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Due to rapid urbanization, there have been continuous environmental threats from different pollutants, especially from microplastics. Plastic products rapidly proliferate significantly contributing to the occurrence of micro-plastics, which poses a significant environmental risk. These microplastics originated from diverse sources and are characterized by their persistent and widespread occurrence; human health and the entire ecosystem are adversely affected by them. The removal of microplastics not only requires innovative technologies but also efficient materials capable of effectively eliminating them from our environment. The progress made so far has highlighted the advantages of utilizing the dimensional and structural properties of nanomaterials to increase the effectiveness of existing methods for micro-plastic treatment, aiming for a more sustainable approach to their removal. In the current review, we demonstrate a thorough overview of the sources, occurrences, and potential harmful effects of microplastics, followed by a further discussion of promising technologies used for their removal. An in-depth examination of both advantages and a few limitations of all these given technologies, including physical, chemical, and biological approaches, has been discussed. Additionally, the review explores the use of nanomaterials as an effective means to overcome obstacles and improve the efficiency of microplastic elimination methods. n conclusion, this review addresses, current challenges in this field and outlines the future perspectives for further research in this domain.
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Recuperação e Remediação Ambiental , Microplásticos , Nanoestruturas , Recuperação e Remediação Ambiental/métodos , Microplásticos/química , Nanoestruturas/química , Poluentes Químicos da Água/química , Plásticos/químicaRESUMO
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.
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Periodontitis, the burgeoning disease, is at an alarming stage. Although this has triggered dedicated research in this area, as the disease itself demands a multi-component therapy, there is an unmet need for a compartment and sequential drug delivery system to ameliorate disease symptoms completely. The hypothesized work consists of multitherapeutic agents such as an antibiotic, a COX-II inhibitor, an MMP inhibitor, and a bone regenerating agent in an insitu gel. However, for the development of the system, as mentioned above, a thorough investigation at each stage is necessary; therefore, the quality-by-design approach was adopted. Furthermore, the current work is a pursuit of studying the quality by design aspects for the fabrication of a compartment system, i.e., in-situ gel for periodontal delivery. The proposed system in-situ gel consists of antibiotic and nano-encapsulating microcapsules. Furthermore, the microcapsules contain a COX-II inhibitor and nanoparticles of MMP inhibitor and bone regenerating agent for complete amelioration of periodontitis. To develop the system as per the QbD approach, the first initial trials and runs were conducted, which helped to decide the quality target product profile (QTPP). However, based on QTPP, critical quality attributes (CQA), critical process parameters (CPP), and critical material attributes (CMAs) were decided for each stage product, i.e., in-situ gel, microcapsules, and nanoparticles. To assess the influence of CPPs and CMAs on CQAs, Pareto charts were constructed, and various risks, along with possible failure modes were studied. In conclusion, the above work will serve as a well-designed scientific mouthpiece for developing a compartment system for periodontotherapy.
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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.
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A novel family of multifunctional nanomaterials called MXenes is quickly evolving, and it has potential applications that are comparable to those of graphene. This article provides a current explanation of the design and performance assessment of MXene-based membranes. The production of MXenes nanosheets are first described, with an emphasis on exfoliation, dispersion stability, and processability, which are essential elements for membrane construction. Further, critical discussion is also given to MXenes potential applications in Vacuum assisted filtration, casting method, Hot press method, electrospinning and electrochemical deposition and layer-by-layer assembly for the creation of MXene and MXene derived nanocomposite membranes. Additionally, the discussion is carried forward to give an insight to the modification methods for the construction of MXene-based membrane are described in the literature, including pure or intercalated nanomaterials, surface modifiers and miscellaneous two-dimensional nanomaterials. Furthermore, the review article highlights the potential utilization of MXene and MXene based membranes in separation and purification processes including removal of small organic molecules, heavy metals, oil-water separation and desalination. Finally, the perspective use of MXenes strong catalytic activity and electrical conductivity for specialized applications that are difficult for other nanomaterials to accomplish are discussed in conclusion and future prospectus section of the manuscript. Overall, important information is given to help the communities of materials science and membranes to better understand the potential of MXenes for creating cutting-edge separation and purification membranes.
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Membranas Artificiais , Nanoestruturas , Purificação da Água , Nanoestruturas/química , Purificação da Água/métodos , Grafite/química , Poluentes Químicos da Água/química , Nanocompostos/química , Metais Pesados/química , Filtração/métodosRESUMO
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.
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Menopausa , Osteoporose Pós-Menopausa , Fitoterapia , Humanos , Feminino , Osteoporose Pós-Menopausa/tratamento farmacológico , Menopausa/efeitos dos fármacos , Qualidade de Vida , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
For achieving high effectiveness in the management of breast cancer, coadministration of drugs has attracted a lot of interest as a mode of therapy when compared to a single chemotherapeutic agent that often results in reduced therapeutic end results. Owing to their proven effectiveness, good patient compliance, and lower costs, oral anticancer drugs have received much attention. In the present work, we formulated the chitosan-coated nanoliposomes loaded with two lipophilic agents, namely, exemestane (EXE) and genistein (GEN). The formulation was prepared using the ethanol injection method, which is considered a simple method for getting the nanoliposomes. The formulation was optimized using Box-Behnken design (BBD) and was extensively characterized for particle size, ζ-potential, Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. The sizes of conventional and coated liposomes were found to be 104.6 ± 3.8 and 120.3 ± 6.4 nm with a low polydispersity index of 0.399 and 0.381, respectively. The ζ-potential of the liposomes was observed to be -16.56 mV, which changed to a positive value of +22.4 mV, clearly indicating the complete coating of the nanoliposomes by the chitosan. The average encapsulation efficiency was found to be between 70 and 80% for all prepared formulations. The compatibility of the drug with excipients and complete dispersion of the drug inside the system were verified by FTIR, XRD, and DSC studies. Furthermore, the in vitro release studies concluded the sustained release pattern following the Korsmeyer-Peppas model as the best-fitting model with Fickian diffusion. Ex vivo studies showed better permeation of the chitosan-coated liposomes, which was further confirmed by confocal studies. The prepared chitosan-coated liposomes showed superior antioxidant activity (94.56%) and enhanced % cytotoxicity (IC50 7.253 ± 0.34 µM) compared to the uncoated liposomes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay displayed better cytotoxicity of the chitosan-coated nanoliposomes compared to the plain drug, showing the better penetration and enhanced bioavailability of drugs inside the cells. The formulation was found to be safe for administration, which was confirmed using the toxicity studies performed on an animal model. The above data suggested that poorly soluble lipophilic drugs could be successfully delivered via chitosan-coated liposomes for their effective delivery in breast cancer.
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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.
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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.
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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.
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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.
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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.
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Exemestane (EXE), an irreversible aromatase inhibitor, is employed as a therapy for hormone-dependent breast cancer. Several studies have also established the budding effects of genistein (GEN) in various types of cancer such as breast, prostate, as well as skin due to its feeble estrogenic and anti-estrogenic properties. Considering the promising benefits of GEN, it was combined with EXE to accomplish superior therapeutic efficiency with fewer side effects. The quantification of the exact concentration of EXE and GEN when delivered as a combination would be required for which HPLC method was developed and validated. For this purpose, the C18 ODS column having dimensions of 150 × 4.6 mm, 5 µm, using mobile phase A as methanol:water (35:15, v/v), with formic acid (0.01%), and B as acetonitrile (in the ratio of A:B--30:70 v/v) at a flow rate of 1 mL/min was commonly used. The Box-Behnken design was chosen as our experimental model, and the interactions among the independent and dependent variables were analyzed. Parameters like linearity, system suitability, specificity, precision (intra- and interday), robustness, ruggedness, LOD (limit of detection), and LOQ (limit of quantification) were selected for the validation of our proposed method. EXE and GEN were eluted individually at 245 and 270.5 nm, respectively, while both of the agents were determined simultaneously at 256 nm, showing retention time as 2.10 and 1.67 min, respectively, and the calibration plot was observed to be linear in the range of 5-110 µg/mL. Hence, the method that we developed and validated was found to be suitable for the identification of both the drugs simultaneously in combination and in our in-house-developed nanoformulation.
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Hyaluronic acid (HA) coated irinotecan loaded lignin nanoparticles (HDLNPs) were synthesized using ionic interaction method. Optimized nanoparticles were characterized for their active chemotherapeutic targeting potential to CD44 receptors overly-expressed on cancer cells. Blood component interaction studies supported hemocompatible nature of HDLNPs and also demonstrated their sustained plasma residence property. Cell anti-proliferation and mitochondrial depolarization studies on HT-29 cells suggest significantly (p < 0.01) improved chemotherapeutic efficacy of HDLNPs. In vitro cell based studies showed that nanoparticles have retained antioxidant activity of lignin that can prevent cancer relapse. In vivo biodistribution studies in tumor-bearing Balb/c mice confirmed improved drug localization in tumor site for longer duration. Tumor regression and histopathological studies indicated the efficacy ofligand-assisted targeting chemotherapy over the conventional therapy. Hematological and biochemical estimation suggested that irinotecan-associated myelosuppression, liver steatosis and rare kidney failure can be avoided by its encapsulation in HA-coated lignin nanoparticles. HDLNPs were found to be stable over a period of 12 months.
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Antineoplásicos , Neoplasias do Colo , Nanopartículas , Camundongos , Animais , Irinotecano/farmacologia , Lignina , Distribuição Tecidual , Neoplasias do Colo/tratamento farmacológico , Nanopartículas/química , Ácido Hialurônico/química , Receptores de Hialuronatos/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/químicaRESUMO
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.
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Apigenin is a natural polyphenolic compound widely distributed as a glycoside in fruits and vegetables. Apigenin belongs to BCS class II with low solubility, which leads to poor absorption and bioavailability. It is mostly absorbed from the small intestine and extensively metabolized through glucuronidation and sulfation processes. Apigenin is known for its antioxidant and anti-inflammatory properties. It is also used as a chemopreventive drug in the management of various cancers. Pharmacological effects of apigenin have a wide range, from neuroprotective to treating renal disorders. Apigenin is non-toxic in nature and acts through various pathways (JAK/STAT, Wnt/ß-catenin, MAPK/ERK, PI3K/Akt, and NF-κB) to exert its therapeutic efficacy. Numerous formulations have been researched to enhance the bioavailability and pharmacological effects of apigenin. Combinatorial therapies are also researched to minimize the side-effects of chemotherapeutic drugs. The review presents pharmacokinetic and pharmacodynamic aspects of apigenin. Apigenin is safe for the treatment and management of numerous diseases. It can be easily incorporated into nanoformulation alone or in combination with other active ingredients to widen the therapeutic window. This review intends to help in drug optimization and therapeutic efficacy maximization for future studies.
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Anticarcinógenos , Neoplasias , Humanos , Apigenina/farmacologia , Apigenina/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , NF-kappa B/metabolismo , Neoplasias/tratamento farmacológicoRESUMO
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.
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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.
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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.
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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.