Exploring Nose to Brain Nano Delivery for Effective Management of Migraine.

Migraine is a disabling disease characterized by severe throbbing headaches. Patients demand quick relief from this pain. The presence of the blood-brain barrier does not permit the drug to penetrate the brain effectively. Administration of conventional anti-migraine medications via oral route leads to erratic absorption of drugs. Delayed gastric emptying is also responsible for the ineffective absorption of the drug. Migraine-induced nausea and vomiting further limit patient compliance to oral medication. Other limitations associated with the oral route include extensive first-pass metabolism, slow onset of action, inability to cross the blood-brain barrier, requirement of a large amount of dose/dosage, and frequent administration. The anti-migraine drugs used in migraine, such as triptans, are therapeutically effective but have low bioavailability on oral administration. Also, these drugs are associated with several cardiovascular complications. The oral dose of most antimigraine drugs, oral triptans, Ergotamine, NSAIDs, and CGRP antagonists is quite high because of their poor bioavailability. As a result, these drugs are associated with several side effects. This aspect necessitates the need to develop a dosage form that can deliver drugs directly to the brain, thereby reducing the dose. Invasive techniques to deliver these therapeutics to the brain do exist. However, they are painful, require expert assistance, and are not a cost-effective approach for migraine treatment. These limitations demand the development of a novel non-invasive approach that is safe, efficacious, and has high patient compliance. According to reports, it is possible to target the brain tissue by administering the drug intranasally using the olfactory and the trigeminal pathway. This route is non-invasive, avoids first-pass metabolism, eliminates nausea and vomiting, helps reduce dose, and thus helps achieve increased patient compliance. Some factors like solubility, the lipophilicity of the drug, mucociliary clearance, and enzymatic degradation hinder the bioavailability of the drug by nasal route. Therefore, there is a grave need to develop novel nasal formulations with prolonged nasal residence time, which can modulate pharmacokinetics for adequate therapeutic response and render efficient yet robust brain targeting. Considering these challenges, developing an efficient intranasal dosage form is necessary. This review gives a brief overview of all the novel carriers reported for improving the treatment of migraine. Nanocarrier-based delivery systems like in situ gels, microemulsion, nanoemulsion, nanoparticles, vesicular systems, micelles, and microspheres used in nose to brain delivery of migraine therapeutics are also discussed in the article.

Emerging topical drug delivery approaches for the treatment of Atopic dermatitis.

BACKGROUND: Atopic dermatitis is a chronic, relapsing skin inflammation disease that generally affects 20% of children and 1-3% of adults. It is characterized by pruritus, inflammatory skin lesions, and skin barrier defect. The pillar treatment is topical therapies that have shown great adherence and incredible results in alleviating symptoms of atopic dermatitis. Topical corticosteroids and calcineurin inhibitors have shown improvement in the symptoms of atopic dermatitis but have certain side effects. There is need to develop new therapies or novel drug delivery approaches which can overcome drawbacks of the conventional formulation and increase the therapeutic efficacy. AIM: The scope of this review is to describe the new topical therapies including phosphodiesterase inhibitors, Janus kinase inhibitors, and nano-formulations such as nanoemulsion, polymeric and lipid nanoparticles, vesicular system, and micelles. METHODS: The article reviews and discusses the published literature of the topical drug delivery approaches for treatment of Atopic dermatitis. RESULTS: The reported literature highlighted the benefits of novel topical formulations exhibiting targeted drug delivery, better penetration, enhanced therapeutic efficacy, and overcome systemic side effects. CONCLUSION: Literature indicated that the new therapies and novel drug delivery approaches found to be the therapeutically more effective in increasing the efficacy of drugs and reducing the side effects in comparison with the conventional treatments for Atopic dermatitis. This has provided a way to modify and develop more such formulations for dermal delivery.

Alternative Wound Management: Translating Science into Practice.

GENERAL PURPOSE: To present a scoping review of preclinical and clinical trial evidence supporting the efficacy and/or safety of major alternative wound care agents to summarize their effects on validated elements of wound bed preparation and wound management paradigms. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Differentiate the effectiveness of the topical wound care agents included in this review.2. Compare the preventive efficacy of intravenous agents administered to trauma and surgical patients.3. Select the effectiveness of products in this review that are left in place after surgical procedures.4. Identify an oral agent that can be helpful in mitigating the effects of COVID-19.

Effective wound healing is achieved by well-timed host, cell, and environment interactions involving hemostasis, inflammation, formation of repaired dermal structures, and epithelialization, followed by months to years of scar remodeling. Globally, various natural or synthetic agents or dressings are used to optimize wound environments, prolong drug release, aid in fluid absorption, provide favorable healing environments, and act as a mechanical barrier against wound trauma. In this scoping review of evidence from the PubMed and clinicaltrials.gov databases, authors examined clinical study evidence supporting the efficacy and safety of selected phytochemicals, vehicles, polymers, and animal products considered "naturally derived" or "alternative" wound interventions to provide a summary of preclinical evidence. Agents with the most clinical evidence were honey, alginates, polyurethane, gelatin, and dextran. Practice implications are described in the context of the TIMERS clinical paradigm.

Novel user-friendly night care spray to manage skin darkening.

BACKGROUND: Hyperpigmentation can be either diffused or localized. In treating diffused hyperpigmentation, larger surface area coverage is the requirement. Novel user-friendly spray formulation loaded with depigmenting agents can cater the night time need in treating skin darkening. Kojic acid and arbutin, the selected actives for the study exhibit low permeability and high irritancy generating hurdles in topical delivery. AIM: The aim of this study was to develop novel kojic acid and arbutin-loaded spray formulation as a night care product. METHODS: "Thermosensitive gel spray" was fabricated by simple industry feasible cooling technique and evaluated for its ability to improve skin retention, penetration, improved anti-tyrosinase activity, and suppressed dermal irritancy. RESULTS: Comparative in-vitro and ex-vivo release profile showed the marked effect of poloxamer 407 and Methocel K100M in improving penetration and extending release over longer time period. Retention of actives in the skin layer was found to be eight times more in case of thermosensitive gel spray as compared to conventional gel formulation. The thermosensitive gel spray was free from any dermal irritancy and had higher tyrosinase inhibitory effect as against conventional gel. Furthermore, thermosensitive gel spray exhibited good stability and did not show any change in morphology and drug content during the 3-month storage. CONCLUSION: Kojic acid and arbutin-loaded thermosensitive gel spray can prove to be a promising strategy to treat hyperpigmentation.

Advances in encapsulated dermal formulations in chemoprevention of melanoma: An overview.

BACKGROUND: The three forms of skin cancer are cutaneous malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. Melanoma skin cancer is an aggressive type and one of the most chemotherapy-resistant malignancies. Conventional topical products are beset with limitations, leading to lower efficacy. There is a growing need to develop topical formulations encapsulated in polymeric and lipid nanoparticles, nanoemulsions, dendrimers, and liposomes exhibiting enhanced skin penetration and longer skin retention leading to better efficacy. OBJECTIVE: The objective of this article is the screening of reported novel drug encapsulated delivery systems effective topically in melanoma chemoprevention. AIM: The scope of this work is to provide an overview pertaining to the development and evaluation of three exemplary drug delivery systems (DDS), namely vesicular, particulate, and specialized emulsions. METHODS: Topical drug delivery approaches targeting skin cancer have been reviewed and discussed. The focal point of the article is presentation of insights from published studies. RESULTS: This review focuses on the novel delivery systems in chemoprevention of melanoma with discussion highlighting on advances in topical delivery. CONCLUSION: Literature indicates that drug-loaded encapsulated topical formulations when compared with conventional dosage forms for skin cancer treatment exhibit greater efficacy and provide benefits like extended drug release, protection of the active ingredient against degradation, and lower skin irritation. Incorporation of phytoconstituents in newer delivery systems will be the way forward for improved topical chemoprevention strategy in melanoma. This has raised hope in making dermal therapy more useful and acceptable.

Skin delivery of resveratrol encapsulated lipidic formulation for melanoma chemoprevention.

Objective: An unmet need for patient friendly products can be achieved with novel, biocompatible lipidic formulations which encapsulate and prolong release of medicaments. The aim of this study was to develop a commercially scalable resveratrol-loaded solid-lipid microparticulate (SLM) topical gel for melanoma chemoprevention. Methods: Preformulation studies were conducted and drug-excipient interactions examined using infra-red spectroscopy and differential scanning calorimetry (DSC). Resveratrol-loaded SLM topical gel was prepared and evaluated by in vitro and in vivo parameters. Results: Spherical microparticles of 2.98 µm average size were obtained and DSC thermograms provide evidence of trans-resveratrol encapsulation. In vitro and ex vivo drug diffusion studies revealed sustained release profiles. Optimised SLM gel provides optimum antioxidant, tyrosinase inhibition, cytotoxicity in B16F10 melanoma cell line and apoptosis efficacy. In vivo studies on C57BL mice exhibit significant tumour reduction. Conclusion: Promising role of trans-resveratrol-loaded SLM topical gel in melanoma chemoprevention is proven.

An overview of herbal alternatives in androgenetic alopecia.

The second most common alopecia-Androgenetic alopecia (AGA)-occurs due to hormonal imbalance. Dihydrotestosterone (DHT) an androgenic hormone is a sex steroid, produced in the gonads. The target sites of DHT are similar to that of testosterone, and it attaches easily remaining bound for 53 minutes as compared to 35 minutes of testosterone. Excess of DHT causes miniaturization of hair reducing the anagen phase and increasing the telogen phase leading to hair loss. Normally up to ten percent of testosterone in the body irreversibly gets converted into DHT by the action of enzyme 5-alpha-reductase. Inadequate blood flow to the scalp can also be another reason for hair loss encountered due to lower oxygen and nutrients reaching it. AGA affects both sexes; however in males, it leads to major hair loss. Conventional drugs such as minoxidil and finasteride are widely used for the treatment. However, several drawbacks such as allergic contact dermatitis, burning, ejaculation disorder, and decreased libido are reported. Available literature suggests the role of herbal drugs to have the action against 5-alpha-reductase enzyme inhibiting it and reducing the hair loss. This can be further potentiated since they exhibit lesser side effects. Recent advancements observed in the medicinal, cosmetic, and engineering fields can prove to be an asset. This article focuses on herbs which can be used in AGA. A review of Saw palmetto (Serenoa repens), Green tea (Camellia sinensis), Pumpkin seed (Curcurbita pepo), Rosemary (Rosmarinus officinalis), Grape seed (Vitis vinifera), and Licorice (Glycyrrhiza glabra) is attempted.