From plants to particles: herbal solutions and nanotechnology combating resistant vulvovaginal candidiasis.

Despite having current advanced therapy, vulvovaginal candidiasis (VVC) remains a common yet debated healthcare-associated topic worldwide due to multi-drug resistance Candida species. In our review, we outlined and highlighted upcoming values with scope of existing and emerging information regarding the possibility of using various natural molecules combined with modern technology that shows promising anti-candida activity in VVC. Furthermore, in this review, we compiled herbal drug molecules and their nanocarriers approach for enhancing the efficacy and stability of herbal molecules. We have also summarized the patent literature available on herbal drug molecules and their nanoformulation techniques that could alternatively become a new innovative era to combat resistance VVC.

There is a type of fungi called Candida that is responsible for infections like vulvovaginal candidiasis in the human vagina. Due to resistance of currently available antifungal medicines, there are side effects on the body. Therefore, researchers are studying and preparing natural-based medicine from plants which may provide very good effects on human health. Also, herbal-based medicines have shown evidence based good antifungal activity. Combinations of herbal drugs with very small-sized particles called nanomaterials have added advantage as it helps herbs (drug) to reach their target. Its activity is enhanced as it stays for longer time in the body. So, in the future more research is needed to make sure plant medicines are safe and work well on vaginal infections and its uses should be promoted so that could be a good solution for treating vaginal candidiasis.

Astrocyte Activation and Drug Target in Pathophysiology of Multiple Sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease, which is also referred to as an autoimmune disorder with chronic inflammatory demyelination affecting the core system that is the central nervous system (CNS). Demyelination is a pathological manifestation of MS. It is the destruction of myelin sheath, which is wrapped around the axons, and it results in the loss of synaptic connections and conduction along the axon is also compromised. Various attempts are made to understand MS and demyelination using various experimental models out of them. The most popular model is experimental autoimmune encephalomyelitis (EAE), in which autoimmunity against CNS components is induced in experimental animals by immunization with self-antigens derived from basic myelin protein. Astrocytes serve as a dual-edged sword both in demyelination and remyelination. Various drug targets have also been discussed that can be further explored for the treatment of MS. An extensive literature research was done from various online scholarly and research articles available on PubMed, Google Scholar, and Elsevier. Keywords used for these articles were astrocyte, demyelination, astrogliosis, and reactive astrocytes. This includes articles being the most relevant information to the area compiled to compose a current review.

Potential role of herbal nanoformulations for skin disorders: a review.

Aim: In the recent advanced study, the popularity of herbal nano-formulation has gained around the whole world. As we know the reason behind it is that herbal products have comparatively lesser side effects than other synthetic products. Significance: These natural plant extracts have wide medicinal importance as they increase the overall bioavailability of products toward tissues. Key findings: This review provides the use of different herbal nano-formulations, their safety considerations, and the challenges being faced. It also highlights the various Clinical Trials and Patents that are published for skin disorders. Conclusion: The present review describes how the rise of herbal products has made wider interest in transdermal formulations and improve the overall productivity by preventing various skin disorders.

Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies.

Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (< 90 nm). Zeta potential was measured to be -11.35 mV, signifying the high stability of the oil droplets. In vivo pharmacokinetic evaluation showed a fourfold increase in the bioavailability of TQ-SNEDDS over pure TQ. Furthermore, in a PCM-induced animal model, TQ-SNEDDS demonstrated significant (p < 0.05) hepatoprotective activity compared to pure TQ and silymarin. Reduction in liver biomarker enzymes and histopathological examinations of liver sections further supported the results. In this study, SNEDDS was demonstrated to be an improved oral delivery method for TQ, since it potentiates hepatotoxicity and enhances bioavailability.

Gastric ulcer healing by chebulinic acid solid dispersion-loaded gastroretentive raft systems: preclinical evidence.

Background: Chebulinic acid (CA), a component in Terminalia chebula, exhibits antiulcer activity, but has poor aqueous solubility. Raft-forming systems incorporating solid dispersions (SDs) of CA, were developed to overcome its poor biopharmaceutical properties and to prolong the gastric residence time for maximum activity. Methods: SDs were formulated by a solvent evaporation method using Eudragit EPO. Raft formulations consisted of sodium alginate as a polymer. Results: Release of CA in the dissolution medium was 40%, whereas SDs showed 95.45% release. The CA raft system (20 mg/kg) showed curative efficacy in an alcohol-induced gastric ulcer model and increased protection when compared with omeprazole (10 mg/kg) and CA suspension (20 mg/kg). Conclusion: These studies demonstrated SD raft systems to be a promising approach for antiulcer therapy by CA.

Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne.

Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index < 0.7), nano-range (~357.4 ± 2% nm), transmittance (> 90%), and negative zeta potential (-1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris.

Azelaic acid and Melaleuca alternifolia essential oil co-loaded vesicular carrier for combinational therapy of acne.

Aim: Azelaic acid (AzA), a comedolytic, antibacterial, anti-inflammatory anti-melanogenic agent, prescribed against acne vulgaris is safe on skin. Its combination with another widely used anti-acne agent, tea tree oil (EO) whose delivery is limited by volatility, instability and lipophilicity constraints was attempted. Method: Solvent injection was used to prepare AzA-EO integrated ethosomes. Result: Ethosomes were transformed into carbopol hydrogel, which exhibited pseudo-plastic properties with appreciable firmness, work of shear, stickiness and work of adhesion. The hydrogel showed better permeation and retention characteristics vis-a-vis commercial formulation (AzidermTM), when evaluated in Wistar rat skin. Further, ethosome hydrogel composite was better tolerated with no side effects. Conclusion: The findings suggests that the aforementioned strategy could be a potential treatment used for acne management.

Nanocarriers: more than tour de force for thymoquinone.

Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers.

Efficacy of resveratrol encapsulated microsponges delivered by pectin based matrix tablets in rats with acetic acid-induced ulcerative colitis.

Objectives: The objective of the present work to encapsulate the resveratrol (RES) inside the chitosan-based microsponges, employing the systematic optimization by 33 Box-Behnken design for the colonic targeting.Significance: Enhanced therapeutic efficacy of RES-loaded microsponges and matrix tablets, vis-a-vis pureRES for ulcerative colitis.Methods: RES-loaded microsponges were prepared employing the systematic optimization by 33 Box-Behnken design for the colonic targeting. The best-optimizedRES-loaded microsponge was compressed in the form of a tablet, employing pectin as a matrix-forming material. The encapsulation of RES inside microsponge was confirmed by XRD, DSC and FT-IR. Further, both RES-loaded microsponges and matrix tablets were evaluated for in vitro release kinetics and further evaluated for in vivo ulcerative colitis animal model.Results: Optimization experiments was obtained as the high value of r2 (particle size = 0.9999; %EE = 0.9652; %CDR = 0.9469) inferred excellent goodness of fit. SEM revealed nearly spherical and porous nature of RES-loaded microsponges. The in vitro release kinetic showed zero-order release for RES-loaded microsponges and Korsmeyer-Peppas model for matrix tablets. The pharmacodynamic studies, in ulcerative colitis rat model, indicated better therapeutic efficacy of drug-loaded microsponges and matrix tablets, vis-a-vis pure RES. Thus, the present study advocates the potential of RES based microsponges delivered by pectin based matrix tablet, in the treatment of various colonic disorders.Conclusion: The present study proved that RES-loaded microsponges and matrix tablets based on chitosan and pectin can be the ideal delivery system for colonic delivery of RES.

Novel thymoquinone loaded chitosan-lecithin micelles for effective wound healing: Development, characterization, and preclinical evaluation.

While the wound healing activity of thymoquinone (TQ) is well known, its clinical effectiveness remains limited due to the inherently low aqueous solubility, resulting in suboptimal TQ exposure in the wound sites. To address these problems, TQ loaded chitosan-lecithin micelles for wound healing were prepared and its efficacy was determined in vivo in the excision wound model. Firstly, the co-block polymer of chitosan and soya lecithin was synthesized which has low critical micelle concentration (CMC). Its employment in the development of TQ loaded polymeric micelles by Self-assembly method resulted in the stable polymeric micelle composition having requisite small particle size (<100 nm), narrow size distribution (close to zero) and high entrapment efficiency (98.77 %) of TQ. The designed nano-carriers not only substantially entrapped the drug but also controlled the release rate of TQ. The TQ-polymeric micelle hydrogel exhibited superior wound healing efficacy to the native TQ and Silver Sulphadiazine.

Thymoquinone-loaded lipid vesicles: a promising nanomedicine for psoriasis.

BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model. METHODS: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis. RESULTS: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation. CONCLUSIONS: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.

Thymoquinone a Potential Therapeutic Molecule from the Plant Nigella sativa: Role of Colloidal Carriers in its Effective Delivery.

BACKGROUND: From the past few decades, remarkable awareness has laid on the use of herbal medicines in pharmaceutical research. Thymoquinone (TQ), the main chemical constituent of Nigella Sativa (NS) plant, has been extensively explored, and revealed an array of therapeutic benefits, in different in vitro, and in vivo conditions. This review provides brief outline of the diverse therapeutics actions of TQ, and NS, viz. anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, gastroprotective, hepato-protective, anti-microbial and anti-histaminic. Besides, a special emphasis has given on the use of colloidal drug delivery systems exploited hitherto, for the effective delivery of TQ and NS. OBJECTIVE: The main objective of the review was to include an intensive patent literature, available on TQ and NS, for its usefulness in different therapeutic conditions. METHODS: We embarked an organized search of bibliographic databases for peer-reviewed research literature and patent databases. The characteristics of screened papers were described, and a rational qualitative content analysis approach was applied to analyze the interventions and findings of included studies using a theoretical framework. RESULTS: In the past, various studies have carried out which undoubtedly vouch for the multifarious therapeutic roles of TQ in an array of different diseases. More than 670 research papers and around 50 review articles are available on TQ and NS in PubMed database until now, suggesting its high significance. Around 12 review articles published only on the anticancer potential, while the others on its anti- inflammatory and anti-oxidant potential. Around 120 papers included in the review revealed the therapeutic benefits of TQ. In addition to this, an intensive patent literature is also available on TQ and NS, for its usefulness in different therapeutic conditions. CONCLUSION: The findings of this review confirm the effectiveness of TQ in various pathologies viz. inflammation, cancer, diabetes, gastric, hepatic, microbial and allergies. However, the complete clinical benefit of TQ has not yet been realized, owing to its poor biopharmaceutical properties. Nevertheless, colloidal drug delivery carrier systems, could be impending in bringing forth this potential molecule to reality.

Niosome-based hydrogel of resveratrol for topical applications: An effective therapy for pain related disorder(s).

The present work endeavors for development and evaluation of resveratrol loaded niosomal hydrogel system for its anti-inflammatory action. Niosomes were prepared by thin film hydration and ether injection methods employing Span 80 as a surfactant at three different levels. Best optimized formulation was selected on the basis of entrapment efficiency (% EE), mean particle size, sedimentation volume, and microscopy. The vesicular and spherical nature of the niosomes was confirmed by optical microscopy and transmission electron microscope (TEM). Further, resveratrol entrapped niosomal gel was prepared by gelling in Carbopol 934, and evaluated for pH, viscosity, and in vitro release, employing dialysis membrane method. The in vitro release data after fitting to various models revealed it to follow Korsmeyer-Pappas model. Ex vivo permeation studies witnessed high permeation and deposition of resveratrol in skin when compared to plain resveratrol. Dermatokinetic studies elaborated that niosomal gel enhanced the biological half-life and reduced Tmax of the drug, in both the skin layers. Finally, in vivo anti-inflammatory activity of niosomal gel was evaluated by carrageenan induced paw edema model and compared with standard sodium diclofenac gel. The resveratrol entrapped niosomal gel sufficiently reduced the edema and revealed prolonged therapeutic action vis-a-vis the marketed anti-inflammatory gel formulation. Our findings suggest that a topical drug delivery system using niosomal hydrogel could lead to expansion in the anti-inflammatory use of resveratrol.