Synthesis of polymeric nanoparticles by double emulsion and pH-driven: encapsulation of antibiotics and natural products for combating Escherichia coli infections.

The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against Escherichia coli underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by E. coli. KEY POINTS: • The double emulsion method provides control over size and release of bioactives. • The pH-driven method improves the solubility, stability, and release of active. • The methods increase the antibacterial action of those encapsulated in PNPs.

Olive oil nanoemulsion containing curcumin: antimicrobial agent against multidrug-resistant bacteria.

The present work aimed to develop, characterize, and evaluate the antibacterial and antibiofilm activity of two nanoemulsions (NEs) containing 500 µg/mL of curcumin from Curcuma longa (CUR). These NEs, produced with heating, contain olive oil (5%) and the surfactants tween 80 (5%) and span 80 (2.5%), water q.s. 100 mL, and were stable for 120 days. NE-2-CUR presented Ø of 165.40 ± 2.56 nm, PDI of 0.254, ζ of - 33.20 ± 1.35 mV, pH of 6.49, and Entrapment Drug Efficiency (EE) of 99%. The NE-4-CUR showed a Ø of 105.70 ± 4.13 nm, PDI of 0.459, ζ of - 32.10 ± 1.45 mV, pH of 6.40 and EE of 99.29%. Structural characterization was performed using DRX and FTIR, thermal characterization using DSC and TG, and morphological characterization using SEM, suggesting that there is no significant change in the CUR present in the NEs and that they remain stable. The MIC was performed by the broth microdilution method for nine gram-positive and gram-negative bacteria, as well as Klebsiella pneumoniae clinical isolates resistant to antibiotics and biofilm and efflux pump producers. The NEs mostly showed a bacteriostatic profile. The MIC varied between 125 and 250 µg/mL. The most sensitive bacteria were Staphylococcus aureus and Enterococcus faecalis, for which NE-2-CUR showed a MIC of 125 µg/mL. The NEs and ceftazidime (CAZ) interaction was also evaluated against the K. pneumoniae resistant clinical isolates using the Checkerboard method. NE-2-CUR and NE-4-CUR showed a synergistic or additive profile; there was a reduction in CAZ MICs between 256 times (K26-A2) and 2 times (K29-A2). Furthermore, the NEs inhibited these isolates biofilms formation. The NEs showed a MBIC ranging from 15.625 to 250 µg/mL. Thus, the NEs showed physicochemical characteristics suitable for future clinical trials, enhancing the CAZ antibacterial and antibiofilm activity, thus becoming a promising strategy for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae. KEY POINTS: • The NEs showed physicochemical characteristics suitable for future clinical trials. • The NEs showed a synergistic/additive profile, when associated with ceftazidime. • The NEs inhibited biofilm formation of clinical isolates.

Incorporation of essential oils in polymeric films for biomedical applications.

Natural and synthetic biodegradable polymers are widely used to obtain more sustainable films with biological, physicochemical, and mechanical properties for biomedical purposes. The incorporation of essential oils (EOs) in polymeric films can optimize the biological activities of these EOs, protect them from degradation, and serve as a prototype for new biotechnological products. This article aims to discuss updates over the last 10 years on incorporating EOs into natural and synthetic biodegradable polymer films for biomedical applications. Chitosan, alginates, cellulose, and proteins such as gelatine, silk, and zein are among the natural polymers most commonly used to prepare biodegradable films for release EOs. In addition to these, the most cited synthetic biodegradable polymers are poly(L-lactide) (PLA), poly(vinyl alcohol) (PVA), and poly(ε-caprolactone) (PCL). The EOs of clove, cinnamon, tea tree, eucalyptus, frankincense, lavender, thyme and oregano incorporated into polymeric films have been the most studied EOs in recent years in the biomedical field. Biomedical applications include antimicrobial activity against pathogenic bacteria and fungi, anticancer activity, potential for tissue engineering and regeneration with scaffolds and wound healing as dressings. Thus, this article reports on the importance of incorporating EOs into biodegradable polymer films, making these systems especially attractive for various biomedical applications.

Pentoxifylline/Chitosan Films on Wound Healing: In Vitro/In Vivo Evaluation.

This study aimed to develop films of chitosan (CSF) associated with pentoxifylline (PTX) for healing cutaneous wounds. These films were prepared at two concentrations, F1 (2.0 mg/mL) and F2 (4.0 mg/mL), and the interactions between the materials, structural characteristics, in vitro release, and morphometric aspects of skin wounds in vivo were evaluated. The formation of the CSF film with acetic acid modifies the polymeric structure, and the PTX demonstrates interaction with the CSF, in a semi-crystalline structure, for all concentrations. The release for all films was proportional to the concentration, with two phases: a fast one of ≤2 h and a slow one of >2 h, releasing 82.72 and 88.46% of the drug after 72 h, being governed by the Fickian diffusion mechanism. The wounds of the mice demonstrate a reduction of up to 60% in the area on day 2 for F2 when compared to CSF, F1, and positive control, and this characteristic of faster healing speed for F2 continues until the ninth day with wound reduction of 85%, 82%, and 90% for CSF, F1, and F2, respectively. Therefore, the combination of CSF and PTX is effective in their formation and incorporation, demonstrating that a higher concentration of PTX accelerates skin-wound reduction.

Bicontinuous microemulsions containing Melaleuca alternifolia essential oil as a therapeutic agent for cutaneous wound healing.

The Melaleuca alternifolia essential oil (MEO) has been widely used due to its healing and antimicrobial action. Its incorporation into drug delivery systems is a reality, and numerous studies have already been developed for this purpose. In this regard, the aim of this work was to develop, characterize, and evaluate the in vivo pharmacological activity of bicontinuous microemulsions (BME) containing MEO. Through diagram construction, a formulation consisting of Kolliphor® HS 15 (31.05%), Span® 80 (3.45%), isopropyl myristate (34.5%), and distilled water (31%) was selected and MEO was incorporated in the proportion of 3.45% (v/v). Morphological analysis characterization confirms that the system studied herein is a BME. The evaluated formulation showed physicochemical characteristics that allow its topical use. Rheologically, samples were characterized as pseudo-plastic non-Newtonian thixotropic fluids. The chromatographic method developed is in accordance with the current recommendations. The extraction method used assured a 100% recovery of the pharmacological marker (terpinen-4-ol). In vivo studies suggest that BME loaded with MEO may contribute to the healing process of skin wounds. In addition, it demonstrated antibacterial activity for Gram-positive and Gram-negative bacteria. Therefore, the BME system loaded with MEO is promising as a healing and antimicrobial agent for skin wounds.Graphical abstract.