Transferosomes as a transdermal drug delivery system: Dermal kinetics and recent developments.

The development of innovative approaches to deliver medications has been growing now for the last few decades and generates a growing interest in the dermatopharmaceutical field. Transdermal drug delivery in particular, remains an attractive alternative route for many therapeutics. However, due to the limitations posed by the barrier properties of the stratum corneum, the delivery of many pharmaceutical dosage forms remains a challenge. Most successful therapies using the transdermal route have been ones containing smaller lipophilic molecules with molecular weights of a few hundred Daltons. To overcome these limitations of size and lipophilicity of the drugs, transferosomes have emerged as a successful tool for transdermal delivery of a variety of therapeutics including hydrophilic actives, larger molecules, peptides, proteins, and nucleic acids. Transferosomes exhibit a flexible structure and higher surface hydrophilicity which both play a critical role in the transport of drugs and other solutes using hydration gradients as a driving force to deliver the molecules into and across the skin. This results in enhanced overall permeation as well as controlled release of the drug in the skin layers. Additionally, the physical-chemical properties of the transferosomes provide increased stability by preventing degradation of the actives by oxidation, light, and temperature. Here, we present the history of transferosomes from solid lipid nanoparticles and liposomes, their physical-chemical properties, dermal kinetics, and their recent advances as marketed dosage forms. This article is categorized under: Biology-Inspired Nanomaterials > Lipid-Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Isothiocyanate-rich moringa seed extract reduces skin inflammation in mouse ear edema model.

Background: Moringa (Moringa oleifera Lam.) seed extract (MSE) and its primary bioactive compound, moringa isothiocyanate-1(MIC-1), mitigate inflammation, oxidative stress, diabetes, and cancer in the in vivo rodent models following oral application. Purpose: To investigate the topical anti-inflammatory activity of MSE and purified MIC-1 in a TPA-induced mouse ear edema model. Study Design: The present study elucidates the topical anti-inflammatory effects and mechanisms of action of MSE, containing 38% of MIC-1 and purified MIC-1 using a mouse ear edema model utilizing 12-O-tetradecanoylphorbol-13-acetate (TPA), as the pro-inflammatory agent. Methods: A time-dependent and dose-dependent response was determined by pretreating CD-1 mice with various doses of MSE and MIC-1, positive control, dexamethasone, or vehicle control, followed by TPA, and the subsequent difference in ear thickness was measured using digital Vernier calipers. The effective doses of MSE and MIC-1were then selected to evaluate the change in weight of the ears using 6 mm biopsy punches and the results were confirmed by microscopy. Inflammatory markers were quantified with Luminex multiplex immunoassay. Results: MSE and MIC-1 were effective in a dose-dependent manner in a TPA-induced ear edema model, causing a reduction in ear thickness and a 48% and 49% decrease in ear punch weight, respectively. MSE and MIC-1 also caused a reduction in the levels of cytokine and chemokines, interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and keratinocyte chemoattractant (KC) in the ear tissue. MSE and MIC-1 reduced IL-6 expression by 84% and 78%, MCP1 by 74% and 73%, and KC by 56% and 43%, respectively. Additionally, the anti-inflammatory effect of MSE and MIC-1 was confirmed by hematoxylin and eosin (H&E) staining, used to assess the thickness of the ear swelling. MSE significantly reduced the thickness of the ears by 20% compared to TPA. Conclusion: These results reveal the topical anti-inflammatory properties of MSE, and MIC-1 likely transmitted via the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) pathways as mentioned in previous studies. This work also suggests therapeutic uses of MSE and/or MIC-1 for skin inflammation.

Chitosan-Based Hydrogels for Controlled Delivery of Asiaticoside-Rich Centella asiatica Extracts with Wound Healing Potential.

Centella asiatica extract is a valued plant material with known anti-inflammatory and anti-microbiological properties. Using the Design of Experiment (DoE) approach, it was possible to obtain an optimized water/alcoholic extract from Centella asiatica, which allowed the preparation of the final material with biological activity in the wound healing process. Studies on the novel applications of Centella asiatica in conjunction with the multifunctional chitosan carrier have been motivated by the plant's substantial pharmacological activity and the need to develop new and effective methods for the treatment of chronic wounds. The controlled release of asiaticoside was made possible by the use of chitosan as a carrier. Based on the findings of investigations using the PAMPA skin assay, which is a model imitating the permeability of actives through skin, this compound, characterized by sustained release from the chitosan delivery system, was identified as being well able to permeate biological membranes such as skin. Chitosan and the lyophilized extract of Centella asiatica worked synergistically to block hyaluronidase, exert efficient microbiological activity and take part in the wound healing process, as proven in an in vitro model. A formulation containing 3% extract with 3% medium-molecular-weight chitosan was indicated as a potentially new treatment with high compliance and effectiveness for patients. Optimization of the chitosan-based hydrogel preparation ensured the required rheological properties necessary for the release of the bioactive from the chitosan delivery system and demonstrated a satisfactory antimicrobial activity.

A Comparative Evaluation of Desoximetasone Cream and Ointment Formulations Using Experiments and In Silico Modeling.

The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery methods, such as tablets and injections. In the context of drug development, it is crucial to identify the optimal doses and delivery routes that ensure successful outcomes. Physiologically based pharmacokinetic (PBPK) models have been proposed to simulate drug delivery and optimize drug formulations, but the calibration of these models is challenging due to the multitude of variables involved and limited experimental data. One significant research gap that this article addresses is the need for more efficient and accurate methods for calibrating PBPK models for dermal drug delivery. This manuscript presents a novel approach and an integrated dermal drug delivery model to address this gap that leverages virtual in vitro release (IVRT) and permeation (IVPT) testing data to optimize mechanistic models. The proposed approach was demonstrated through a study involving Desoximetasone cream and ointment formulations, where the release kinetics and permeation profiles of Desoximetasone were determined experimentally, and a computational model was created to simulate the results. The experimental studies showed that, even though the cumulative permeation of Desoximetasone at the end of the permeation study was comparable, there was a significant difference seen in the lag time in the permeation of Desoximetasone between the cream and ointment. Additionally, there was a significant difference seen in the amount of Desoximetasone permeated through human cadaver skin at early time points when the cream and ointment were compared. The computational model was optimized and validated, suggesting that this approach has the potential to bridge the existing research gap by improving the accuracy and efficiency of drug development processes. The model results show a good fit between the experimental data and model predictions. During the model optimization process, it became evident that there was variability in both the permeability and the partition coefficient within the stratum corneum. This variability had a significant and noteworthy influence on the overall performance of the model, especially when it came to its capacity to differentiate between cream and ointment formulations. Leveraging virtual models significantly aids the comprehension of drug release and permeation, mitigating the demanding data requirements. The use of virtual IVRT and IVPT data can accelerate the calibration of PBPK models, streamline the selection of the appropriate doses, and optimize drug delivery. Moreover, this novel approach could potentially reduce the time and resources involved in drug development, thus making it more cost-effective and efficient.

Clinical Efficacy of Topical Vitamin C on the Appearance of Wrinkles: A Systematic Literature Review.

PURPOSE: A rise in market demand for anti-aging skin care products has resulted in a proliferation of cosmeceuticals, including products that contain vitamin C. Many topicals containing vitamin C claim to reduce the appearance of wrinkles. However, these claims have not been systematically evaluated. METHODS: A systematic review of literature published between January 2015 and September 2022 was performed per PRISMA guidelines. Scopus, Web of Science, and PubMed were queried for records relevant using the following Medical Subject Heading (MeSH) terms: “Topical Vitamin C OR Ascorbic acid”, “Vitamin C efficacy”, “dermatology”, “cosmetology”, and “skin anti-aging”. Variables of interest included: study type, study location, study duration, sample size, patient description, type and ingredients of the topical formulation, outcome measurement, results, and adverse events. RESULTS: After deduplication, consideration of inclusion and exclusion criteria, and title/abstract screening, 5,428 initial records were reduced to 7 articles, including 4 meeting Level IB criteria, one meeting Level IIA criteria, and 2 meeting Level IIB criteria. Methods for assessing clinical improvements included global photodamage score, skin topography assessment, reflectance confocal microscopy (RCM) skin analysis, Dynamical Atlas, and participant self-assessment.  Conclusions: While 4 of the 7 studies met Level IB evidence, further high-quality, prospective, and comparative studies are indicated to better elucidate the role of topical vitamin C in wrinkle reduction. All the studies used vitamin C in combination with other ingredients or therapeutic mechanisms, thereby complicating any specific conclusions regarding the efficacy of vitamin C. Citation: Sanabria B, Berger LE, Mohd H, et al. Clinical efficacy of topical vitamin C on the appearance of wrinkles: a systematic literature review. J Drugs Dermatol. 2023;22(9):898-904. doi:10.36849/JDD.7332.

The Antioxidant Potential of Resveratrol from Red Vine Leaves Delivered in an Electrospun Nanofiber System.

Despite the wide pharmacological action of polyphenols, their usefulness is limited due to their low oral bioavailability, which is due to their low solubility and rapid first-pass metabolism. Red vine leaf extract is an herbal medicine containing several polyphenols, with resveratrol and polydatin as the main compounds exhibiting antioxidant and anti-inflammatory properties. In the first stage of the work, using the Design of Experiment (DoE) approach, the red vine leaf extract (50% methanol, temperature 70 °C, and three cycles per 60 min) was obtained, which showed optimal antioxidant and anti-inflammatory properties. In order to circumvent the above-described limitations and use innovative technology, electrospun nanofibers containing the red vine leaf extract, polyvinylpyrrolidone (PVP), and hydroxypropyl-ß-cyclodextrin (HPßCD) were first developed. The optimization of the process involved the time of system mixing prior to electrospinning, the mixture flow rate, and the rotation speed of the collector. Dissolution studies of nanofibers showed improved resveratrol release from the nanofibers (over five-fold). Additionally, a PAMPA-GIT assay confirmed significantly better buccal penetration of resveratrol from this nanofiber combination (over ten-fold). The proposed strategy for electrospun nanofibers with the red vine leaf extract is an innovative approach to better use the synergy of the biological action of active compounds present in extracts that are beneficial for the development of nutraceuticals.

A Study of Microemulsion Systems for Transdermal Delivery of Risperidone Using Penetration Enhancers.

The aim of this study was to develop and characterize microemulsion formulations using penetration enhancers as potential transdermal delivery systems for risperidone. Initially, a simple formulation of risperidone in Propylene Glycol (PG) was prepared as a control formulation, together with formulations incorporating various penetration enhancers, alone and/or in combination, and also microemulsion formulations with various chemical penetration enhancers, were prepared and all were evaluated for risperidone transdermal delivery. An ex-vivo permeation study was carried out using human cadaver skin and vertical glass Franz diffusion cells to compare all the microemulsion formulations. The microemulsion prepared from oleic acid as the oil (15%), Tween 80 (15%) as the surfactant and isopropyl alcohol (20%) as the co-surfactant, and water (50%) showed higher permeation with a flux value of 32.50±3.60 ug/hr/sq.cm, a globule size of 2.96±0.01 nm, a polydispersity index of 0.33±0.02 and pH of 4.95. This novel in vitro research disclosed that an optimized microemulsion formulated using penetration enhancers was able to increase permeation of risperidone by 14-fold compared to the control formulation. The data suggested that microemulsions may be useful in the delivery of risperidone via the transdermal route.

The Contest of Nanoparticles: Searching for the Most Effective Topical Delivery of Corticosteroids.

Owing to their complicated pathophysiology, the treatment of skin diseases necessitates a complex approach. Conventional treatment using topical corticosteroids often results in low effectiveness and the incidence of local or even systemic side effects. Nanoformulation of potent anti-inflammatory drugs has been selected as an optimal strategy for enhanced topical delivery of corticosteroids. In order to assess the efficiency of various nanoformulations, we formulated hydrocortisone (HC) and hydrocortisone-17-butyrate (HCB) into three different systems: lipid nanocapsules (LNC), polymeric nanoparticles (PNP), and ethosomes (ETZ). The systems were characterized using dynamic light scattering for their particle size and uniformity and the morphology of nanoparticles was observed by transmission electron microscopy. The nanosystems were tested using ex vivo full thickness porcine and human skin for the delivery of HC and HCB. The skin penetration was observed by confocal microscopy of fluorescently labelled nanosystems. ETZ were proposed as the most effective delivery system for both transdermal and dermal drug targeting but were also found to have a profound effect on the skin barrier with limited restoration. LNC and PNP were found to have significant effects in the dermal delivery of the actives with only minimal transdermal penetration, especially in case of HCB administration.

Effect of Penetration Enhancers on Transdermal Delivery of Oxcarbazepine, an Antiepileptic Drug Using Microemulsions.

Oxcarbazepine (OXC) is an anticonvulsant drug, indicated for the treatment of the neurological disorder, epilepsy. The objective of the present study was to evaluate the transdermal delivery of OXC from microemulsions using different penetration enhancers. Transcutol® P (TRC), oleic acid (OA), cineole (cin), Labrasol (LS), Tween 80 (T80) and N-Methyl-Pyrrolidone (NMP) were used as penetration enhancers as well as microemulsion components. Simple formulations of OXC in propylene glycol (PG) incorporating various penetration enhancers and combination of penetration enhancers were also evaluated for transdermal delivery. Drug delivery and penetration enhancement were studied using human cadaver skin on Franz diffusion cells. The results showed that all penetration enhancers improved the rate of permeation of OXC compared to the control. The flux of drug delivery from the various formulations was found to be, in decreasing order, cin > OA + TRC > NMP > TRC > OA. Overall, microemulsions prepared using cineole, Tween 80 and Transcutol® P (TRC) were shown to be provide the best penetration enhancement for OXC.

Quality by Design Guided Development of Polymeric Nanospheres of Terbinafine Hydrochloride for Topical Treatment of Onychomycosis Using a Nano-Gel Formulation.

Superficial fungal diseases of the skin and nails are an increasingly common occurrence globally, requiring effective topical treatment to avoid systemic adverse effects. Polymeric nanoparticles have demonstrated sustained and effective drug delivery in a variety of topical formulations. The aim of this project was to develop polymeric antifungal nanospheres containing terbinafine hydrochloride (TBH) to be loaded into a hydrogel formulation for topical nail drug delivery. A quality by design (QbD) approach was used to achieve optimized particles with the desired quality target product profile (QTPP). Polyvinyl alcohol (PVA) at 2% w/v and a drug to polymer ratio of 1:4, together with a robust set of processes and material attributes, resulted in nanoparticles of 108.7 nm with a polydispersity index (PDI) of 0.63, 57.43% recovery, and other desirable characteristics such as zeta potential (ZP), particle shape, aggregation, etc. The nanospheres were incorporated into a carbomer-based gel, and the delivery of TBH through this formulation was evaluated by means of in vitro drug release testing (IVRT) and ex vivo nail permeation study. The gel containing the TBH nanospheres demonstrated a slower and controlled drug release profile compared with the control gel, in addition to a more efficient delivery into the nail. These antifungal nanospheres can be utilized for topical therapy of a multitude of superficial fungal infections.

Antifungal Nail Lacquer for Enhanced Transungual Delivery of Econazole Nitrate.

The fungal disease of the nail, onychomycosis, which is also the most prevalent nail disturbance, demands effective topical treatment options considering the possible adverse effects of systemic antifungal therapy. The current work is focused on development of an adhesive and resistant, drug-delivering and permeation-enhancing polymeric film containing econazole nitrate (ECN) for topical antifungal treatment. The development of the lacquer formulation was guided by the Quality by Design approach to achieve the critical quality attributes needed to obtain the product of desired quality. Eudragit RSPO at 10% w/w was found to be the ideal adhesive polymer for the application and an optimal permeation-enhancing lacquer formulation was achieved by the optimization of other formulation excipients, such as plasticizer and the solvent system. Additionally, novel experimental enhancements introduced to the research included refined D50 drying time and drying rate tests for lacquer characterization as well as a multi-mechanism permeation-enhancing pre-treatment. Moreover, a practical implication was provided by a handwashing simulation designed to test the performance of the lacquer during actual use. In vitro drug release testing and ex vivo nail permeation testing demonstrated that the optimized nail lacquer performed better than control lacquer lacking the permeation enhancer by achieving a faster and sustained delivery of ECN. It can be concluded that this is a promising drug delivery system for topical antifungal treatment of onychomycotic nails, and the novel characterization techniques may be adapted for similar formulations in the future.

Expert Systems for Predicting the Bioavailability of Sun Filters in Cosmetic Products, Software vs. Expert Formulator: The Benzophenone-3 Case.

There are only a limited number of molecules in a cosmetic formulation, which can passively cross the stratum corneum and be absorbed into the skin layers. However, some actives should never cross the skin in large concentrations due to their potential for side effects, for example, sunscreens. Artificial intelligence is gaining an increasing role as a predictive tool, and in this regard, we selected the Formulating for Efficacy® Software to forecast the changes in bioavailability of selected topical cosmetic compounds. Using the Franz diffusion cell methodology, various oils were selected as those with low release capability, and these were compared to those suggested by the software in Benzophenone-3-containing formulations. The software was able to predict the lipophilic phases, which, if utilized in the emulsion, were stable and sometimes even more pleasant in appearance and consistency than the reference emulsions prepared by the formulator. To date, however, Formulating for Efficacy® Software still has limitations as far as predicting the hydrophilic phase, as well as not being able to choose the emulsifier or the preservative system.

Pediatric Tuberculosis Management: A Global Challenge or Breakthrough?

Managing pediatric tuberculosis (TB) remains a public health problem requiring urgent and long-lasting solutions as TB is one of the top ten causes of ill health and death in children as well as adolescents universally. Minors are particularly susceptible to this severe illness that can be fatal post-infection or even serve as reservoirs for future disease outbreaks. However, pediatric TB is the least prioritized in most health programs and optimal infection/disease control has been quite neglected for this specialized patient category, as most scientific and clinical research efforts focus on developing novel management strategies for adults. Moreover, the ongoing coronavirus pandemic has meaningfully hindered the gains and progress achieved with TB prophylaxis, therapy, diagnosis, and global eradication goals for all affected persons of varying age bands. Thus, the opening of novel research activities and opportunities that can provide more insight and create new knowledge specifically geared towards managing TB disease in this specialized group will significantly improve their well-being and longevity.

In vitro release, ex vivo penetration, and in vivo dermatokinetics of ketoconazole-loaded solid lipid nanoparticles for topical delivery.

The study focused to evaluate and investigate optimized (using QbD) and novel ketoconazole (KTZ)-loaded solid lipid nanoparticles (KTZ-SLNs; 2% w/v KTZ) for enhanced permeation across skin. KTZ-SLNs were evaluated for size, distribution, zeta potential (ZP), percent entrapment efficiency (%EE), drug release, morphology (HRTEM and FESEM), thermal behaviour (DSC), spectroscopic (FTIR), and solid-state/diffraction characterization (X-ray diffraction, XRD). Moreover, ex vivo permeation and drug deposition into rat skin were conducted using Franz diffusion cell. The same was confirmed using human dermatome skin and fluorescence, confocal Raman, and vibrational ATR-FTIR microscopic methods. An in vivo dermatokinetics study was performed in rats to assess the extent of KTZ permeation into the skin. Stability including accelerated and photostability studies were conducted at different temperatures (2-8, 30, and 40 °C) for 12 months. The spherical, optimized KTZ-SLN formulation (KOF1) showed particle size of 293 nm and high EE of 88.5%. Results of FTIR, DSC, and XRD confirmed formation of KTZ-SLNs and their amorphous nature due to presence of KTZ in a dissolved state in the lipid matrix. In vitro release was slow and sustained whereas ex vivo permeation parameters were significantly high in KTZ-SLNs as compared to free drug suspension (KTZ-SUS) and marketed product (Nizral®; 2% KTZ w/v). Drug retention was 10- and five-fold higher than KTZ-SUS and marketed product, respectively. In vivo dermatokinetics parameters improved significantly with SLN formulation (410-900% enhanced). Confocal Raman spectroscopy experiment showed that KTZ-SLNs could penetrate beyond the human stratum corneum into viable epidermis. Fluorescent microscopy also indicated improved penetration of KTZ-SLNs. KTZ-SLNs were photostable and showed long-term stability over 12 months under set conditions.

Anti-Melanogenic Mechanism of Tetrahydrocurcumin and Enhancing Its Topical Delivery Efficacy Using a Lecithin-Based Nanoemulsion.

Tetrahydrocurcumin (THC) has been well known for its superior antioxidant properties. Therefore, it is speculated that it might be effective to relieve oxidative stress-induced diseases, such as skin hyperpigmentation. In this work, an in vitro B16F10 melanoma cell model was used to study the impact of THC on the melanogenic process under stressed conditions. It was demonstrated that THC could effectively inhibit the α-MSH (melanocyte-stimulating hormone) induced melanin production in B16F10 melanoma cells and the expressions of three key enzymes involved with the biosynthetic process of melanin, tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2), were all significantly reduced. In addition, an in vitro human keratinocyte cell model was used to investigate the potential protective role of THC on H2O2-induced cytotoxicity. It was found that THC could prevent H2O2-induced oxidative stress based on the results of both the cell viability study and the intracellular ROS (reactive oxygen species) study assessed by the flow cytometry. Last, THC was formulated into a lecithin based nanoemulsion, and an in vitro Franz diffusion cell study using Strat-M® membrane concluded that the nanoemulsion could significantly enhance the membrane permeation compared to the unformatted THC suspension. This research demonstrated the anti-melanogenic benefits of THC on the melanoma and keratinocyte cell models and the topical delivery efficacy could be significantly enhanced using a lecithin based nanoemulsion.

Recent Advances in Polymer-Based Vaginal Drug Delivery Systems.

The vagina has been considered a potential drug administration route for centuries. Most of the currently marketed and investigated vaginal formulations are composed with the use of natural or synthetic polymers having different functions in the product. The vaginal route is usually investigated as an administration site for topically acting active ingredients; however, the anatomical and physiological features of the vagina make it suitable also for drug systemic absorption. In this review, the most important natural and synthetic polymers used in vaginal products are summarized and described, with special attention paid to the properties important in terms of vaginal application. Moreover, the current knowledge on the commonly applied and innovative dosage forms designed for vaginal administration was presented. The aim of this work was to highlight the most recent research directions and indicate challenges related to vaginal drug administrations. As revealed in the literature overview, intravaginal products still gain enormous scientific attention, and novel polymers and formulations are still explored. However, there are research areas that require more extensive studies in order to provide the safety of novel vaginal products.

Systematic Development and Characterization of Novel, High Drug-Loaded, Photostable, Curcumin Solid Lipid Nanoparticle Hydrogel for Wound Healing.

The study aims to develop high drug-loaded (about 15% lipid matrix) curcumin solid lipid nanoparticles (CSLNs) for wound healing. CSLNs prepared by hot, high-pressure homogenization, without using organic solvents, were optimized using the Taguchi design followed by the central composite design. The optimized CSLNs exhibited a high assay/drug content (0.6% w/w), solubility (6 × 105 times), and EE (75%) with a particle size < 200 nm (PDI-0.143). The CSLNs were safe (in vitro and in vivo), photostable, autoclavable, stable up to one year at 30 °C and under refrigeration and exhibited a controlled release (zero-order; 5 days). XRD, FTIR, and DSC confirmed solubilization and entrapment of the curcumin within the SLNs. TEM and FESEM revealed a smooth and spherical shape. The CSLNs showed a significant antimicrobial effect (MIC of 64 µg/mL for planktonic cells; 512 µg/mL for biofilm formation; and 2 mg/mL for mature biofilm) against Staphylococcus aureus 9144, while free curcumin dispersion did not exhibit any effect. This is the first report on the disruption of mature biofilms by curcumin solid lipid nanoparticles (CSLNs). The cell proliferation potential of CSLNs was also evaluated in vitro while the wound healing potential of CSLNs (incorporated in a hydrogel) was assessed in vivo. In (i) nitrogen mustard gas and (ii) a full-thickness excision wound model, CSLNs exhibited (a) significantly faster wound closure, (b) histologically and immunohistochemically better healing, (c) lower oxidative stress (LPO) and (d) inflammation (TNFα), and (e) increased angiogenesis (VEGF) and antioxidant enzymes, i.e., catalase and GSH levels. CSLNs thus offer a promising modern wound therapy especially for infected wounds, considering their effects in mature biofilm disruption.

Deodorants and antiperspirants: identification of new strategies and perspectives to prevent and control malodor and sweat of the body.

Excessive sweating and body odors in many cultures can cause negative perceptions of an individual and in many cases is related to poor hygiene. Personal hygiene products have been developed with the intention of preventing these undesirable issues. The aim of this paper is to review the main active ingredients used in marketed deodorant and antiperspirant formulations as well as to identify new strategies and future methods to optimize such products and prevent malodor. PubMed and ScienceDirect databases were used to search for studies reporting the use of deodorants and antiperspirants, the compounds used in the formulations, their mechanisms of action and associated controversies, as well as new trends and approaches in the area. Even today, we are still using well-known and established actives such as triclosan and aluminum salts, and these are still the most used compounds in deodorants with bactericidal and antiperspirant properties. These substances have been on the market for more than 40 years, and still there are many questions concerning the safety of both actives. There is a general increased interest globally for lifestyles that focus on sustainability and more natural products such as plant sources and the use of, for example, essential oils. The research that focuses in the area of antiperspirants and deodorants is now more focused on studies of the armpit biochemistry and function and control of the microbiota present in this area. Other possible areas of interest are biotechnological solutions and finding new compounds that will interfere with the biochemistry of the process of sweat decomposition. Further approaches include formulations with probiotics which would maintain the balance of axillary microbiota.

Nanostructured Non-Ionic Surfactant Carrier-Based Gel for Topical Delivery of Desoximetasone.

Psoriasis is a chronic autoimmune skin disease impacting the population globally. Pharmaceutical products developed to combat this condition commonly used in clinical settings are IV bolus or oral drug delivery routes. There are some major challenges for effectively developing new dosage forms for topical use: API physicochemical nature, the severity of the disease state, and low bioavailability present challenges for pharmaceutical product developers. For non-severe cases of psoriasis, topical drug delivery systems may be preferred or used in conjunction with oral or parenteral therapy to address local symptoms. Elastic vesicular systems, termed "niosomes", are promising drug delivery vehicles developed to achieve improved drug delivery into biological membranes. This study aimed to effectively incorporate a corticosteroid into the niosomes for improving the drug bioavailability of desoximetasone, used to treat skin conditions via topical delivery. Niosomes characterization measurements were drug content, pH, spreadability, specific gravity, content uniformity, rheology, and physicochemical properties. Formulations used a topical gelling agent, Carbomer 980 to test for in vitro skin permeation testing (IVPT) and accelerated stability studies. The developed niosomal test gel provided approximately 93.03 ± 0.23% to 101.84 ± 0.11% drug content with yield stresses ranging from 16.12 to 225.54 Pa. The permeated amount of desoximetasone from the niosomal gel after 24 h was 9.75 ± 0.44 µg/cm2 compared to 24.22 ± 4.29 µg/cm2 released from the reference gel tested. Furthermore, a drug retention study compared the test gel to a reference gel, demonstrating that the skin retained 30.88 ng/mg of desoximetasone while the reference product retained 26.01 ng/mg. A controlled drug release profile was obtained with a niosomal formulation containing desoximetasone for use in a topical gel formulation showing promise for potential use to treat skin diseases like psoriasis.

Microemulsion-Based Media in Nose-to-Brain Drug Delivery.

Nose-to-brain drug delivery has recently attracted enormous attention as an alternative to other delivery routes, including the most popular oral one. Due to the unique anatomical features of the nasal cavity, drugs administered intranasally can be delivered directly to the central nervous system. The most important advantage of this approach is the ability to avoid the blood-brain barrier surrounding the brain and blocking the entry of exogenous substances to the central nervous system. Moreover, selective brain targeting could possibly avoid peripheral side effects of pharmacotherapy. The challenges associated with nose-to-brain drug delivery are mostly due to the small volume of the nasal cavity and insufficient drug absorption from nasal mucosa. These issues could be minimized by using a properly designed drug carrier. Microemulsions as potential drug delivery systems offer good solubilizing properties and the ability to enhance drug permeation through biological membranes. The aim of this review is to summarize the current status of the research focused on microemulsion-based systems for nose-to-brain delivery with special attention to the most extensively investigated neurological and psychiatric conditions, such as neurodegenerative diseases, epilepsy, and schizophrenia.