Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin.

Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of -45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival after UVA-irradiation, reduced lipid peroxidation, and increased the antioxidant enzymes' activities in human dermal fibroblasts (Fbs) compared to free EGCG. Finally, the uptake of niosomes was via energy-dependent endocytosis. The optimised niosomes have the potential to be used as a dermal carrier for antioxidants and other therapeutic compounds in the pharmaceutical and cosmetic industries.

Nanomaterials: The New Antimicrobial Magic Bullet.

Bacterial infections are a significant cause of mortality and morbidity worldwide, despite decades of use of numerous existing antibiotics and constant efforts by researchers to discover new antibiotics. The emergence of infections associated with antibiotic-resistant bacterial strains, has amplified the pressure to develop additional bactericidal therapies or new unorthodox approaches that can deal with antimicrobial resistance. Nanomaterial-based strategies, particularly those that do not rely on conventional small-molecule antibiotics, offer promise in part due to their ability to dodge existing mechanisms used by drug-resistant bacteria. Therefore, the use of nanomaterial-based formulations has attracted attention in the field of antibiotic therapy. In this Review, we highlight novel and emerging nanomaterial-based formulations along with details about the mechanisms by which nanoparticles can target bacterial infections and antimicrobial resistance. A detailed discussion about types and the activities of nanoparticles is presented, along with how they can be used as either delivery systems or as inherent antimicrobials, or a combination of both. Lastly, we highlight some toxicological concerns for the use of nanoparticles in antibiotic therapies.

Understanding the relationship between solubility and permeability of γ-cyclodextrin-based systems embedded with poorly aqueous soluble benznidazole.

When administered orally, the bioavailability of drugs is strongly influenced by their aqueous solubility and permeability. Although solubility-enabling excipients can improve the aqueous solubility of lipophilic drugs, their simultaneous effect on the apparent permeability can be often overlooked. Recently, we demonstrated that the aqueous dissolution of poorly aqueous soluble benznidazole (BNZ) was improved by γ-CD complexation, but the potential impact of γ-CD complexation on the permeability of BNZ remained unexplored. Therefore, the aim of this work was to study the relationship between the aqueous solubility and apparent permeability of BNZ:γ-CD-based formulations, employing both non-cell-based parallel artificial membrane permeability assay (PAMPA) and cell-based (Caco-2 and mucus-producing Caco-2/HT29-MTX co-culture cell model) permeability models. The increase in BNZ aqueous solubility was directly proportional to the γ-CD concentration (from 185 µg mL-1 up to 320 µg mL-1 when 20 mM γ-CD was used in the formulation) and resulted in an increased apparent permeability, though in some cases a decrease was observed. Specifically, in the Caco-2/HT29-MTX cell model an increase in aqueous solubility did not always result in the increase of apparent permeability, with higher γ-CD concentrations leading to a decrease in apparent permeability Papp values down to 3.248 × 10-5 cm s-1 at γ-CD concentration of 30 mM (from 5.164 × 10-5 cm s-1 for 15 mM γ-CD) despite a continuing increase in solubility. Overall, the solubility enhancement of BNZ by γ-CD complexation had different effects on its permeability depending on the permeability model employed, and these effects should be taken into consideration when using solubility-enabling excipients.

Engineering mesoporous silica nanoparticles towards oral delivery of vancomycin.

Vancomycin (Van) is a key antibiotic of choice for the treatment of systemic methicillin resistant Staphylococcus aureus (MRSA) infections. However, due to its poor membrane permeability, it is administered parenterally, adding to the cost and effort of treatment. The poor oral bioavailability of Van is mainly due to its physico-chemical properties that limit its paracellular and transcellular transport across gastrointestinal (GI) epithelium. Herein we report the development of silica nanoparticles (SNPs)-based formulations that are able to enhance the epithelial permeability of Van. We synthesized SNPs of different pore sizes (2 nm and 9 nm) and modified their surface charge and polarity by attaching different functional groups (-NH2, -PO3, and -CH3). Van was loaded within these SNPs at a loading capacity in the range of ca. 18-29 wt%. The Van-loaded SNPs exhibited a controlled release behaviour when compared to un-encapsulated Van which showed rapid release due to its hydrophilic nature. Among Van-loaded SNPs, SNPs with large pores showed a prolonged release compared to SNPs with small pores while SNPs functionalised with -CH3 groups exhibited a slowest release among the functionalised SNPs. Importantly, Van-loaded SNPs, especially the large pore SNPs with negative charge, enhanced the permeability of Van across an epithelial cell monolayer (Caco-2 cell model) by up to 6-fold, with Papp values up to 1.716 × 10-5 cm s-1 (vs. 0.304 × 10-5 cm s-1 for un-encapsulated Van) after 3 h. The enhancement was dependent on both the type of SNPs and their surface functionalisation. The permeation enhancing effect of SNPs was due to its ability to transiently open the tight junctions measured by decrease in transepithelial resistance (TEER) which was reversible after 3 h. All in all, our data highlights the potential of SNPs (especially SNPs with large pores) for oral delivery of Van or other antimicrobial peptides.

Formulation technologies and advances for oral delivery of novel nitroimidazoles and antimicrobial peptides.

Antibiotic resistance has become a global crisis, driving the exploration for novel antibiotics and novel treatment approaches. Among these research efforts two classes of antibiotics, bicyclic nitroimidazoles and antimicrobial peptides, have recently shown promise as novel antimicrobial agents with the possibility to treat multi-drug resistant infections. However, they suffer from the issue of poor oral bioavailability due to disparate factors: low solubility in the case of nitroimidazoles (BCS class II drugs), and low permeability in the case of peptides (BCS class III drugs). Moreover, antimicrobial peptides present another challenge as they are susceptible to chemical and enzymatic degradation, which can present an additional pharmacokinetic hurdle for their oral bioavailability. Formulation technologies offer a potential means for improving the oral bioavailability of poorly permeable and poorly soluble drugs, but there are still drawbacks and limitations associated with this approach. This review discusses in depth the challenges associated with oral delivery of nitroimidazoles and antimicrobial peptides and the formulation technologies that have been used to overcome these problems, including an assessment of the drawbacks and limitations associated with the technologies that have been applied. Furthermore, the potential for supercritical fluid technology to overcome the shortcomings associated with conventional drug formulation methods is reviewed.

Nuts, cereals, seeds and legumes proteins derived emulsifiers as a source of plant protein beverages: A review.

Milk beverages derived from plant-based protein have attracted the interest of consumers and researchers as a health-promoting functional food. It can also be considered as a substitute for animal milk due to various allergy concerns associated with dairy milk. The plant-based emulsions are directed to prevent diet-related chronic diseases including diabetes, cardiovascular, obesity and other disorders due to the presence of healthy long-chain unsaturated fatty acids as compared to bovine milk. Further, associations between nutritional contents (vitamins, minerals and low fat) and pharmacological properties of plant-based protein may have extra beneficial effects. The review aims to summarize the four different groups of plant sources (nuts, cereals, seeds and legumes) used for the preparation of plant-based milk beverages. In addition, it also provides a detailed review of the general characteristics and functional properties of these plant sources. Physicochemical composition, protein and fats quality, functional properties, effect of heat and high-pressure treatment is also provided in detail. It also covers fats digestibility, protein stability, protein solubility and digestibility. Furthermore, the effect of processing, possible comparative study and potential applications in healthcare have been discussed.

Factorial design-assisted supercritical carbon-dioxide extraction of cytotoxic active principles from Carica papaya leaf juice.

The aims of this study are to investigate the selective cytotoxic activity of supercritical carbon dioxide (scCO2)-extracted freeze-dried leaf juice (FDLJ) of Carica papaya on squamous cell carcinoma (SCC25) cells, and to delineate the best small scale extraction parameters allowing maximal extract activity. Using scCO2 as a solvent, six operating parameters were studied and the supercritical fluid extraction (SFE) process investigated using a factorial design 26-2. The processing values promoting cytotoxic activity towards SCC-25 are: high pressure (250 bar), low temperature (35 °C), extended processing time (180 minutes), as well as a large amount of starting material (5 g). The factorial experimental design successfully identified the key parameters controlling the SFE of molecules cytotoxic to SCC cells from C. papaya juice. This study also validated the extraction method and showed that the SFE yield was reproducible. The chromatographic and mass spectrometric profiles of the scCO2 extract acquired with high-resolution quadrupole time-of-flight mass spectrometry (LC-QToF-MS) were used to tentatively identify the bioactive compounds using comparative analysis. The principal compounds were likely to be mainly vitamins and phytosterols, some of which are documented to be cytotoxic to cancer cells.

Solid nanoparticles for oral antimicrobial drug delivery: a review.

Most microbial infectious diseases can be treated successfully with the remarkable array of antimicrobials current available; however, antimicrobial resistance, adverse effects, and the high cost of antimicrobials are crucial health challenges worldwide. One of the common efforts in addressing this issue lies in improving the existing antibacterial delivery systems. Solid nanoparticles (SNPs) have been widely used as promising strategies to overcome these challenges. In addition, oral delivery is the most common method of drug administration with high levels of patient acceptance. Formulation into NPs can improve drug stability in the harsh gastrointestinal (GI) tract environment, providing opportunities for targeting specific sites in the GI tract, increasing drug solubility and bioavailability, and providing sustained release in the GI tract. Here, we discuss SNPs for the oral delivery of antimicrobials, including solid lipid NPs (SLNs), polymeric NPs (PNs), mesoporous silica NPs (MSNs) and hybrid NPs (HNs). We also discussed about the role of nanotechnology in IV to oral antimicrobial therapy development as well as challenges, clinical transformation, and limitations of SNPs for oral antimicrobial drug delivery.

Solvent Supercritical Fluid Technologies to Extract Bioactive Compounds from Natural Sources: A Review.

Supercritical fluid technologies offer a propitious method for drug discovery from natural sources. Such methods require relatively short processing times, produce extracts with little or no organic co-solvent, and are able to extract bioactive molecules whilst minimising degradation. Supercritical fluid extraction (SFE) provides a range of benefits, as well as offering routes to overcome some of the limitations that exist with the conventional methods of extraction. Unfortunately, SFE-based methods are not without their own shortcomings; two major ones being: (1) the high establishment cost; and (2) the selective solvent nature of CO2, i.e., that CO2 only dissolves small non-polar molecules, although this can be viewed as a positive outcome provided bioactive molecules are extracted during solvent-based SFE. This review provides an update of SFE methods for natural products and outlines the main operating parameters for extract recovery. Selected processing considerations are presented regarding supercritical fluids and the development and application of ultrasonic-assisted SFE methods, as well as providing some of the key aspects of SFE scalability.