Investigating the Wound-Healing Potential of a Nanoemulsion-Gel Formulation of Pituranthos tortuosus Essential Oil.

This study explores a nanoemulsion (NE)-based gel incorporating Tunisian Pituranthos tortuosus essential oil, with a focus on its wound-healing potential. The essential oil, extracted via hydrodistillation, underwent GC-MS analysis for compositional verification. The physicochemical characterization included dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential measurement, pH, and viscosity. The gelification of the NE facilitated topical application. The results revealed an average extraction yield of 0.45% and identified 38 compounds in the essential oil. The NE exhibited a particle size of 27 ± 0.4 nm, a polydispersity index (PDI) of 0.3, and a zeta potential of -22.8 ± 1.4 mV. The stability of the gelified preparation was confirmed through thermodynamic stability studies, TEM observations, and zeta and size results. In vivo experiments confirmed significant wound-healing effects, highlighting the promising role of the NE-based gel in healthcare advancements. This research underscores the potential of novel phyto-based delivery systems in wound care.

Step-By-Step Standardization of the Bottom-Up Semi-Automated Nanocrystallization of Pharmaceuticals: A Quality By Design and Design of Experiments Joint Approach.

Nanosized drug crystals have been reported with enhanced apparent solubility, bioavailability, and therapeutic efficacy compared to microcrystal materials, which are not suitable for parenteral administration. However, nanocrystal design and development by bottom-up approaches are challenging, especially considering the non-standardized process parameters in the injection step. This work aims to present a systematic step-by-step approach through Quality-by-Design (QbD) and Design of Experiments (DoE) for synthesizing drug nanocrystals by a semi-automated nanoprecipitation method. Curcumin is used as a drug model due to its well-known poor water solubility (0.6 µg mL-1, 25 °C). Formal and informal risk assessment tools allow identifying the critical factors. A fractional factorial 24-1 screening design evaluates their impact on the average size and polydispersity of nanocrystals. The optimization of significant factors is done by a Central Composite Design. This response surface methodology supports the rational design of the nanocrystals, identifying and exploring the design space. The proposed joint approach leads to a reproducible, robust, and stable nanocrystalline preparation of 316 nm with a PdI of 0.217 in compliance with the quality profile. An orthogonal approach for particle size and polydispersity characterization allows discarding the formation of aggregates. Overall, the synergy between advanced data analysis and semi-automated standardized nanocrystallization of drugs is highlighted.

Thymoquinone-loaded self-nano-emulsifying drug delivery system against ischemia/reperfusion injury.

In the present study, a self-nano-emulsifying drug delivery system (SNEDDS) was developed to evaluate the efficiency of thymoquinone (TQ) in hepatic ischemia/reperfusion. SNEDDS was pharmaceutically characterized to evaluate droplet size, morphology, zeta potential, thermodynamic stability, and dissolution/diffusion capacity. Animals were orally pre-treated during 10 days with TQ-loaded SNEDDS. Biochemical analyses, hematoxylin-eosin staining, indirect immunofluorescence, and reverse transcription polymerase chain reaction (RT-PCR) were carried out to assess cell injury, oxidative stress, inflammation, and apoptosis. The TQ formulation showed good in vitro characteristics, including stable nanoparticle structure and size with high drug release rate. In vivo determinations revealed that TQ-loaded SNEDDS pre-treatment of rats maintained cellular integrity by decreasing transaminase (ALT and AST) release and preserving the histological characteristics of their liver. The antioxidant ability of the formulation was proven by increased SOD activity, reduced MDA concentration, and iNOS protein expression. In addition, this formulation exerted an anti-inflammatory effect evidenced by reduced plasma CRP concentration, MPO activity, and gene expressions of TLR-4, TNF-α, NF-κB, and IL-6. Finally, the TQ-loaded SNEDDS formulation promoted cell survival by enhancing the Bcl-2/Bax ratio. In conclusion, our results indicate that TQ encapsulated in SNEDDS significantly protects rat liver from I/R injury.

Development of Nanotechnology-Based Drug Delivery Systems for Controlling Clinical Multidrug-Resistant Staphylococcus aureus and Escherichia coli Associated with Aerobic Vaginitis.

The growing prevalence of resistance to antibiotics potentially makes Escherichia coli and Staphylococcus aureus serious pathogens, necessitating the development of new antimicrobial agents. We extracted crude biosurfactants from a potential probiotic Bacillus spp. to control pathogenic bacteria associated with aerobic vaginal infection. Using nanotechnology formulations, we developed nanoemulsions based on biosurfactants at different concentrations (1% and 3.33%). The results showed that these nanoemulsions were stable, with a weighted index of 0.3, and demonstrated broad-spectrum antibacterial activity against Escherichia coli and Staphylococcus aureus, with MICs ranging between 1.25 and 4 mg/mL. Additionally, the nanoemulsions exhibited interesting antibiofilm effects. All strains became more sensitive to the antibiotics to which they were resistant because of various biosurfactant formulations combined with antibiotics. Lower concentrations of BNE1% and 3.33% were still more efficient than the crude biosurfactants. Our findings demonstrated that the biosurfactant had a strong antibiofilm effect against all tested pathogens. This antibacterial effect can be explained by their ability to alter cell physiology such as cell hydrophobicity and membrane disintegration. Thus, we can conclude that the use of nanotechnology formulations has improved this effect, and the nanoemulsions developed in this study can be used as a potential anti-infectious therapy against multidrug-resistant bacterial strains of clinical origin.

Self-emulsifying Drug Delivery System for Improved Dissolution and Oral Absorption of Quetiapine Fumarate: Investigation of Drug Release Mechanism and In-vitro Intestinal Permeability.

In this study, we focused on quetiapine fumarate (QTF), a class II BCS drug. QTF is an atypical antipsychotic used in the treatment of schizophrenia and bipolar disorders. Our objective was to develop a new QTF-loaded self-emulsifying drug delivery system (SEDDS) to improve the dissolution and absorption of the drug. An experimental design approach was used to develop and optimize QTF-loaded SEDDS. The optimized formulation was characterized for droplets size, zeta potential, PDI, and stability. It was then evaluated using an in-vitro combined test for dissolution and Everted gut sac technique. Mathematical modeling and Transmission electron microscopy (TEM) were used to elucidate the mechanism of release. The optimal formulation was type IIIB SEDDS, constituted of 9.1% of oleic acid, 51.6% of Tween®20, and 39.3% of Transcutol® P. It showed a droplets size of 144.8 ± 4.9nm with an acceptable PDI and zeta potential. For in-vitro evaluation tests, we noticed an enhancement of the dissolution rate of the optimal QTF-loaded SEDDS compared to the free drug (98.82 ± 1.24% for SEDDS after 30 min compared to 85.65 ± 2.5% for the pure drug). The release of QTF fitted with the Hopfenberg model indicating the drug was released by water diffusion and erosion mechanism. This result was confirmed by TEM images which showed a smaller droplet size after release. We also found an amelioration of the permeability of QTF of 1.69-fold from SEDDS compared to the free drug. Hence, the SEDDS formulation represented a new way to improve the dissolution and absorption of QTF.

Contribution of Nanotechnologies to Vaccine Development and Drug Delivery against Respiratory Viruses.

According to the Center for Disease Control and Prevention (CDC), the coronavirus disease 2019, a respiratory viral illness linked to significant morbidity, mortality, production loss, and severe economic depression, was the third-largest cause of death in 2020. Respiratory viruses such as influenza, respiratory syncytial virus, SARS-CoV-2, and adenovirus, are among the most common causes of respiratory illness in humans, spreading as pandemics or epidemics throughout all continents. Nanotechnologies are particles in the nanometer range made from various compositions. They can be lipid-based, polymer-based, protein-based, or inorganic in nature, but they are all bioinspired and virus-like. In this review, we aimed to present a short review of the different nanoparticles currently studied, in particular those which led to publications in the field of respiratory viruses. We evaluated those which could be beneficial for respiratory disease-based viruses; those which already have contributed, such as lipid nanoparticles in the context of COVID-19; and those which will contribute in the future either as vaccines or antiviral drug delivery systems. We present a short assessment based on a critical selection of evidence indicating nanotechnology's promise in the prevention and treatment of respiratory infections.

Cationic lipid nanoparticle production by microfluidization for siRNA delivery.

Microfluidization has been investigated as a new, scalable, and basic component saving method to produce cationic lipid nanoparticles, in particular for the delivery of short interfering RNAs (siRNAs). The design of experiment (DoE) allowed to reach optimized characteristics in terms of nanocarrier size reduction and low polydispersity. The structure of cationic liposomes and siRNA-lipoplexes was characterized. The optimized preparation parameters were identified as three microfluidization passages at a pressure of 10,000 psi, with a thin film hydration volume of 4 ml. Microfluidized liposomes mean size was 160 nm, with a polydispersity index of 0.2-0.3 and a zeta potential of +40 mV to +60 mV. Positive versus negative charge ratio between the charges of the cationic lipid and the phosphate charges of the siRNAs is a key factor determining the structure and silencing efficacy of siRNA lipoplexes. At a (+/-) charge ratio of 8, a proportion of 88% of the siRNA was associated to microfluidized lipoplexes, which remained stable for one month. These lipoplexes exhibited moderate cytotoxicity and gene silencing efficacy, which should be further optimized.

Voriconazole-loaded self-nanoemulsifying drug delivery system (SNEDDS) to improve transcorneal permeability.

The aim of this study was to develop self- nanoemulsifying drug delivery system (SNEDDS) to improve the transcorneal permeability of voriconazole. A 'mixture design around a reference mixture' approach was applied. This latter included four components, namely, isopropyl myristate, PEG 400, Tween® 80 and Span® 80 as oil, co-solvent, surfactant and co-surfactant, respectively. Droplet size was selected as response. The effect of mixture components on droplet size was analyzed by means of response trace method. Optimal formulation was subjected to stability studies and characterized for droplet size, polydispersity index (PDI), pH, osmolarity, viscosity and percentage of transmittance. Ex-vivo transcorneal permeation of the optimal and the marketed formulations was carried out on excised bovine cornea using Franz cell diffusion apparatus. Optimal voriconazole loaded-SNEDDS showed moderate emulsification efficiency and was characterized by a droplet size of 21.447 ± 0.081 nm, a PDI of 0.156 ± 0.004, a pH of 7.205 ± 0.006, an osmolarity of 310 mosmol/Kg and a viscosity of 8.818 ± 0.076 cP. Moreover, it presented an excellent stability and exhibited a significant improvement (p < 0.05) in apparent permeability coefficient (1.982 ± 0.187 × 10-6 cm/s) when compared to commercialized formulation (1.165 ± 0.106 × 10-6 cm/s). These results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery.

Self-emulsifying drug delivery system developed by the HLB-RSM approach: Characterization by transmission electron microscopy and pharmacokinetic study.

Recently, we developed a new approach to rationalize an optimized design for self-emulsifying drug delivery system (SEDDS) by introducing the HLB and the response surface as determinant factors in SEDDS development. The aim of this current paper is to assess the suitability of this HLB-RSM approach to enhance the oral bioavailability of BCS class II compounds using fenofibrate as drug model. Eight SEDDS formulations (I→VIII) were pre-selected regarding their self-emulsification capacity and their effect on increasing in vitro drug release. They were firstly evaluated for their thermodynamic stability and zeta potential. Unstable SEDDS were discarded meanwhile the structural morphology of the stable ones (I, VI and VIII) was characterized using transmission electron microscopy (TEM). A pharmacokinetic study was then undertaken on male BALB/cJRj mices. The in vivo results showed a significant increase of fenofibrate absorption for all the three stable SEDDS formulations compared to the commercialized form, (LIPANTHYL micronized(®) (p<0.05)). The highest enhancement was recorded for SEDDS I, where AUC and Cmax values respectively increased by 2 and 4.4 folds. This justifies the fact that HLB-RSM approach could be considered as a promising method for the development of efficient and highly stable SEDDS aiming to increase the poor bioavailability of BCS class II molecules.

A novel approach for the development and optimization of self emulsifying drug delivery system using HLB and response surface methodology: application to fenofibrate encapsulation.

The aim of this work was to elaborate a novel approach for the development and optimization of self-emulsifying drug delivery system (SEDDS), using response surface methodology and hydrophilic lipophilic balance (HLB). Fenofibrate was selected as drug model. Rapid selection of excipients was operated with reference to their toxicity and capacity to solubilize the drug. A three level Box-Behnken design was used. The independent variables were (X1) surfactants/oil, (X2) cosurfactant/surfactant and (X3) percentage of cosolvent. The high and low levels of these factors were selected with reference to the experimental domain that covers an interval of HLB from 7.8 to 15. This interval of HLB is assumed to lead to oil in water emulsification and to contain the required HLB. The responses were (Y1) droplet size and (Y2) cumulative percentage drug released in 20 mn.Various response surface graphs were constructed to understand the effects of different factor level combinations. The optimized SEDDS with predicted drug release 83.6%, and droplet size 137 nm was prepared; the experimental values were in close agreement. The required HLB was 9.85. Optimized SEDDS showed significant increase in dissolution rate compared to conventional prepared gelatin capsules. In conclusion, this paper demonstrated the reliability, rapidity, and robustness of the approach.