Novel Drug Delivery Approaches for the Localized Treatment of Cervical Cancer.

Cervical cancer (CC) is the fourth leading cancer type in females globally. Being an ailment of the birth canal, primitive treatment strategies, including surgery, radiation, or laser therapy, bring along the risk of infertility, neonate mortality, premature parturition, etc. Systemic chemotherapy led to systemic toxicity. Therefore, delivering a smaller cargo of therapeutics to the local site is more beneficial in terms of efficacy as well as safety. Due to the regeneration of cervicovaginal mucus, conventional dosage forms come with the limitations of leaking, the requirement of repeated administration, and compromised vaginal retention. Therefore, these days novel strategies are being investigated with the ability to combat the limitations of conventional formulations. Novel carriers can be engineered to manipulate bioadhesive properties and sustained release patterns can be obtained thus leading to the maintenance of actives at therapeutic level locally for a longer period. Other than the purpose of CC treatment, these delivery systems also have been designed as postoperative care where a certain dose of antitumor agent will be maintained in the cervix postsurgical removal of the tumor. Herein, the most explored localized delivery systems for the treatment of CC, namely, nanofibers, nanoparticles, in situ gel, liposome, and hydrogel, have been discussed in detail. These carriers have exceptional properties that have been further modified with the aid of a wide range of polymers in order to serve the required purpose of therapeutic effect, safety, and stability. Further, the safety of these delivery systems toward vital organs has also been discussed.

Chemometric profiling and anti-arthritic activity of aerial parts of Glinus oppositifolius (L.) Aug. DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Glinus oppositifolius (L.) Aug. DC. belongs to the family Molluginaceae, an annual prostrate herb traditionally used to treat inflammations, arthritis, malarial, wounds, fevers, diarrhoea, cancer, stomach discomfort, jaundice, and intestinal parasites. However, the anti-arthritic activity of the aerial part has still not been reported. AIM OF THE STUDY: To investigate the antioxidant and anti-arthritic activity of G. oppositifolius in Complete Freund's Adjuvant (CFA) induced rats. MATERIALS AND METHODS: The dried aerial parts of this plant material were defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The in vitro anti-arthritic activity of methanolic extract of G. oppositifolius (MEGO) was evaluated in protein denaturation, membrane stabilization, and inhibition of proteinase assay at 25, 50, 100, 200, and 400 µg/ml concentrations. Female Wistar rats were immunized sub-dermally into the right hind paw with 0.1 ml of CFA. Rats were administered with MEGO at doses of 200 and 400 mg/kg once daily for fourteen days after arthritis induction. Assessment of arthritis was performed by measuring paw diameter, arthritic index, arthritic score, body weight, organ weight, and hematological and biochemical parameters, followed by the analysis of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1-beta (IL-1ß), cyclooxygenase-2 (COX-2), interleukin 13 (IL-13) and interleukin 10 (IL-10) and histopathological study. In vivo antioxidant effect was investigated in enzymatic assays. The presence of phytoconstituents was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. In silico molecular docking study of the compounds was carried out against COX-2, IL-1ß, IL-6, and TNF-α using AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer software. RESULTS: MEGO's in vitro anti-arthritic activity showed dose-dependent inhibition of protein denaturation, membrane stabilization, and proteinase inhibition, followed by significant in vivo anti-arthritic activity. The rats treated with MEGO showed tremendous potential in managing arthritis-like symptoms by restoring hematological, biochemical, and histological changes in CFA-induced rats. MEGO (200 and 400 mg/kg) showed a significant alleviation in the levels of hyper expressed inflammatory mediators (TNF-α, IL-1ß, and IL-6) and oxidative stress (SOD, CAT, GSH, and LPO) in CFA-induced rats. Spergulagenin-A as identified by LC-MS analysis, exhibited the highest binding affinity against COX-2 (-8.6), IL-1ß (7.2 kcal/mol), IL-6 (-7.4 kcal/mol), and TNF-α (-6.5 kcal/mol). CONCLUSIONS: Provided with the comprehensive investigation, methanolic extract of G. oppositifolius against arthritic-like condition is a proof of concept that revalidates its ethnic claim. The presence of Spergulagenin-A might be responsible for the anti-arthritic activity.

Spray-Dried Mucoadhesive Re-dispersible Gargle of Chlorhexidine for Improved Response Against Throat Infection: Formulation Development, In Vitro and In Vivo Evaluation.

Drug delivery to the buccal mucosa is one of the most convenient ways to treat common mouth problems. Here, we propose a spray-dried re-dispersible mucoadhesive controlled release gargle formulation to improve the efficacy of chlorhexidine. The present investigation portrays an approach to get stable and free-flowing spray-dried porous aggregates of chlorhexidine-loaded sodium alginate nanoparticles. The ionic gelation technique aided with the chlorhexidine's positive surface charge-based crosslinking, followed by spray drying of the nanoparticle's dispersion in the presence of lactose- and leucine-yielded nano-aggregates with good flow properties and with a size range of about 120-350 nm. Provided with the high entrapment efficiency (87%), the particles showed sustained drug release behaviors over a duration of 10 h, where 87% of the released drug got permeated within 12 h. The antimicrobial activity of the prepared formulation was tested on S. aureus, provided with a higher zone of growth inhibition than the marketed formulation. Aided with an appropriate mucoadhesive strength, this product exhibited extended retention of nanoparticles in the throat region, as shown by in vivo imaging results. In conclusion, the technology, provided with high drug retention and extended effect, could be a potential candidate for treating several types of throat infections.

In-silico, in-vitro and in-vivo Biological Activities of Flavonoids for the Management of Type 2 Diabetes.

In spite of the fact that many medicinal plants have been truly utilized for the management of diabetes all through the world, very few of them have been reported scientifically. Recently, a diverse variety of animal models have been established to better understand the pathophysiology of diabetes mellitus, and new medications to treat the condition have been introduced in the market. Flavonoids are naturally occurring substances that can be found in plants and various foods and may have health benefits in the treatment of neuropathic pain. Flavonoids have also been shown to have an anti-inflammatory impact that is significant to neuropathic pain, as indicated by a decrease in several pro-inflammatory mediators such TNF-, NF-B IL-6, and IL-1. Flavonoids appear to be a viable novel therapy option for macrovasular complications in preclinical models; however, human clinical data is still inadequate. Recently, several in silico, in-vitro and in-vivo aproaches were made to evaluate mechanisms associated with the pathogenesis of diabetes in a better way. Screening of natural antidiabetic agents from plant sources can be analysed by utilizing advanced in-vitro techniques and animal models. Natural compounds, mostly derived from plants, have been studied in diabetes models generated by chemical agents in the majority of research. The aim of this work was to review the available in silico, in-vitro and animal models of diabetes for screening of natural antidiabetic agents. This review contributes to the scientist's design of new methodologies for the development of novel therapeutic agents having potential antihyperglycemic activity.

Development and Evaluation of Dutasteride Nanoemulgel for the Topical Delivery against Androgenic Alopecia.

BACKGROUND: Dutasteride is approximately three times more potent than finasteride in treating alopecia. For reducing systemic exposure to dihydrotestosterone (DHT), researchers have shown special interest in developing topical formulations for treating androgenic alopecia. Dutasteride emulsification may lead to good skin penetration and improved availability in different lipophilic skin environments. OBJECTIVES: This study aimed to encapsulate the drug into the lipidic carrier system for better local availability in the scalp skin, develop and evaluate nanoemulgel of dutasteride to ensure efficient topical administration, and perform the in-vivo activity of the developed gel for improved efficacy against alopecia. METHODS: Dutasteride-loaded nanoemulsion was prepared by a high-speed homogenizer, followed by thickening of the dispersion using Carbopol 934. Skin permeation and accumulation were investigated in the excised skin of male Swiss albino mice. The nanoemulgel was characterized based on pH, stress stability, viscosity, and hardness. RESULTS: The optimized dutasteride-loaded nanoemulsion had a size of 252.33 ± 8.59 nm, PDI of 0.205 ± 0.60, and drug content of 98.65 ± 1.78%. Stress stability was performed was well observed in nanoemulsion formulation. Nanoemulgel evaluation results were as follows: pH 5-6 was desirable for topical application, hardness was 43 gm, and spreadability was 79 gm with in vitro release of nanoemulgel at 91.98% and permeation study at 13.67%. CONCLUSION: The in vivo studies demonstrated the growth of newer hair follicles and increased hair diameter and length in dutasteride-loaded nanoemulgel-treated alopecia animals compared to the marketed sample and testosterone-treated group. Provided with the same and long-term storage stability, the developed formulation is supposed to offer a good option for the topical administration of dutasteride in treating androgenic alopecia.

Metronidazole loaded chitosan-phytic acid polyelectrolyte complex nanoparticles as mucoadhesive vaginal delivery system for bacterial vaginosis.

Bacterial vaginosis (BV) is a recurring infection that is difficult to treat due to the limited bioavailability of antimicrobials. In this study, Metronidazole (MTZ)-loaded chitosan nanoparticles (MCSNP) were synthesized employing phytic acid (PA) as a crosslinking agent for treating bacterial vaginosis. The prepared MCSNPs were characterized for size, shape, surface charge, compatibility, cytotoxicity, biofilm inhibition, and in-vitro/in-vivo antimicrobial activities. Morphological examination revealed that nanoparticles generated from 0.535 % w/v chitosan and 0.112 % w/v PA were non-spherical, discontinuous, and irregular, with zeta potential ranging from 25.00 ± 0.45 to 39 ± 0.7. The results of DSC and XRD demonstrated no change in the physical state of the drug in the finished formulation. The optimized formulation demonstrates a cumulative drug release of about 98 ± 1.5 % within 8 h. Antimicrobial studies demonstrated that the optimized formulation had enhanced efficacy against acid-adapted BV pathogens, with a MIC value of 0.9 ± 0.1 µg/mL. Compared to the MTZ alone, the in-vivo antibacterial results of in the case of developed nanoparticles showed a four-fold reduction in bacterial count in female Swiss albino mice. Based on the experimental findings, it was concluded that MCSNPs, due to their excellent physiochemical and antibacterial properties, could serve as a potential topical alternative for treating BV.

Design and evaluation of antibacterials crosslinked chitosan nanoparticle as a novel carrier for the delivery of metronidazole to treat bacterial vaginosis.

Bacterial vaginosis (BV) is a recurring, chronic infection that is difficult to treat due to the limited bioavailability of antimicrobials within vaginal epithelial cells. Vaginal administration, because of lower dosing and systemic exposure offers a viable option for treating vaginal infections. In this study, Metronidazole-loaded chitosan nanoparticles were synthesised employing borax (BX) or tannic acid (TA) as an antimicrobial crosslinking agent for treating BV. The prepared NPs were characterized for various physical, physicochemical, pharmaceutical, thermal and antibacterial properties. Morphological investigation revealed that nanoparticles prepared from 0.5 % w/v chitosan, 1.2 % w/v BX, and 0.4 % w/v metronidazole (MTZ) were non-spherical, with particle sizes of 377.4 ± 37.3 nm and a zeta potential of 34 ± 2.1 mV. The optimised formulation has MIC values of 24 ± 0.5 and 59 ± 0.5 µg/mL, against Escherichia coli (E.coli) and Candida albicans (C.albicans) respectively. The results of DSC and XRD demonstrated no change in the physical state of the drug in the finished formulation. Under simulated vaginal fluid, the optimised formulation demonstrates a cumulative drug release of about 90 % within 6h. The prepared borax crosslinked NPs exhibit anti-fungal activities by inhibiting ergosterol synthesis. The in-vivo antibacterial data indicated a comparable reduction in bacterial count compared to the marketed formulation in female Swiss albino mice treated with optimised nanoparticles. According to histopathological findings, the prepared nanoparticle was safe for vaginal use. Based on the experimental findings, it was concluded that MBCSNPs, due to their good physiochemical and antimicrobial properties, could serve as a potential topical alternative for treating BV and reducing fungal infection.

Implementation of Quality by Design Approaches for Development and Validation of Reverse-Phase High-Performance Liquid Chromatography Assay Method for Determination of Glycyrrhizin in Nanoformulation.

Glycyrrhizin (GL) is the principal constituent of Glycyrrhiza glabra, having antiallergic, anticancer, anti-inflammatory, and antimicrobial action. The reverse-phase high-performance liquid chromatography (RP-HPLC) analytical method was used to quantitatively estimate GL in a nanoformulation and validated as per International Conference on Harmonization Q2 (R1) standards. A stationary phase of the C18-HL reversed-phase column and a mobile phase of acetonitrile and water were used for effective elution. The chromatographic conditions of RP-HPLC were optimized utilizing a quality-by-design approach to accomplish the required chromatographic separation of GL from its nanoformulation with minimal experimental runs. Optimized RP-HPLC conditions for the assay method consist of acetonitrile (41%) and water, pH 1.8, balanced with phosphoric acid (0.1%) as a mobile phase with a flow rate of 1 mL/min. The retention time was found at 7.25 min, and method validation confirmed its sensitivity, preciseness, accuracy, and robustness.

Nanofibers of Glycyrrhizin/Hydroxypropyl-ß-Cyclodextrin Inclusion Complex: Enhanced Solubility Profile and Anti-inflammatory Effect of Glycyrrhizin.

Despite having a wide range of therapeutic advantages, glycyrrhizin (GL) has few commercial applications due to its poor aqueous solubility. In this study, we combined the benefits of hydroxypropyl ß-cyclodextrin (HP-ßCD) supramolecular inclusion complexes and electrospun nanofibers to improve the solubility and therapeutic potential of GL. A molecular inclusion complex containing GL and HP-ßCD was prepared by lyophilization at a 1:2 molar ratio. GL and hydroxypropyl ß-cyclodextrin inclusion complexes were also incorporated into hyaluronic acid (HA) nanofibers. Prepared NF was analyzed for physical, chemical, thermal, and pharmaceutical properties. Additionally, a rat model of carrageenan-induced hind paw edema and macrophage cell lines was used to evaluate the anti-inflammatory activity of GL-HP-ßCD NF. The DSC and XRD analyses clearly showed the amorphous state of GL in nanofibers. In comparison to pure GL, GL-HP-ßCD NF displayed improved release (46.6 ± 2.16% in 5 min) and dissolution profiles (water dissolvability ≤ 6 s). Phase solubility results showed a four-fold increase in GL solubility in GL-HP-ßCD NF. In vitro experiments on cell lines showed that inflammatory markers like IL-1ß, TNF-α, and IL-6 were significantly lower in GL-HP-ßCD NF compared to pure GL (p < 0.01 and p < 0.05). According to in vivo results, the prepared nanofiber exhibits a better anti-inflammatory effect than pure GL (63.4% inhibition vs 53.7% inhibition). The findings presented here suggested that GL-HP-ßCD NF could serve as a useful strategy for improving the therapeutic effects of GL.

Synergistic Effect of Naringin and Glimepiride in Streptozotocin-induced Diabetic Rats.

Objective Evaluation of the synergistic effect of Naringin and Glimepiride in streptozotocin (STZ)-induced diabetic rats. Methods Wistar rats were chosen and divided into five groups (n=6). STZ was used for the induction of diabetes. The combination of naringin and glimepiride was administered to diabetic rats. The changes in fasting blood sugar, body weight, Hb, HbA1c, and creatinine were evaluated, and urine was collected and the volume was observed. The lipid profiles like TC, HDL, LDL, and TG were measured. The biochemical parameters SGOT, SGPT, and ALP were analysed. Besides, endogenous antioxidant parameters like SOD, GSH, and catalase were also assessed. Lastly, the histopathological study of the beta cells in islets of the pancreas, glomerulus, and tubules of kidney and liver cells was conducted in all groups. Results The result shows significant reduction (p<0.001) of blood sugar in the naringin and glimepiride-treated group when compared with the control group (diabetes). Additionally, the combination of Naringin (100 mg/kg) and Glimepiride (0.1 mg/kg) significantly restores the creatinine levels and urine volumes, SGOT, SGPT, and ALP when compared to a single dose of administration. Further, the abnormal lipid profile levels (TC, LDL, TG, and HDL), and endogenous antioxidant enzymes (SOD, GSH, catalase) in diabetic control rats were restored to normal levels in a significant manner. The histopathological result reveals significant alterations, including hypertrophy of islets and mild degeneration, renal necrosis, and inflammation of hepatocytes. Conclusion A synergistic effect of Naringin and glimepiride was observed during the estimation of various biochemical parameters like body weight, fasting blood sugar, creatinine, urine level, TG, total cholesterol, SGOT, SGPT, ALP, Insulin, HbA1C, antioxidant parameters like SOD, GSH, and catalase in STZ-induced diabetic rats. Further, the combination of therapy improves the protective effect of the pancreas, kidney, and liver, suggesting a potential antidiabetic effect.

Antiviral application of Carbohydrate Polymers: A review.

BACKGROUND: Viral disease is a well-known cause of a significant impact on economic losses and threatens developed and developing societies. High mutation rates and the lack of ability of conventional formulations to target specific cells pose substantial hurdles to the successful treatment of viral diseases.

Methods: We conducted a preliminary search by a standard procedure. With hand searching, we conducted an advanced search across several electronic databases. After defining the selection criteria, two writers independently reviewed and evaluated the first 500 abstracts before screening the remaining 300. Since there was 97% agreement on the screening decisions, only one reviewer conducted the screening. The pre-planned data extraction process was accomplished, and the thoroughness of the description of participation techniques was assessed. Additional data extraction was carried out for articles with the most detailed illustrations. Four stakeholder representatives co-authored this systematic review.

Results: Incorporating selective carbohydrate polymers into the antiviral pharmaceutical compositions could help to manage biological complications associated with viral infections. We included 172 papers in which authors were involved in a systematic review. The present review explains the role of carbohydrate polymers (chitosan, carrageenan, alginate, cyclodextrin, dextran, and heparin) in the prevention and treatment of viral infections in terms of their source, molecular weight, surface charge, chemical composition, and structure. Additionally, the review describes the primary mechanism of drug delivery performance of carbohydrate polymers to improve the antiviral properties and pharmacokinetic behaviour of lamivudine, zidovudine, acyclovir, etc.

Conclusion: The article discussed the role of carbohydrate polymers in mitigating virus-induced associated complications like bacterial infection, cardiovascular disorder, oxidative stress, and metabolic disorder. As a result, this work will provide valuable information to scientists, researchers, and clinicians for suitable carbohydrate polymer-based pharmaceutical development.

Opportunity in nanomedicine to counter the challenges of current drug delivery approaches used for the treatment of malaria: a review.

Malaria is a life-threatening parasitic disease transmitted by the infected female Anopheles mosquito. The development of drug tolerance and challenges related to the drugs' pharmacodynamic and pharmacokinetic parameters limits the antimalarial therapeutics response. Currently, nanotechnology-based drug delivery system provides an integrative platform for antimalarial therapy by improving the drug physicochemical properties, combating multidrug resistance, and lowering antimalarial drug-related toxicity. In addition, surface engineered nanocarrier systems offer a variety of alternatives for site-specific/targeted delivery of antimalarial therapeutics, anticipating better clinical outcomes at low drug concentrations and low toxicity profiles, as well as reducing the likelihood of the emergence of drug resistance. So, constructing nano carrier-based approaches for drug delivery has been considered the foremost strategy to combat malaria. This review focuses on the numerous nanotherapeutic strategies utilised to treat malaria as well as the benefits of nanotechnology as a potentially effective therapeutic.

Recent Advances in Chemical Composition and Transdermal Delivery Systems for Topical Bio-actives in Skin Cancer.

Skin cancer, including basal cell carcinoma, melanoma, and squamous cell carcinoma, is conventionally treated by surgery, phototherapy, immunotherapy, and chemotherapy. For decades, surgical removal of malignant cancers has favored patients' therapeutic options. However, multiple aspects, such as the patient's comorbidities, the anatomical location of the lesion, and possible resistance to recurrent excisions, can influence the decision to conduct surgery. Therefore, topical and transdermal therapy may be a more appropriate option, allowing for higher therapeutic levels at the site of action and reducing toxicity than systemic therapy. The most commonly used topical agents for treating skin carcinoma are- 5-fluorouracil, imiquimod, sonidegib, dacarbazine, etc. However, physicochemical drug characteristics and skin physiological barriers limit the anticancer potency of topical as well as transdermal drug delivery. In recent years, unquestionable signs of progress have been demonstrated to circumvent these challenges. In particular, significant studies have been made, including modification of bio-actives, permeability enhancers, incorporation of advanced nano and microcarriers, and physical enhancement devices. This critical review summarizes the advancement in the chemical composition of bioactives used in skin cancer, such as sinecatechins, BIL-010t, patidegib, gingerol, curcumin, remetinostat, epigallocatechin-3-gallate, etc. Furthermore, this review specifically addresses the progress in transdermal delivery systems for melanoma and nonmelanoma cancer therapy, emphasizing advances in physical and chemical penetration enhancement and nanocarrier-assisted transdermal systems.

Phytochemical investigation, structural elucidation, in silico study and anti-psoriatic activity of potent bioactive from Betula utilis.

Psoriasis is a chronic autoimmune pathological condition characterized by hyperactivation of proinflammatory cytokines (IL-6, TNF-α, IL-17, IL-23, etc.). Severe drug-associated toxicities like hepatotoxicity and nephrotoxicity (Methotrexate), teratogenicity (Tazarotene), hypercholesterolemia (Cyclosporine) and hypercalcemia (tacalcitol), are the forefront challenges that demand an alternative approach for the treatment of psoriasis. In the present study, a natural lead molecule 'Betulin' (BE, lup-20(29)-ene-3b,28-diol) was isolated from Betula utilis and subsequently, structure-based molecular docking was employed to identify the molecular target for psoriasis. The computational analysis reflects better affinity of BE towards pro-inflammatory cytokine as compared to standard drugs. Apart from this BE shows a greater affinity towards the overexpressed Glut-1 receptor in comparison to standard drug Metformin (Met). Based on the in silico screening the isolated lead compound was further processed for the evaluation of anti-psoriatic activity via imiquimod (IMQ 5%) induced psoriasis-like skin inflammation model. In vivo screening models were characterized by different parameters (psoriasis area and severity index (PASI) scores, macroscopically and behavioral evaluation, splenomegaly, cytokine levels and histological changes) and compared among the experimental groups. The experimental finding reflects comparable results of PASI score, i.e., 57.14% and 61.9% recovery of test BE-solution (180 mg/kg) and standard Betamethasone di-propionate ointment (BD-oint.0.5 mg/g), respectively. Focusing on other parameters, BE shows relative results such as an enhanced macroscopically with behavioral conditions, reducing the expression of proinflammatory cytokine as well as restoring histological changes with that of BD. These findings suggest that BE-isolated phytoconstituents from Betula utilis could be a potential agent and a step closer to psoriasis treatment. HIGHLIGHTPsoriasis is a multifaceted, immunologically mediated disease consequences production of high levels of proinflammatory mediators and overexpression of Glut-1 transporters that trigger keratinocyte proliferation and inflammatory cascades.A Himalayan silver birch, Betula utilis (Bhojpatra) contains many steroidal terpenes which are responsible for various pharmacological activities that could be exploited in drug development in psoriasis.The computational analysis of BE reflects a better affinity toward the proinflammatory cytokines with their target receptors and indicates a satisfactory range with a slight deviation from Jorgensen and Lipinski's rule and possesses a significant drug choice for psoriasis.Preclinical findings of BE-solution (BE-sol) give a positive response towards IMQ-induced psoriasis-like skin inflammation model.[Figure: see text]Communicated by Ramaswamy H. Sarma.

Chitosan as a potential biomaterial for the management of oral mucositis, a common complication of cancer treatment.

Oral mucositis is a serious issue in patients receiving oncological therapies. Mucosal protectants considered to be one of the preferred choices used in the management of mucositis. However, the protective efficacy of currently available mucosal protectants has been significantly compromised due to poor retention, lack of lubrication, poor biodegradability, and inability to manage secondary complications. Chitosan is a promising material for mucosal applications due to its beneficial biomedical properties. Chitosan is also anti-inflammatory, anti-microbial, and capable of scavenging free radicals, makes it a good candidate for the treatment of oral mucositis. Additionally, chitosan's amino polysaccharide skeleton permits a number of chemical alterations with better bioactive performance. This article provides a summary of key biological properties of chitosan and its derivatives that are useful for treating oral mucositis. Current literature evidence shows that Chitosan has superior mucosal protective properties when utilised alone or as delivery systems for co-encapsulated drugs.

Current Treatment Strategies Against Multidrug-Resistant Bacteria: A Review.

There are several bacteria called superbugs that are resistant to multiple antibiotics which can be life threatening specially for critically ill and hospitalized patients. This article provides up-to-date treatment strategies employed against some major superbugs, like methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, vancomycin-resistant Enterococcus, multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Escherichia coli. The pathogen-directed therapeutics decrease the toxicity of bacteria by altering their virulence factors by specific processes. On the other hand, the host-directed therapeutics limits these superbugs by modulating immune cells, enhancing host cell functions, and modifying disease pathology. Several new antibiotics against the global priority superbugs are coming to the market or are in the clinical development phase. Medicinal plants possessing potent secondary metabolites can play a key role in the treatment against these superbugs. Nanotechnology has also emerged as a promising option for combatting them. There is urgent need to continuously figure out the best possible treatment strategy against these superbugs as resistance can also be developed against the new and upcoming antibiotics in future. Rational use of antibiotics and maintenance of proper hygiene must be practiced among patients.

Metal nanoparticles against multi-drug-resistance bacteria.

Antimicrobial-resistant (AMR) bacterial infections remain a significant public health concern. The situation is exacerbated by the rapid development of bacterial resistance to currently available antimicrobials. Metal nanoparticles represent a new perspective in treating AMR due to their unique mechanisms, such as disrupting bacterial cell membrane potential and integrity, biofilm inhibition, reactive oxygen species (ROS) formation, enhancing host immune responses, and inhibiting RNA and protein synthesis by inducing intracellular processes. Metal nanoparticles (MNPs) properties such as size, shape, surface functionalization, surface charges, and co-encapsulated drug delivery capability all play a role in determining their potential against multidrug-resistant bacterial infections. Silver, gold, zinc oxide, selenium, copper, cobalt, and iron oxide nanoparticles have recently been studied extensively against multidrug-resistant bacterial infections. This review aims to provide insight into the size, shape, surface properties, and co-encapsulation of various MNPs in managing multidrug-resistant bacterial infections.

Trends in iron oxide nanoparticles: a nano-platform for theranostic application in breast cancer.

Breast cancer (BC) is the deadliest malignant disorder globally, with a significant mortality rate. The development of tolerance throughout cancer treatment and non-specific targeting limits the drug's response. Currently, nano therapy provides an interdisciplinary area for imaging, diagnosis, and targeted drug delivery for BC. Several overexpressed biomarkers, proteins, and receptors are identified in BC, which can be potentially targeted by using nanomaterial for drug/gene/immune/photo-responsive therapy and bio-imaging. In recent applications, magnetic iron oxide nanoparticles (IONs) have shown tremendous attention to the researcher because they combine selective drug delivery and imaging functionalities. IONs can be efficaciously functionalised for potential application in BC therapy and diagnosis. In this review, we explored the current application of IONs in chemotherapeutics delivery, gene delivery, immunotherapy, photo-responsive therapy, and bio-imaging for BC based on their molecular mechanism. In addition, we also highlighted the effect of IONs' size, shape, dimension, and functionalization on BC targeting and imaging. To better comprehend the functionalization potential of IONs, this paper provides an outline of BC cellular development. IONs for BC theranostic are also reviewed based on their clinical significance and future aspects.Graphical Abstract[Formula: see text].

Current Breast cancer treatment resists due to the development of drug tolerance throughout cancer treatment and non-specific drug targeting.Magnetic IONs are being utilised for the therapy and bio-imaging of breast cancer by targeting overexpressed biomarkers, proteins, and receptors in breast cancer progression.Physical properties of IONs, such as size, shape, and dimensions, also alter their therapeutic and imaging responses.Iron oxide nanoparticles can be efficaciously functionalised based on breast cancer molecular mechanisms for potential application in breast cancer drug delivery, gene delivery, immunotherapy, photo responsive therapy, and bio-imaging.

Exploring the Potential of Metal Nanoparticles as a Possible Therapeutic Adjunct for Covid-19 Infection.

The WHO has declared the Covid-19 outbreak as a global health emergency with a mortality rate of approximately 3%, across 200 countries. There has been a considerable risk involved with drug repurposing in Covid-19 treatment, particularly in patients with underlying chronic disorders. Intervention of appropriate adjunct to primary drug therapy at subclinical or clinical doses may help to reduce unintended consequences involved in Covid-19 therapy. Metal nanoparticles due to their intrinsic structural and functional properties, not only contribute to anti-viral properties but also help to reduce the risk for associated complications. Although, silver nanoparticles hold great promise as an effective biocidal agent, while other metal nanoparticles also fueled interest against virus infection. The present review discusses the important properties of selected metal nanoparticles, their antiviral principle with possible toxic consequences, provides invaluable information for scientists and clinicians about an appropriate metal nanoparticle as an adjunct for Covid-19 treatment.

Antidiabetic and antihyperlipidemic effects of Premna spinosa bark in experimental animal models.

The purpose of the study is to evaluate the antidiabetic and hyperlipidemic potential of stem bark extract of Premna spinosa (Lamiaceae), by using streptozotocin (STZ)-nicotinamide (NA)-induced diabetic and triton-induced hyperlipidemic models in albino rats. The blood glucose, total cholesterol, and triglyceride levels were determined in STZ-NA-induced diabetic and triton-induced hyperlipidemic rats, as per the respective protocols. It was found that there is the dose dependent and significant reduction in foregoing parameters on the administration of extract from Premna spinosa stem bark at the doses of 200, 400, and 800 mg/kg body weight to diabetic and hyperlipidemic rats. From these observed results it may be inferred that the stem bark of Premna spinosa possesses remarkable antidiabetic and antihyperlipidemic properties.