State of the ART (antiretroviral therapy): Long-acting HIV-1 therapeutics.

Human immunodeficiency virus (HIV) impacts millions of individuals worldwide, and well over 2/3 of those living with HIV are accessing antiviral therapies that are successfully repressing viral replication. Most often, HIV treatments and prevention are administered in the form of daily pills as combinations of multiple drugs. An emergent and effective strategy for suppressing viral replication is the application of long-acting antiretroviral therapy (LAART), or antivirals that require less-frequent, non-daily doses. Thus far, the repertoire of LAARTs includes the widely used antiviral classes of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (INSTIs) and has recently expanded to include a capsid-targeting antiviral. Possible future additions are nucleoside reverse transcriptase inhibitors (NRTIs) and nucleoside reverse transcriptase translocation inhibitors (NRTTIs). Here, we discuss the different strategies of using long-acting compounds to treat or prevent HIV-1 infection by targeting reverse transcriptase, integrase, and capsid.

The interplay of skin architecture and cellular dynamics in wound healing: Insights and innovations in care strategies.

Wound healing involves complex interactions among skin layers: the epidermis, which epithelializes to cover wounds; the dermis, which supports granulation tissue and collagen production; and the hypodermis, which protects overall skin structure. Key factors include neutrophils, activated by platelet degranulation and cytokines, and fibroblasts, which aid in collagen production during proliferation. The healing process encompasses inflammation, proliferation, and remodeling, with angiogenesis, fibroplasia, and re-epithelialization crucial for wound closure. Angiogenesis is characterized by the creation of collateral veins, the proliferation of endothelial cells, and the recruitment of perivascular cells. Collagen is produced by fibroblasts in granulation tissue, aiding in the contraction of wounds. The immunological response is impacted by T cells and cytokines. External topical application of various formulations and dressings expedites healing and controls microbial contamination. Polymeric materials, both natural and synthetic, and advanced dressings enhance healing by providing biodegradability, biocompatibility, and infection control, thus addressing tissue regeneration challenges. Numerous dressings promote healing, including films, hydrocolloids, hydrogels, foams, alginates, and tissue-engineered substitutes. Wound dressings are treated with growth factors, particularly PDGF, and antibacterial drugs to prevent infection. The challenges of tissue regeneration and infection control are evolving along with the field of wound care.

Formulation Strategies to Overcome Amphotericin B Induced Toxicity.

Fungal infection poses a major global threat to public health because of its wide prevalence, severe mortality rate, challenges involved in diagnosis and treatment, and the emergence of drug-resistant fungal strains. Millions of people are getting affected by fungal infection, and around 3.8 million people face death per year due to fungal infection, as per the latest report. The polyene antibiotic AmB has an extensive record of use as a therapeutic moiety against systemic fungal infection and leishmaniasis since 1960. AmB has broad-spectrum fungistatic and fungicidal activity. AmB exerts its therapeutic activity at the cellular level by binding to fungal sterol and forming hydrophilic pores, releasing essential cellular components and ions into the extracellular fluid, leading to cell death. Despite using AmB as an antifungal and antileishmanial at a broad scale, its clinical use is limited due to drug-induced nephrotoxicity resulting from binding the aggregated form of the drug to mammalian sterol. To mitigate AmB-induced toxicity and to get better anti-fungal therapeutic outcomes, researchers have developed nanoformulations, self-assembled formulations, prodrugs, cholesterol- and albumin-based AmB formulations, AmB-mAb combination therapy, and AmB cochleates. These formulations have helped to reduce toxicity to a certain extent by controlling the aggregation state of AmB, providing sustained drug release, and altering the physicochemical and pharmacokinetic parameters of AmB. Although the preclinical outcome of AmB formulations is quite satisfactory, its parallel result at the clinical level is insignificant. However, the safety and efficacy of AmB therapy can be improved at the clinical stage by continuous investigation and collaboration among researchers, clinicians, and pharmaceutical companies.

Mitigation Strategies against Antibody Aggregation Induced by Oleic Acid in Liquid Formulations.

Polysorbates 20 and 80 (PS20 and PS80) are commonly used in the formulations of biologics to protect against interfacial stresses. However, these surfactants can degrade over time, releasing free fatty acids, which assemble into solid particles or liquid droplets. Here, we apply a droplet microfluidic platform to analyze the interactions between antibodies and oleic acid, the primary free fatty acid resulting from the hydrolysis of PS80. We show that antibodies adsorb within seconds to the polar oleic acid-water interface, forming a viscoelastic protein layer that leads to particle formation upon mechanical rupture. By testing two different monoclonal antibodies of pharmaceutical origin, we show that the propensity to form a rigid viscoelastic layer is protein-specific. We further demonstrate that intact PS80 is effective in preventing antibody adsorption at the oleic acid-water interface only at low antibody concentrations and low pH, where oleic acid is fully protonated. Importantly, introduction of the amino acid l-arginine prevents the formation of the interfacial layer and protein particles even at high antibody concentrations (180 mg mL-1). Overall, our findings indicate that oleic acid droplets in antibody formulations can lead to the formation of protein particles via an interface-mediated mechanism. Depending on the conditions, intact PS80 alone might not be sufficient to protect against antibody aggregation. Additional mitigation strategies include the optimization of protein physicochemical properties, pH, and the addition of arginine.

Analysis of Two Oncological Drugs Futibatinib and Capivasertib via Ion-Pairing With Eosin Y as a Spectrofluorimetric and Spectrophotometric Probe.

Using spectroscopy, two quick and sensitive analytical methods based on eosin Y ion pairing were developed and assessed in order to determine capivasertib and futibatinib with high selectivity and sensitivity. The quenching impact of futibatinib or capivasertib on the eosin Y's fluorescence at a pH 3.8 and 3.3 for futibatinib and capivasertib, respectively, in 0.1-M acetate buffer solution was observed using two spectrofluorometric techniques. These techniques are regarded as the original spectrofluorometric techniques for the assay of futibatinib and capivasertib. For futibatinib and capivasertib, the quenching effect on fluorescence was ranged from 100 to 1000 and 150 to 1500 ng mL-1, respectively. The absorbance of the generated ion-pair was measured using two different spectrophotometric methods at 550 nm in aqueous buffered solutions with pH values of 3.8 and 3.3 for futibatinib and capivasertib, respectively. In the concentration range of 1.0-10.0 and 2.0-10.0 µg mL-1, Beer's law was followed. The four approaches were applied to the analysis of dosage forms with a high percent recovery successfully, and they were assessed in compliance with ICH guidelines.

Small organism models for mode of action research on anti-ageing and nootropic herbs, foods, and formulations.

With global increase in ageing population along with increasing age-related neurodegenerative diseases (NDs), development of sustainable, safe and effective solutions for promoting healthy ageing and preventing diseases has become a priority. Traditional healthcare systems/medicines prescribe several herbs, foods and formulations to promote healthy ageing and prevent and/or treat age-related diseases. However, the scientific data elucidating their mechanism of action is very limited and deeper research using different models is warranted for timely and wider use. The clinical studies and research with higher model organisms, although useful, have several practical, technical, and financial limitations. Conversely, small organism models like Yeast, Roundworm, Fruit fly, and Zebrafish, which have genetic similarities to humans, can replicate the disease features and provide behavioural, cellular and molecular insights. The common features of ageing and NDs, like amyloid protein aggregations, oxidative stress, energy dysregulation, inflammation and neurodegeneration can be mimicked in the small organism models for Alzheimer's, Parkinson's, Huntington's diseases, and Amyotrophic Lateral Sclerosis. This review focuses on small organism model- based research unveiling interesting modes of action and synergistic effects of herbal extracts, foods, and formulations, which are indicated especially for healthy ageing and management of NDs. This will provide leads for the quick and sustainable development of scientifically evaluated solutions for clinically relevant, age-related conditions.

Effect of Fluid Paraffin on the Formulation Properties of Pressure Sensitive Adhesive Formulations Containing Diclofenac Sodium.

Understanding the relationship between the release characteristics of the active ingredient in the tape formulation and the pharmaceutical characteristics of the adhesive layer can optimize therapeutic efficacy and improve patient adherence. This study aimed to clarify the effect of liquid paraffine (LP)/styrene-isoprene-styrene (SIS) triblock copolymer ratio on pressure-sensitive adhesive (PSA) formulation properties, such as adhesive properties and drug release, with a certain amount of diclofenac sodium (DFS) and tackifier. The effects of changes in PSA composition in DFS-containing tape formulations on adhesive and drug release properties were evaluated. The viscoelasticity results showed rigid gel-like behavior at low angular frequencies regardless of the LP/SIS ratio, and deformable gel-like behavior at high angular frequencies, with a maximum plasticizing effect of LP up to an LP/SIS ratio of 3.7. The peel adhesion test results showed that peel adhesion was not affected, but indicated a decreasing trend by increasing the LP/SIS ratio in the presence of DFS. Drug release test results showed that DFS release increased up to 24 h for LP/SIS ratios of up to 3.7, but decreased when the LP/SIS ratio was 6. The results of the drug permeation tests were similar to those of the drug release tests. In conclusion, it is possible to change the drug release properties by changing the amount of LP in the tape formulation; however, no definitive correlation was found between the adhesive and drug release properties.

Encapsulation of Bacillus subtilis in Electrospun Poly(3-hydroxybutyrate) Fibers Coated with Cellulose Derivatives for Sustainable Agricultural Applications.

One of the latest trends in sustainable agriculture is the use of beneficial microorganisms to stimulate plant growth and biologically control phytopathogens. Bacillus subtilis, a Gram-positive soil bacterium, is recognized for its valuable properties in various biotechnological and agricultural applications. This study presents, for the first time, the successful encapsulation of B. subtilis within electrospun poly(3-hydroxybutyrate) (PHB) fibers, which are dip-coated with cellulose derivatives. In that way, the obtained fibrous biohybrid materials actively ensure the viability of the encapsulated biocontrol agent during storage and promote its normal growth when exposed to moisture. Aqueous solutions of the cellulose derivatives-sodium carboxymethyl cellulose and 2-hydroxyethyl cellulose, were used to dip-coat the electrospun PHB fibers. The study examined the effects of the type and molecular weight of these cellulose derivatives on film formation, mechanical properties, bacterial encapsulation, and growth. Scanning electron microscopy (SEM) was utilized to observe the morphology of the biohybrid materials and the encapsulated B. subtilis. Additionally, ATR-FTIR spectroscopy confirmed the surface chemical composition of the biohybrid materials and verified the successful coating of PHB fibers. Mechanical testing revealed that the coating enhanced the mechanical properties of the fibrous materials and depends on the molecular weight of the used cellulose derivatives. Viability tests demonstrated that the encapsulated B. subtilis exhibited normal growth from the prepared materials. These findings suggest that the developed fibrous biohybrid materials hold significant promise as biocontrol formulations for plant protection and growth promotion in sustainable agriculture.

Investigation of the Impact of Manufacturing Methods on Protein-Based Long-Acting Injectable Formulations: A Comparative Assessment for Microfluidics vs. Conventional Methods.

Background/Objectives: Microparticle-based drug delivery systems offer several advantages for protein-based drug formulations, enhancing patient compliance and therapeutic efficiency through the sustained delivery of the active pharmaceutical ingredient. Over the past few decades, the microfluidics method has emerged as a continuous manufacturing process for preparing drug-encapsulating microparticles, mainly for small molecule drugs. However, comparative assessments for the conventional batch method vs. the microfluidics method for protein-based drug formulations have been lacking. The main objective of this study was to generate immunomodulatory protein drug-loaded injectable formulations using both conventional batch and microfluidics methods. METHODS: Therefore, rhCCL22-loaded poly(lactic-co-glycolic) acid (PLGA) microparticles were prepared by conventional homogenization and microfluidics methods. RESULTS: The resulting microparticles were analyzed comparatively, focusing on critical quality attributes such as microparticle size, size distribution, morphology, drug encapsulation efficiency, release kinetics, and batch-to-batch variations in relation to the manufacturing method. Our results demonstrated that the conventional method resulted in microparticles with denser surface porosity and wider size distribution as opposed to microparticles prepared by the microfluidics method, which could contribute to a significant difference in the drug-release kinetics. Additionally, our findings indicated minimal variation within batches for the microparticles prepared by the microfluidics method. CONCLUSION: Overall, this study highlights the comparative assessment of several critical quality attributes and batch variations associated with the manufacturing methods of protein-loaded microparticles which is crucial for ensuring consistency in efficacy, regulatory compliance, and quality control in the drug formulation manufacturing process.

Lipid-Based Formulation of Baricitinib for the Topical Treatment of Psoriasis.

BACKGROUND: Baricitinib, commonly used for autoimmune diseases, is typically administered orally, which can lead to systemic adverse effects. A topical formulation could potentially offer localized therapeutic effects while minimizing these side effects. OBJECTIVES: This study focuses on developing a lipid-based topical formulation of baricitinib (BCT-OS) for treating psoriasis. METHODS: The optimized formulation was then assessed for physical, chemical, and biopharmaceutical characterization. Furthermore, the anti-inflammatory efficacy of the formulation was tested in a model of psoriasis induced by imiquimod in mice, and its tolerance was determined by the evaluation of biomechanical skin properties and an inflammation test model induced by xylol in mice. RESULTS: BCT-OS presented appropriate characteristics for skin administration in terms of pH, rheology, extensibility, and stability. The formulation also demonstrated a notable reduction in skin inflammation in the mouse model, and high tolerability without affecting the skin integrity. CONCLUSIONS: BCT-OS shows promise as an alternative treatment for psoriasis, offering localized therapeutic benefits with a potentially improved safety profile compared to systemic administration.

Key Factors for Improving Predictive Accuracy and Avoiding Overparameterization of the PBPK Absorption Model in Food Effect Studies of Weakly Basic Water-Insoluble Compounds in Immediate Release Formulations.

Background/Objectives: Physiologically based pharmacokinetic (PBPK) absorption models are instrumental for assessing drug absorption prior to clinical food effect studies, though discrepancies in predictive and actual outcomes are observed. This study focused on immediate release formulations of weakly basic water-insoluble compounds, namely rivaroxaban, ticagrelor, and PB-201, to investigate factors that could improve the predictive accuracy of PBPK models regarding food effects. Methods: Comprehensive in vitro experimental results provided the basis for the development of mechanistic absorption models, which were then combined with mechanistic disposition models to predict the systemic exposure of the model drugs in both fasted and fed states. Results: The developed PBPK models showed moderate to high predictive accuracy for food effects in Caucasian populations. For the Chinese population, the ticagrelor model's initial overestimation of fed-state absorption was addressed by updating the permeability parameters from Caco-2 cell assays to those derived from parallel artificial membrane permeability assays in FaSSIF and FeSSIF media. This refinement was also applied to the rivaroxaban and ticagrelor models, leading to a more accurate representation of absorption in Caucasians. Conclusions: This study highlights the importance of apparent permeability in enhancing the predictive accuracy of PBPK absorption models for weakly basic water-insoluble compounds. Furthermore, the precipitation of PB-201 in the two-stage transfer experiments suggests that precipitation may not be a universal phenomenon for such compounds in vivo. Consequently, the precipitation rate constant, a theoretically essential parameter, should be determined based on experimental evidence to avoid overparameterization and ensure robust predictive accuracy of PBPK models.

The Design of Novel 3D-Printed, Moulded, and Oral Viscous Budesonide Formulations for Paediatrics: A Comparative Evaluation of Their Mucoadhesive Properties.

BACKGROUND/OBJECTIVES: Paediatric eosinophilic oesophagitis (EoE) treatment is challenging due to the limited number of age-appropriate formulations. This study aims to develop and evaluate oral viscous suspensions and solid formulations of budesonide (BUD), focusing on their in vitro mucoadhesive properties, to enhance drug delivery and therapeutic outcomes in paediatric EoE. METHODS: This study encompasses the development of oral viscous suspensions and orodispersible solid formulations (moulded tablets and 3D-printed dosage forms) containing BUD. The formulations underwent quality control tests as per the European Pharmacopoeia, chemical stability assessments, and an in vitro evaluation of their mucoadhesiveness properties. RESULTS: A validated analytical method enabled accurate BUD quantification and efficient extraction, and all developed formulations demonstrated chemical stability for 30 days, meeting Ph. Eur. quality standards. Three-dimensional printing using SSE successfully produced 1 mg and 0.5 mg BUD printlets, complying with quality tests for conventional tablets. Formulations containing xanthan gum (L2-XG and P1-0.5-XG) exhibited superior mucoadhesive properties. L2-XG showed significantly higher mucoadhesion than L1-MC. Among the solid formulations, P1-0.5-XG demonstrated the highest mucoadhesive properties. CONCLUSIONS: This is the first study to develop solid oral dosage forms of BUD at a very low dose, specifically for paediatric use. The results highlight the potential of 3D printing for developing individualised orodispersible BUD formulations with improved bioadhesion for paediatric EoE treatment. The L2-XG formulation and the XG-containing printlets are the most promising formulations in terms of increasing contact time with the oesophageal mucosa, which could translate into improved therapeutic efficacy in this patient population.

Novel formulations ameliorate osteoarthritis in rats by inhibiting inflammation and oxidative stress.

The study tested new oral plant-based formulations (F) on rats with monosodium iodoacetate (MIA)-induced osteoarthritis, measuring inflammation, antioxidant levels, paw size, stride, and analyzing knee joint images. Fifty-six female Sprague Dawley rats were allocated into 8 groups: (1) Control, (2) MIA (OA induced with MIA), (3) MIA + F1 [curcuminoids+gingerols+acetyl-11-keto-ß boswellic acid (AKBA)], (4) MIA + F2 (curcuminoids+Withania glycosides+AKBA), (5) MIA + F3 (curcuminoids+total withanolides+AKBA), (6) MIA + F4 (curcuminoids, AKBA), (7) MIA + UCII (type II collagen), and (8) MIA + GCHON (Glucosamine Chondroitin). Treatments F1 to F4 reduced right joint diameter and improved stride length and paw area in OA rats. Despite improvements with treatments F1 to F4, there was no significant difference between these groups (p > .05). In OA animals, F1 to F4 treatments decreased MDA levels and increased antioxidant enzymes activities (p < .001). This was done by reducing levels of inflammatory markers and enzymes like IL-1ß, IL-6, MMP-8, TNF-α, CRP, COMP, and LOX-5, while increasing the anti-inflammatory cytokine IL-10. In conclusion, these plant-based treatments significantly reduced osteoarthritis severity, slowed disease progression by reducing inflammation, and protected joints from damage, showing a protective effect in rats with induced osteoarthritis, likely due to their anti-inflammatory and antioxidant properties.

Structure, Morphology and Surface Properties of α-Lactose Monohydrate in Relation to its Powder Properties.

The particulate properties of α-lactose monohydrate (αLMH), an excipient and carrier for pharmaceuticals, is important for the design, formulation and performance of a wide range of drug products. Here an integrated multi-scale workflow provides a detailed molecular and inter-molecular (synthonic) analysis of its crystal morphology, surface chemistry and surface energy. Predicted morphologies are validated in 3D through X-ray diffraction contrast tomography. Interestingly, from aqueous solution fastest growth is found to lie along the b-axis, i.e. the longest unit cell dimension of the αLMH crystal structure reflecting the greater opportunities for solvation on the prism compared to the capping faces leading to their slower relative growth rates. The tomahawk morphology reflects the presence of ß-lactose which asymmetrically binds to the capping surfaces creating a polar morphology. The crystal lattice energy is dominated by van der Waals interactions (between lactose molecules) with electrostatic interactions contributing the remainder. Predicted total surface energies are in good agreement with those measured at high surface coverage by inverse gas chromatography, albeit their dispersive contributions are found to be higher than those measured. The calculated surface energies of crystal habit surfaces are not found to be significantly different between different crystal surfaces, consistent with αLMH's known homogeneous binding to drug molecules when formulated. Surface energies for different morphologies reveals crystals with the elongated crystal morphologies have lower surface energies compared to those with a triangular or tomahawk morphologies, correlating well with literature data that the surface energies of the lactose carriers are inversely proportional to their aerosol dispersion performance.

Nano revolutions in ischemic stroke: A critical analysis of current options and the potential of nanomedicines in diagnosis and therapeutics.

A stroke, also known as cerebrovascular accident, is a medical emergency that occurs when the blood supply to the brain is interrupted. This disruption can happen in two main ways: through a hemorrhagic stroke, where a blood vessel in the brain bursts, or through an ischemic stroke, where a blood clot blocks an artery. Both types of stroke cause damage to brain cells, leading to a range of health complications. Globally, stroke ranks as the second leading cause of death and disability.This review provides an overview of stroke, focusing on its early detection, current treatment options, and emerging therapies. We discuss the complex mechanisms that contribute to stroke development, including the roles of cells, biomolecules, and blood vessels. Additionally, the review explores recent advances in the use of nanoparticles to enhance the efficacy of the pharmacotherapy of stroke, particularly ischemic stroke. Ongoing clinical trials in stroke management are also highlighted. Timely diagnosis and prompt intervention are critical for improving patient outcomes.We aim to increase awareness and understanding of stroke among researchers and healthcare professionals, ultimately improving patient care.

Nanocarriers for Cannabinoid Delivery: Enhancing Therapeutic Potential.

Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plant are responsible for their pharmacological and therapeutic properties. However, the complexity of cannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods are plagued by solubility and absorption problems requiring innovative solutions. After conducting a thorough review of research papers and patents, it has become evident that nanotechnology holds great promise as a solution. The comprehensive review of 36 research papers has yielded valuable insights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7 specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabis using nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies and pave the way for innovative interventions and precision medicine.

Relative Bioavailability Studies With Mitapivat: Formulation and Food Effect Assessments in Healthy Subjects.

Pyruvate kinase (PK) deficiency is a rare, hereditary, hemolytic anemia caused by mutations in the PKLR gene encoding the PK enzyme. Mitapivat (previously designated AG-348) is a first-in-class, oral, allosteric activator of PK. We report results from 5 Phase 1 trials in healthy adults to characterize and compare mitapivat pharmacokinetics across different formulations and analyze food effects on mitapivat bioavailability (Studies 1-5). Pharmacokinetic assessments were peak exposure, total exposure, time to maximum plasma concentration of mitapivat, and relative bioavailability (where appropriate). Plasma total exposure of mitapivat was similar in the fasted and fed (high-fat meal or different soft foods) states after capsule, tablet, and pediatric granule formulations. Although mitapivat administration with food reduced the rate of mitapivat absorption (delay in time to maximum plasma concentration; reduction in maximum concentration) versus dosing under fasted conditions, this was not considered clinically relevant, given the lack of effect on total mitapivat exposure. Consequently, the administration instructions for mitapivat relating to food state that "patients may take mitapivat tablets with or without food." These findings will continue to inform clinical studies and development of mitapivat in adult and pediatric patients with hemolytic anemias and may help inform healthcare professionals on mitapivat dosing/administration recommendations in clinical practice.

Preparations, Applications, Patents, and Marketed Formulations of Nanoemulsions - A Comprehensive Review.

Nanoemulsions have emerged as versatile colloidal dispersions with promising applications in various fields, including pharmaceuticals, food, and cosmetics. These nano-sized emulsions, stabilized by surfactants, offer unique advantages such as enhanced ingredient penetration efficacy and versatile dosage forms. This article provides an extensive overview of nanoemulsions, covering their composition, methods of preparation, and applications in drug delivery, the food industry, and cosmetics. Various high-energy and low-energy methods for nanoemulsion preparation are discussed, along with their advantages and limitations. Additionally, the article highlights the potential of nanoemulsions in improving drug bioavailability, stability, and therapeutic efficacy, especially in oral, topical, parenteral, intranasal, ocular, and pulmonary drug delivery. Furthermore, nanoemulsions are explored as carriers for encapsulating flavoring agents, nutraceuticals, and natural preservatives in the food industry, as well as their use in cosmetic formulations. Current clinical trials involving nanoemulsions and recent patents in the field are also summarized, providing insights into ongoing research and development efforts. Lastly, a selection of marketed nanoemulsion formulations is presented, showcasing their practical applications and commercial availability. Overall, nanoemulsions hold great promise as effective delivery systems with broad applications across various industries.

Insights into the formulation of lipid nanoparticles for the optimization of mRNA therapeutics.

mRNA-based therapeutics increasingly demonstrate significant potential in treating various diseases, including infectious diseases, cancers, and genetic disorders. Effective delivery systems are crucial for advancing mRNA therapeutics. Lipid nanoparticles (LNPs) serve as an excellent carrier, widely validated for their safety and tolerability in commercially available mRNA vaccines. Standard LNPs typically consist of four components: ionizable lipids (ILs), helper lipids, cholesterol, and polyethylene glycol-lipids (PEG-lipids), with the structural design of ILs gradually becoming a focal point of research interest. The chemical structures and formulations of the other components also significantly affect the delivery efficiency, targeting specificity, and stability of LNPs. The complex formulations of LNPs may hinder the clinical transformation of mRNA therapeutics and have raised widespread concerns about their safety. This review aims to summarize the progress of LNPs-based mRNA therapeutics in clinical trials, focusing on adverse effects that occurred during these trials. It also discusses representative innovations in LNP components, highlighting challenges and potential ways in this research field. We firmly believe this review will promote further improvements and designs of LNP compositions to optimize mRNA therapeutics. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures.

Quantitation of Usnic acid from three Usnea species, its commercial formulations Using High-Performance Thin-Layer Chromatography-Mass Spectrometry (HPTLC-MS) and their metabolite profiling using UPLC-QTof-MSE.

BACKGROUND: The genus Usnea (Parmeliaceae; lichenized Ascomycetes) is pale grayish-green fruticose lichens which grow as leafless mini-shrubs and comprise about 360 species. Most of the Usnea species are edible and is utilized in preparation of traditional foods as well as in medicines to combat wide range of ailments. OBJECTIVE: The goal of this work was to quantify usnic acid in three Usnea spp. [Usnea ghattensis (UG), Usnea orientalis (UO) and Usnea undulata (UU)] using HPTLC-MS and chemical profiling of acetone extracts using UPLC-QTof-MSE resulted in the identification of sixteen compounds based on their MS/MS fragmentation patterns. METHODS: Hyphenated techniques, HPTLC-MS and UPLC-QTof-MSE have been proposed to quantify usnic acid and analysis of metabolites in the crude extracts qualitatively. This method allowed tentative characterization of metabolites from Usnea spp. RESULTS: The quantification study showed the excellent linearity of the usnic acid at 0.25-1 µg/band with a correlation coefficient r  2>0.99, and LOD, LOQ was found to be 51.7 and 156.6 ng/band, respectively. Further, UPLC-QTof-MSE analysis of crude extract led identification of lichen substances through their exact molecular masses and MS/MS fragmentation studies. CONCLUSIONS: The present study summarizes HPTLC method for quantification of usnic acid in three different Usnea spp. Along with two herbal formulations containing Usnea spp. as the ingredient and developed method was validated as per the ICH guidelines and further UPLC-QTof-MSE analysis provides characterization of the sixteen different secondary metabolites based on their mass fragmentation studies. HIGHLIGHTS: Rapid HPTLC method for quantification of usnic acid in three different Usnea spp. along with two herbal formulations and metabolite profiling using UPLC-QTof-MSE.