has been made to introduce some best suited specialized techniques that enable to expand the accessible range of information to gain deeper insights into specific nanoplatform properties

Engineered Site Specific Vesicular Systems for Colonic Delivery: Trends and Implications

Steering drug loaded, site-specific, coated lipid vesicles to the target receptor sites has the potential of plummeting adverse effects and improving the pharmacological response in diverse pathologies of large bowel, especially colon. Colonic delivery via oral route has its own challenges, often governed by several glitches such as drug degradation or absorption in the upper GIT, instability of proteins/peptides due to high molecular weight and peptidase activity in the stomach. Consequently, colon specific coated liposomal systems (CSLS) offer a potential alternate for not only site specificity, but protection from proteolytic activity, and prolonged residence time for greater systemic bioavailability. On the other hand, liposomal delivery via oral route is also cumbersome owing to several barriers such as instability in GIT, difficulty in crossing membranes and issues related to production at pilot scale. New advancements in the field of CSLS have successfully improved the stability and permeability of liposomes for oral delivery via modulating the compositions of lipid bilayers, adding polymers or ligands. Despite these ostensible propitiousnesses, no commercial oral CSLS has advanced from bench to bedside for targeted delivery to the colon as yet. Nevertheless, CSLS have quite fascinated the manufacturers owing to its potential industrial viability, simplistic and low-cost design. Hence, this review aims to decipher the convolutions involved in the engineering process of industrially viable CSLS for colonic delivery