Formulation, Optimization, and Evaluation of Non-Propellent Foam-Based Formulation for Burn Wounds Treatment.

Burn injuries worldwide pose significant health risks due to frequent microbial infections, which worsen complications and increase mortality rates. The conventional antimicrobial formulations are available in the form of ointments and creams. These formulations are very greasy and stick to the clothes. The applications of these formulations by finger or applicator produce pain in the affected area and incur the possibility of microbial infection. To overcome these hurdles, authors developed a novel non-propellent foam (NPF) based formulation containing chlorhexidine for effective topical delivery. Initially, NPF containing Labrasol® (26.7%), sodium lauryl sulfate (1.2%), hydroxy propyl methyl cellulose (0.56%), butylated hydroxytoluene (0.1%), ethanol (1%), and distilled water was prepared and assessed for its consistency, and ability to form foam. The NPF was statistically optimized using the Box-Behnken design to determine the effect of polymer and surfactants on the critical foam properties. The optimized formulation showed a collapse time of 45 s with a unique nature of collapsing upon slight touch which is highly beneficial for burn patients with microbial infection. The diffusion study showed that more than 90% of the drug was released within 6 h. The skin permeation study showed that 23% of the total drug permeated through the skin after 6 h with 7.64 µg/cm2/h permeation flux. The developed formulation showed good antibacterial activity. The minimum inhibitory concentration of prepared NPF was found to be 2.5 µg/mL, 2.5 µg/mL, and 5.0 µg/mL against E. coli (MTCC-1687), P. aeruginosa (MTCC-1688), and S aureus (MTCC-737) respectively. The developed NPF formulation showed quick collapse time, excellent spreadability, good anti-bacterial activity, and a non-sticky nature representing a promising avenue for burn wound treatment without using any applicator.

Fisetin from Dietary Supplement to a Drug Candidate: An Assessment of Potential

Fisetin is a bioactive compound found in numerous fruits and vegetables, including strawberries, apples, grapes, persimmon, cucumber, onion, etc. The compound is also wellknown for its neurotrophic, anti-inflammatory, anti-carcinogenic, anti-diabetic, and other healthpromoting properties. Although there is increasing agreement that it has therapeutic properties, but its poor water solubility, high lipophilicity, and lower oral bioavailability make it difficult to use clinically. Extensive research has attempted to overcome these restrictions by developing novel and superior delivery systems. Considering the diverse potential, this review is the first to summarise the available data on Fisetin to collate the information related to analytical methods, pharmacological action, their mechanisms, regulatory aspects, and toxicity profile. It also covers the marketed products, related clinical trials, and patent updates of the moiety. In addition, an endeavor has been attempted to discuss and assess the various drug delivery systems employed to increase the biological attributes of Fisetin. The presented manuscript is the first to present a compendium of up-to-date literature on all of the domains considered necessary for this type of natural molecule to carve down its path from being a mere dietary supplement to a promising therapeutic drug candidate. The manuscript is expected to benefit the researchers working on natural and bioactive compounds, industrial scientists, and the general population interested in Fesitin.

A Cross-sectional Survey-based Study of Knowledge, Attitude, and Practice Towards Uses of Cosmetics and Cosmetovigilance in India.

Background: In India, the cosmetics industry has expanded significantly because of changing lifestyles and increased awareness. In terms of earning the most money from the personal care and cosmetics industry in 2021, India is ranked fourth globally. Many cosmetics sold in India include ingredients that cannot be used on humans. Objective: To assess knowledge, attitudes, and practice toward the uses of cosmetics and cosmetovigilance in India. Methods: A cross-sectional study was conducted, from April to May 2022, among the general population living in the Delhi NCR region, India. Study questionnaires (printed and survey link) were distributed in public as well as at workplaces for the survey. Results: Around 268 (54.78%) females and 223 (45.21%) males participated in the survey. Amongst the total respondents - 407 (83%) agreed that they are using cosmetic products on a daily basis, females 229 (85.44%), being the majority users compared to males 178 (80%), with a significant P value = 0.011. Most of the people reported side effects of shampoos - 7.13% (hair fall, hair thinning, dryness of the scalp, itching), followed by allergic reactions to moisturizers - 5.70%. Conclusion: Because of the right safety and effectiveness mentorship of cosmetics, regulatory agencies and stakeholders should adopt this broadly. Cosmetovigilance needs to be put into practice.

CTAB Protocol for Obtaining High-Quality Total RNA from Hibiscus rosa-sinensis and Other Related Plants of the Family Malvaceae.

Malvaceae family, also known as the Mallow family, is a family of flowering plants containing Hibiscus rosa-sinensis and other plants of high medicinal value. This study focuses on the challenges associated with high-quality RNA extraction from Hibiscus rosa-sinensis and its related plants characterized by high levels of mucilage and phenolic compounds in their tissues. High mucilage and secondary metabolite content pose obstacles in obtaining high-quality RNA, negatively impacting downstream applications, such as gene expression analysis. Our research aimed to develop an efficient RNA extraction method tailored to the unique characteristics of Malvaceae family plants especially Hibiscus rosa-sinensis. Through the substitution of NaCl with KCl, a crucial component of the CTAB buffer, our methodology successfully addressed the challenges posed by high mucilage and phenolic compound levels. This modification led to a significant reduction in sample viscosity, which is because of the high mucilage in these plants. Our modified CTAB extraction method yielded significantly more RNA with higher purity than the conventional CTAB methods alone. The extracted RNA was largely intact, as indicated by 28S/18S ratios and RIN values, yielding high-quality RNA with improved purity suggested by the 260/280 and 260/230 ratios. The proposed approach not only serves as a solution to the specific challenges encountered in Hibiscus rosa-sinensis but also holds promise for broader applications across different plants within the family.

Phytotherapeutic approach for conquering menopausal syndrome and osteoporosis.

Women face a significant change in their reproductive health as menopause sets in. It is marred with numerous physiological changes that negatively impact their quality of life. This universal, transition phase is associated with menopausal and postmenopausal syndrome, which may spread over 2-10 years. This creates a depletion of female hormones causing physical, mental, sexual and social problems and may, later on, manifest as postmenopausal osteoporosis leading to weak bones, causing fractures and ultimately morbidity and mortality. Menopausal hormone therapy generally encompasses the correction of hormone balance through various pharmacological agents, but the associated side effects often lead to cessation of therapy with poor clinical outcomes. However, it has been noticed that phytotherapeutics is trusted by women for the amelioration of symptoms related to menopause and for improving bone health. This could primarily be due to their reduced side effects and lesser costs. This review attempts to bring forth the suitability of phytotherapeutics/herbals for the management of menopausal, postmenopausal syndrome, and menopausal osteoporosis through several published research. It tries to enlist the available botanicals with their key constituents and mechanism of action for mitigating symptoms associated with menopause as well as osteoporosis. It also includes a list of a few herbal commercial products available for these complications. The article also intends to collate the findings of various clinical trials and patents available in this field and provide a window for newer research avenues in this highly important yet ignored health segment.

An Overview of the Dichotomous Role of Microbiota in Cancer Progression and Management.

It is a well-known fact that cancer is considered the second leading cause of mortality across the globe. Although the human oral cavity and intestine are the natural habitat of thousands of microbes, dysbiosis results in malignancies, such as oral squamous cell carcinoma and colorectal cancer. Amongst the intestinal microbes, H. pylori is a deadly carcinogen. Also, causative pathogens for the development of pancreatic and colorectal cancer are found in the oral cavity, such as Fusobacterium nucleatum and Porphyromonas gingivalis. Many periodontopathic micro- organisms, like Streptococcus sp., Peptostreptococcus sp., Prevotella sp., Fusobacterium sp., Porphyromonas gingivalis, and Capnocytophaga gingivalis, strongly have an impact on the development of oral cancers. Three basic mechanisms are involved in pathogen-mediated cancer development, like chronic inflammation-mediated angiogenesis, inhibition of cellular apoptosis, and release of carcinogenic by-products. Microbiota has a dichotomous role to play in cancer, i.e., microbiota can be used for cancer management too. Shreds of evidence are there to support the fact that microbiota enhances the chemotherapeutic drug efficacy. This review presents the possible mechanism of the oncogenic effect of microbiota with emphasis on the oral microbiome and also attempts to explain the intricate role of microbiota in cancer management.

QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery.

The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate-chitosan nanoparticles and optimized based on particle size and drug content. Optimized formulation was then subjected to different evaluation parameters like encapsulation efficiency, hydroxyapatite content, ζ potential, surface morphology, in vitro drug release, cell line studies, and stability studies. For the optimized formulation, particle size, polydispersity index (PDI), entrapment efficiency, ζ potential, and drug content were found to be 336.50 nm, 0.23, 41.77%, -13.85 mV, and 14.00%, respectively. The surface morphology of the placebo and adsorbed composite-loaded nanoparticles as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the spherical shape and rough surface of the particles. In gingival crevicular fluid (GCF) 7.6, a sustained drug release profile was obtained up to 36 h. In vitro % viability studies performed on murine fibroblast cells (NIH3T3) and human periodontal ligament (hPDL) cell lines confirmed the proliferative nature of the formulation. Also, when subjected to stability studies for 4 weeks, particle size, PDI, and drug content did not vary considerably, thereby ensuring the stable nature of nanoparticles. Henceforth, sodium alginate-chitosan nanoparticles appeared to be a good carrier system for doxycycline hyclate and hydroxyapatite for periodontal therapy. If given along with a system antibiotic, the system will serve as a fruitful tool for infection-mediated periodontal regeneration and healing.

In silico and in vitro assessment of an optimized QbD-guided myoinositol and metformin-loaded mucus-penetrating particle-based gel for the amelioration of PCOS.

Polycystic ovarian syndrome (PCOS) is a multi-factorial endocrine disorder affecting women of reproductive age. However, its high prevalence and the unsuccessful translation of conventional modalities have made PCOS a pharmaco-therapeutic challenge. In the present study, we explored bi-formulations (comprising metformin-loaded mucus-penetrating nanoparticles, MTF-MPPs, and myoinositol-loaded mucus-penetrating particles, MI-MPPs) incorporated in a carbomer gel tailored for intravaginal administration. For the development and optimization of the MPPs-gel, a QbD (quality by design) approach was employed, including the initial and final risk assessment, central composite design of experts, and method validation. The optimized MTF-MPPs and MI-MPPs possessed an optimum nanometric particle size (195.0 nm and 178.8 nm, respectively) and a PDI of 0.150 and 0.123, respectively, together with a negligible negative zeta potential (-5.19 mV and -6.19 mV, respectively) through the vaginal mucus. It was observed that the MPPs are small and monodisperse with a neutral surface charge. It was observed that the MPPs-gel formulations released approximately 69.86 ± 4.65% of MTF and 67.14 ± 5.74% of MI within 120 h (5 days), which was observed to be sustained unlike MFT-MI-gel with approximately 94.89 ± 4.17% of MTF and 90.91 ± 15% of MI drugs released within 12 h. The confocal microscopy study of rhodamine-loaded MPPs indicated that they possessed a high fluorescence intensity at a depth of 15 µm, while as the penetration trajectory in the vaginal tissue increased to 35 µm, their intensity was reduced, appearing to be more prominent in the blood vessels. The analyzed data of MPPs-gel suggest that the optimized MPPs-gel formulation has potential to reach the targeted area via the uterovaginal mucosa, which has a wide network of blood vessels. Subsequently, in vivo studies were conducted and the results revealed that the proposed MPPs-gel formulation could regulate the estrous cycle of the reproductive system compared to the conventional formulation. Moreover, the formulation significantly reduced the weight of the ovaries compared to the control and conventional vaginal gel. Biochemical estimation showed improved insulin and sex hormone levels. Thus, the obtained data revealed that the deep penetration and deposition of MTF and MI on the targeted area through intravaginal delivery resulted in better therapeutic effects than the conventional vaginal gel. The obtained results confirmed the amelioration of PCOS upon treatment using the prepared MPPs-gel formulation. According to the relevant evaluation studies, it was concluded that MPPs-gel was retained in the vaginal cavity for systemic effects. Also, the sustained and non-irritating therapeutic effect meets the safety aspects. This work serves as a promising strategy for intravaginal drug delivery.

Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications-A Review.

Quercetin is the major polyphenolic flavonoid that belongs to the class called flavanols. It is found in many foods, such as green tea, cranberry, apple, onions, asparagus, radish leaves, buckwheat, blueberry, broccoli, and coriander. It occurs in many different forms, but the most abundant quercetin derivatives are glycosides and ethers, namely, Quercetin 3-O-glycoside, Quercetin 3-sulfate, Quercetin 3-glucuronide, and Quercetin 3'-metylether. Quercetin has antioxidant, anti-inflammatory, cardioprotective, antiviral, and antibacterial effects. It is found to be beneficial against cardiovascular diseases, cancer, diabetes, neuro-degenerative diseases, allergy asthma, peptic ulcers, osteoporosis, arthritis, and eye disorders. In pre-clinical and clinical investigations, its impacts on various signaling pathways and molecular targets have demonstrated favorable benefits for the activities mentioned above, and some global clinical trials have been conducted to validate its therapeutic profile. It is also utilized as a nutraceutical due to its pharmacological properties. Although quercetin has several pharmacological benefits, its clinical use is restricted due to its poor water solubility, substantial first-pass metabolism, and consequent low bioavailability. To circumvent this limited bioavailability, a quercetin-based nanoformulation has been considered in recent times as it manifests increased quercetin uptake by the epithelial system and enhances the delivery of quercetin to the target site. This review mainly focuses on pharmacological action, clinical trials, patents, marketed products, and approaches to improving the bioavailability of quercetin with the use of a nanoformulation.

Daidzein from Dietary Supplement to a Drug Candidate: An Evaluation of Potential.

Daidzein (DDZ) is a well-known nutraceutical supplement belonging to the class of isoflavones. It is isolated from various sources such as alfalfa, soybean, and red clover. It demonstrates a broad array of pharmacological/beneficial properties such as cardiovascular exercise, cholesterol reduction, and anticancer, antifibrotic, and antidiabetic effects, which make it effective in treating a wide range of diseases. Its structure and operation are the same as those of human estrogens, which are important in preventing osteoporosis, cancer, and postmenopausal diseases. It is thus a promising candidate for development as a phytopharmaceutical. Addressing safety, efficacy, and physicochemical properties are the primary prerequisites. DDZ is already ingested every day in varying amounts, so there should not be a significant safety risk; however, each indication requires a different dose to be determined. Some clinical trials are already being conducted globally to confirm its safety, efficacy, and therapeutic potential. Furthermore, as a result of its therapeutic influence on health, in order to establish intellectual property, patents are utilized. In light of the vast potential of eugenol, this review presents a detailed data collection on DDZ to substantiate the claim to develop it in the therapeutic category.

GastroPlus- and HSPiP-Oriented Predictive Parameters as the Basis of Valproic Acid-Loaded Mucoadhesive Cationic Nanoemulsion Gel for Improved Nose-to-Brain Delivery to Control Convulsion in Humans.

Oral and parenteral delivery routes of valproic acid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in the brain. A GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in humans. HSPiP software 5.4.08 predicted excipients with maximum possible miscibility of the drug. Based on the GastroPlus and HSPiP program, various excipients were screened for experimental solubility, nanoemulsions, and respective gel studies intended for nasal-to-brain delivery. These were characterized by size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Results showed that in vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively, from both tablets (IR and SR) at 8 h using GastroPlus. The predicted drug access to the portal vein was substantially higher in IR (115 mg) compared to SR (82.6 mg). The plasma drug concentration-time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime sites of the drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested a suitable selection of excipients. The program recommended nasal-to-brain delivery of the drug using a cationic mucoadhesive nanoemulsion. The optimized CVE6 was associated with the optimal size (113 nm), low PDI (polydispersity index) (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7% w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. A penetration study using confocal laser scanning microscopy (CLSM) executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6. This might be attributed to the electrostatic interaction existing between the mucosal membrane and nanoglobules. Thus, cationic nanoemulsions and respective mucoadhesive gels are promising strategies for the delivery of VA to the brain through intransal administration for the treatment of seizures and convulsions.

QbD-Engineered Development and Validation of a RP-HPLC Method for Simultaneous Estimation of Rutin and Ciprofloxacin HCl in Bilosomal Nanoformulation.

In the given study, a new reverse-phase high-performance liquid chromatography (RP-HPLC) method has been reported for the simultaneous estimation of ciprofloxacin hydrochloride (CPX) and rutin (RUT) using quality by design (QbD) approach. The analysis was carried out by applying the Box-Behnken design having fewer design points and less experimental runs. It relates between factors and responses and gives statistically significant values, along with enhancing the quality of the analysis. CPX and RUT were separated on the Kromasil C18 column (4.6 × 150 mm, 5 µm) using an isocratic mobile phase combination of phosphoric acid buffer (pH 3.0) and acetonitrile with the ratio of 87:13% v/v at a flow rate of 1.0 mL/min. CPX and RUT were detected at their respective wavelengths of 278 and 368 nm using a photodiode array detector. The developed method was validated according to guideline ICH Q2 R (1). The validation parameters taken were linearity, system suitability, accuracy, precision, robustness, sensitivity, and solution stability which were in the acceptable range. The findings suggest that the developed RP-HPLC method can be successfully applied to analyze novel CPX-RUT-loaded bilosomal nanoformulation prepared by thin-film hydration technique.

Potential of Lipid-Based Nanocarriers against Two Major Barriers to Drug Delivery-Skin and Blood-Brain Barrier.

Over the past few years, pharmaceutical and biomedical areas have made the most astounding accomplishments in the field of medicine, diagnostics and drug delivery. Nanotechnology-based tools have played a major role in this. The implementation of this multifaceted nanotechnology concept encourages the advancement of innovative strategies and materials for improving patient compliance. The plausible usage of nanotechnology in drug delivery prompts an extension of lipid-based nanocarriers with a special reference to barriers such as the skin and blood-brain barrier (BBB) that have been discussed in the given manuscript. The limited permeability of these two intriguing biological barriers restricts the penetration of active moieties through the skin and brain, resulting in futile outcomes in several related ailments. Lipid-based nanocarriers provide a possible solution to this problem by facilitating the penetration of drugs across these obstacles, which leads to improvements in their effectiveness. A special emphasis in this review is placed on the composition, mechanism of penetration and recent applications of these carriers. It also includes recent research and the latest findings in the form of patents and clinical trials in this field. The presented data demonstrate the capability of these carriers as potential drug delivery systems across the skin (referred to as topical, dermal and transdermal delivery) as well as to the brain, which can be exploited further for the development of safe and efficacious products.

Natural Medicine a Promising Candidate in Combating Microbial Biofilm.

Studies on biofilm-related infections are gaining prominence owing to their involvement in most clinical infections and seriously threatening global public health. A biofilm is a natural form of bacterial growth ubiquitous in ecological niches, considered to be a generic survival mechanism adopted by both pathogenic and non-pathogenic microorganisms and entailing heterogeneous cell development within the matrix. In the ecological niche, quorum sensing is a communication channel that is crucial to developing biofilms. Biofilm formation leads to increased resistance to unfavourable ecological effects, comprising resistance to antibiotics and antimicrobial agents. Biofilms are frequently combated with modern conventional medicines such as antibiotics, but at present, they are considered inadequate for the treatment of multi-drug resistance; therefore, it is vital to discover some new antimicrobial agents that can prevent the production and growth of biofilm, in addition to minimizing the side effects of such therapies. In the search for some alternative and safe therapies, natural plant-derived phytomedicines are gaining popularity among the research community. Phytomedicines are natural agents derived from natural plants. These plant-derived agents may include flavonoids, terpenoids, lectins, alkaloids, polypeptides, polyacetylenes, phenolics, and essential oils. Since they are natural agents, they cause minimal side effects, so could be administered with dose flexibility. It is vital to discover some new antimicrobial agents that can control the production and growth of biofilms. This review summarizes and analyzes the efficacy characteristics and corresponding mechanisms of natural-product-based antibiofilm agents, i.e., phytochemicals, biosurfactants, antimicrobial peptides, and their sources, along with their mechanism, quorum sensing signalling pathways, disrupting extracellular matrix adhesion. The review also provides some other strategies to inhibit biofilm-related illness. The prepared list of newly discovered natural antibiofilm agents could help in devising novel strategies for biofilm-associated infections.

In Vitro and In Vivo Investigation of a Dual-Targeted Nanoemulsion Gel for the Amelioration of Psoriasis.

Psoriasis, due to its unique pathological manifestations and the limited success of existing therapeutic modalities, demands dedicated domain research. Our group has developed nanotherapeutics consisting of bioactives such as Thymoquinone (TQ) and Fulvic acid (FA), which have been successfully incorporated into a Nanoemulsion gel (NEG), taking kalonji oil as oil phase. The composition is aimed at ameliorating psoriasis with better therapeutic outcomes. TQ is a natural bio-active that has been linked to anti-psoriatic actions. FA has anti-inflammatory actions due to its free radical and oxidant-scavenging activity. Our previous publication reports the formulation development of the NEG, where we overcame the pharmaco-technical limitations of combining the above two natural bioactives. In vitro evaluation of the optimized NEG was carried out, which showed an enhanced dissolution rate and skin permeation of TQ. This work furthers the pharmaceutical progression of dual-targeted synergistic NEG to treat psoriasis. A suitable animal model, BALB/c mice, has been used to conduct the in vivo studies, which revealed the effective anti-psoriatic action of TQ. Molecular docking studies corroborated the results and revealed a good binding affinity for both the targets of TNF-α (Tumor necrosis factor) and IL-6 (Interlukin-6). Tissue uptake by Confocal laser scanning microscopy (CLSM), a skin interaction study of the gel formulation, and an antioxidant free radical scavenging assay (1-1 Diphenyl-2-picrylhydrazyl DPPH) were also carried out. It was concluded that the NEG may be effective in treating psoriasis with minimal side effects.

Quality by Design Assisted Optimization and Risk Assessment of Black Cohosh Loaded Ethosomal Gel for Menopause: Investigating Different Formulation and Process Variables.

Black cohosh (Cimicifuga racemosa) (CR) is a popular herb and is medically lauded for ameliorating myriad symptoms associated with menopause. However, its pharmaceutical limitations and non-availability of a patient-compliant drug delivery approach have precluded its prevalent use. Henceforth, the current research premise is aimed at developing an ethosomal gel incorporating triterpene enriched fraction (TEF) obtained from CR and evaluating its effectiveness through the transdermal application. TEF-loaded ethosomes were formulated using solvent injection, optimized and characterised. The optimized ethosomes were then dispersed into a polymeric gel base to form ethosomal gel which was further compared with the conventional gel by in-vitro and ex-vivo experiments. Here, the quality by design (QbD) approach was exploited for the optimization and development of ethosomal gel. The elements of QbD comprising initial risk assessment, design of experimentation (DoE), and model validation for the development of formulation have all been described in detail. The optimized ethosomes (F03) showed a nanometric size range, negative zeta potential and good entrapment. The in vitro release profile of gel revealed a burst release pattern following the Korsmeyer Peppas model having Fickian diffusion. The transdermal flux of ethosomal gel was observed to be more than that of conventional gel. Texture analysis and rheological characterization of the gel, revealed good strength showing shear thinning and pseudoplastic behaviour. The confocal microscope investigation revealed the deeper skin permeation of ethosomal gel than conventional gel. This result was further strengthened by DSC, IR and histological assessment of the animal skin (Wistar rat), treated with the optimized formulation. Conclusively, the implementation of QbD in the formulation resulted in a better understanding of the process and the product. It aids in the reduction of product variability and defects, hence improving product development efficiencies. Additionally, the ethosomal gel was found to be a more effective and successful carrier for TEF than the conventional gel through the transdermal route. Moreover, this demands an appropriate animal study, which is underway, for a stronger outcome.

In Silico Guided Nanoformulation Strategy for Circumvention of Candida albicans Biofilm for Effective Therapy of Candidal Vulvovaginitis.

Candidal vulvovaginitis involving multispecies of Candida and epithelium-bound biofilm poses a drug-resistant pharmacotherapeutic challenge. The present study aims for a disease-specific predominant causative organism resolution for the development of a tailored vaginal drug delivery system. The proposed work fabricates a luliconazole-loaded nanostructured lipid carrier-based transvaginal gel for combating Candida albicans biofilm and disease amelioration. The interaction and binding affinity of luliconazole against the proteins of C. albicans and biofilm were assessed using in silico tools. A systematic QbD analysis was followed to prepare the proposed nanogel using a modified melt emulsification-ultrasonication-gelling method. The DoE optimization was logically implemented to ascertain the effect of independent process variables (excipients concentration; sonication time) on dependent formulation responses (particle size; polydispersity index; entrapment efficiency). The optimized formulation was characterized for final product suitability. The surface morphology and dimensions were spherical and ≤300 nm, respectively. The flow behavior of an optimized nanogel (semisolid) was non-Newtonian similar to marketed preparation. The texture pattern of a nanogel was firm, consistent, and cohesive. The release kinetic model followed was Higuchi (nanogel) with a % cumulative drug release of 83.97 ± 0.69% in 48 h. The % cumulative drug permeated across a goat vaginal membrane was found to be 53.148 ± 0.62% in 8 h. The skin-safety profile was examined using a vaginal irritation model (in vivo) and histological assessments. The drug and proposed formulation(s) were checked against the pathogenic strains of C. albicans (vaginal clinical isolates) and in vitro established biofilms. The visualization of biofilms was done under a fluorescence microscope revealing mature, inhibited, and eradicated biofilm structures.

Exploration of a W/O Nanoemulsion for Antibiofilm Activity against Cariogenic Enterococcus faecalis.

A ciprofloxacin-loaded water-in-oil nanoemulsion (CPX-NE) was prepared and evaluated for the antimicrobial effect against oral biofilms produced by Enterococcus faecalis. CPX-NE was prepared by ultrasonication using functional excipients oleic acid (oil phase), Span 80 (surfactant), and Transcutol P (cosurfactant). Rheological parameters (viscosity = 20 ± 1.24 cp) confirmed optimum values for CPX-NE, a pH of 6.5 ± 0.23 suggested the simulation of CPX-NE with the pH of the mouth cavity, refractive index (1.46 ± 0.22), and % transmittance (92.34 ± 0.02) indicated the isotropic nature of the NE. The droplet size (72.19 ± 1.68 nm), polydispersity index (0.142 ± 0.02), and ζ potential (-28 mV) demonstrated a narrow size distribution and electrostatically stabilized NE. The morphology of the optimized formulation showed uniform spherical nanodroplets, as seen in fluorescence microscopy. In vitro drug release showed an initial burst effect followed by sustained release for 48 h, following Fick's diffusion. The minimum biofilm inhibitory and eradication concentration (MBIC/MBEC) was determined to compare CPX-NE with ciprofloxacin plain drug solution (CPX-PS) for their efficacy. CPX-NE demonstrated a significant inhibitory and eradication effect compared to CPX-PS. It was concluded that the developed CPX-NE has effective antibiofilm activity against E. faecalis and may be useful in the prevention and treatment of dental caries.

Investigation of a Minocycline-Loaded Nanoemulgel for the Treatment of Acne Rosacea.

In the present investigation, a nanoemulgel of minocycline was formulated and optimized for an improved drug delivery and longer retention time in the targeted area. Combining eucalyptus oil, Tween 20, and Transcutol HP, different o/w nanoemulsions were formulated by the oil phase titration method and optimized by pseudo-ternary phase diagrams. The morphology, droplet size, viscosity, and refractive index of the thermodynamically stable nanoemulsion were determined. Furthermore, optimized nanoemulsion was suspended in 1.0% w/v of Carbopol 940 gel to formulate the nanoemulgel, and for this, pH, viscosity, and spreadability were determined and texture analysis was performed. To compare the extent of drug penetration between nanoemulsion and nanoemulgel, ex vivo skin permeation studies were conducted with Franz diffusion cell using rat skin as the permeation membrane, and the nanoemulgel exhibited sustained-release behavior. It can be concluded that the suggested minocycline-containing naoemulgel is expected to treat acne rosacea more effectively.

A Pharmaco-Technical Investigation of Thymoquinone and Peat-Sourced Fulvic Acid Nanoemulgel: A Combination Therapy.

Thymoquinone has a multitude of pharmacological effects and has been researched for a wide variety of indications, but with limited clinical success. It is associated with pharmaco-technical caveats such as hydrophobicity, high degradation, and a low oral bioavailability. A prudent approach warrants its usage through an alternative dermal route in combination with functional excipients to harness its potential for treating dermal afflictions, such as psoriasis. Henceforth, the present study explores a nanoformulation approach for designing a fulvic acid (peat-sourced)-based thymoquinone nanoemulsion gel (FTQ-NEG) for an enhanced solubility and improved absorption. The excipients, surfactant/co-surfactant, and oil selected for the o/w nanoemulsion (FTQ-NE) are Tween 80/Transcutol-P and kalonji oil. The formulation methodology includes high-energy ultrasonication complemented with a three-dimensional/factorial Box-Behnken design for guided optimization. The surface morphology assessment through scanning/transmission electron microscopy and fluorescence microscopy revealed a 100 nm spherical, globule-like structure of the prepared nanoemulsion. Furthermore, the optimized FTQ-NE had a zeta potential of -2.83 ± 0.14 Mv, refractive index of 1.415 ± 0.036, viscosity of 138.5 ± 3.08 mp, and pH of 5.8 ± 0.16, respectively. The optimized FTQ-NE was then formulated as a gel using Carbopol 971® (1%). The in vitro release analysis of the optimized FTQ-NEG showed a diffusion-dominant drug release (Higuchi model) for 48 h. The drug permeation flux observed for FTQ-NEG (3.64 µg/cm2/h) was much higher compared to that of the pure drug (1.77 mg/cm2/h). The results were further confirmed by confocal microscopy studies, which proved the improved penetration of thymoquinone through mice skin. Long-term stability studies of the purported formulation were also conducted and yielded satisfactory results.