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.

Radiation therapy margin reduction for patients with localized prostate cancer: A prospective study of the dosimetric impact and quality of life.

OBJECTIVES: To investigate the impact of reducing Clinical Target Volume (CTV) to Planning Target Volume (PTV) margins on delivered radiation therapy (RT) dose and patient reported quality-of-life (QOL) for patients with localized prostate cancer. METHODS: Twenty patients were included in a single institution IRB-approved prospective study. Nine were planned with reduced margins (4 mm at prostate/rectum interface, 5 mm elsewhere), and 11 with standard margins (6/10 mm). Cumulative delivered dose was calculated using deformable dose accumulation. Each daily CBCT dataset was deformed to the planning CT (pCT), dose was computed, and accumulated on the resampled pCT using a parameter-optimized, B-spline algorithm (Elastix, ITK/VTK). EPIC-26 patient reported QOL was prospectively collected pre-treatment, post-treatment, and at 2-, 6-, 12-, 18-, 24-, 36-, 48-, and 60-month follow-ups. Post -RT QOL scores were baseline corrected and standardized to a [0-100] scale using EPIC-26 methodology. Correlations between QOL scores and dosimetric parameters were investigated, and the overall QOL differences between the two groups (QOLMargin-reduced -QOLcontrol ) were calculated. RESULTS: The median QOL follow-up length for the 20 patients was 48 months. Difference between delivered dose and planned dose did not reach statistical significance (p > 0.1) for both targets and organs at risk between the two groups. At 4 years post-RT, standardized mean QOLMargin-reduced -QOLcontrol were improved for Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, and Sexual EPIC domains by 3.5, 14.8, 10.2, and 16.1, respectively (higher values better). The control group showed larger PTV/rectum and PTV/bladder intersection volumes (7.2 ± 5.8, 18.2 ± 8.1 cc) than the margin-reduced group (2.6 ± 1.8, 12.5 ± 8.3 cc), though the dose to these intersection volumes did not reach statistical significance (p > 0.1) between the groups. PTV/rectum intersection volume showed a moderate correlation (r = -0.56, p < 0.05) to Bowel EPIC domain. CONCLUSIONS: Results of this prospective study showed that margin-reduced group exhibited clinically meaningful improvement of QOL without compromising the target dose coverage.

Development of Betulin-Loaded Nanostructured Lipid Carriers for the Management of Imiquimod-Induced Psoriasis.

Psoriasis is a complex and persistent autoimmune skin disease. The present research focused on the therapeutic evaluation of betulin-loaded nanostructured lipid carriers (BE-NLCs) towards managing psoriasis. The BE-NLCs were synthesized using the emulsification cum solidification method, exhibiting a spherical shape with a particle size of 183.5±1.82nm and a narrow size distribution window (PDI: 0.142±0.05). A high zeta potential -38.64±0.05mV signifies the relative stability of the nano-dispersion system. BE-NLCs show a drug loading and entrapment efficiency of 47.35±3.25% and 87.8±7.86%, respectively. In vitro release study, BE NLCs show a cumulative percentage release of 90.667±5.507% over BE-sol (57.334±5.03%) and BD-oint (42±4.58%) for 720min. In an ex vivo 24-h permeation study, % cumulative amount permeated per cm2 was found to be 55.667±3.33% from BE-NLCs and 32.012±3.26% from BE-sol, demonstrating a better permeability of 21.66% when compared to the standard formulation BD-oint. The in vivo anti-psoriatic activity in the IMQ-induced model shows topical application of BE-sol, BE-NLCs, and BD-oint resulted in recovery rates of 56%, 82%, and 65%, respectively, based on PASI (Psoriasis Area and Severity Index) score. Notably, BE-NLCs demonstrated a more significant reduction in spleen mass, indicating attenuation of the local innate immune system in psoriatic mice. Reductions in TNF-α, IL-6, and IL-17 levels were observed in both BE-sol and BE-NLCs groups compared to the disease control (DC) group, with BE-NLCs exhibiting superior outcomes (74.05%, 44.76%, and 49.26% reduction, respectively). Soy lecithin and squalene-based NLCs could be better carrier system for the improvement of the therapeutic potential of BE towards management of psoriasis.

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.

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.

Exploring the Biofilm Inhibition Potential of a Novel Phytic Acid-Crosslinked Chitosan Nanoparticle: In Vitro and In Vivo Investigations.

The primary factor underlying the virulence of Candida albicans is its capacity to form biofilms, which in turn leads to recurrent complications. Over-the-counter antifungal treatments have proven ineffective in eliminating fungal biofilms and the inflammatory cytokines produced during fungal infections. Chitosan nanoparticles offer broad and versatile therapeutic potential as both antifungal agents and carriers for antifungal drugs to combat biofilm-associated Candida infections. In our study, we endeavoured to develop chitosan nanoparticles utilising chitosan and the antifungal crosslinker phytic acid targeting C. albicans. Phytic acid, known for its potent antifungal and anti-inflammatory properties, efficiently crosslinks with chitosan. The nanoparticles were synthesised using the ionic gelation technique and subjected to analyses including Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised nanoparticles exhibited dimensions with a diameter (Dh) of 103 ± 3.9 nm, polydispersity index (PDI) of 0.33, and zeta potential (ZP) of 37 ± 2.5 mV. These nanoparticles demonstrated an antifungal effect with a minimum inhibitory concentration (MIC) of 140 ± 2.2 µg/mL, maintaining cell viability at approximately 90% of the MIC value and reducing cytokine levels. Additionally, the nanoparticles reduced ergosterol content and exhibited a 62% ± 1.2 reduction in biofilm susceptibility, as supported by colony-forming unit (CFU) and XTT assays-furthermore, treatment with nanoparticles reduced exopolysaccharide production and decreased secretion of aspartyl protease by C. albicans. Our findings suggest that the synthesised nanoparticles effectively combat Candida albicans infections. In vivo studies conducted on a mouse model of vaginal candidiasis confirmed the efficacy of the nanoparticles in combating fungal infections in vivo.

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.

Nanotherapeutics approaches to overcome P-glycoprotein-mediated multi-drug resistance in cancer.

Multidrug resistance (MDR) in cancer chemotherapy is a growing concern for medical practitioners. P-glycoprotein (P-gp) overexpression is one of the major reasons for multidrug resistance in cancer chemotherapy. The P-gp overexpression in cancer cells depends on several factors like adenosine triphosphate (ATP) hydrolysis, hypoxia-inducible factor 1 alpha (HIF-1α), and drug physicochemical properties such as lipophilicity, molecular weight, and molecular size. Further multiple exposures of anticancer drugs to the P-gp efflux protein cause acquired P-gp overexpression. Unique structural and functional characteristics of nanotechnology-based drug delivery systems provide opportunities to circumvent P-gp mediated MDR. The primary mechanism behind the nanocarrier systems in P-gp inhibition includes: bypassing or inhibiting the P-gp efflux pump to combat MDR. In this review, we discuss the role of P-gp in MDR and highlight the recent progress in different nanocarriers to overcome P-gp mediated MDR in terms of their limitations and potentials.

How does CBCT reconstruction algorithm impact on deformably mapped targets and accumulated dose distributions?

PURPOSE: We performed quantitative analysis of differences in deformable image registration (DIR) and deformable dose accumulation (DDA) computed on CBCT datasets reconstructed using the standard (Feldkamp-Davis-Kress: FDK_CBCT) and a novel iterative (iterative_CBCT) CBCT reconstruction algorithms. METHODS: Both FDK_CBCT and iterative_CBCT images were reconstructed for 323 fractions of treatment for 10 prostate cancer patients. Planning CT images were deformably registered to each CBCT image data set. After daily dose distributions were computed, they were mapped to planning CT to obtain deformed doses. Dosimetric and image registration results based CBCT images reconstructed by two algorithms were compared at three levels: (A) voxel doses over entire dose calculation volume, (B) clinical constraint results on targets and sensitive structures, and (C) contours propagated to CBCT images using DIR results based on three algorithms (SmartAdapt, Velocity, and Elastix) were compared with manually delineated contours as ground truth. RESULTS: (A) Average daily dose differences and average normalized DDA differences between FDK_CBCT and iterative_CBCT were ≤1 cGy. Maximum daily point dose differences increased from 0.22 ± 0.06 Gy (before the deformable dose mapping operation) to 1.33 ± 0.38 Gy after the deformable dose mapping. Maximum differences of normalized DDA per fraction were up to 0.80 Gy (0.42 ± 0.19 Gy). (B) Differences in target minimum doses were up to 8.31 Gy (-0.62 ± 4.60 Gy) and differences in critical structure doses were 0.70 ± 1.49 Gy. (C) For mapped prostate contours based on iterative_CBCT (relative to standard FDK_CBCT), dice similarity coefficient increased by 0.10 ± 0.09 (p < 0.0001), mass center distances decreased by 2.5 ± 3.0 mm (p < 0.00005), and Hausdorff distances decreased by 3.3 ± 4.4 mm (p < 0.00015). CONCLUSIONS: The new iterative CBCT reconstruction algorithm leads to different mapped volumes of interest, deformed and cumulative doses than results based on conventional FDK_CBCT.

Recent Advancement in Nanotechnology-Based Drug Delivery System Against Viral Infections.

In the last few decades, the exponential rise in the incidence of viral infections sets a global health emergency across the world. The biomimetic architecture, the ability to hijack host immune responses, continuous antigen shifting, and drafting are the major critical factors that are responsible for the unavailability of a concrete therapeutic regimen against viral infections. Further, inappropriate pharmacodynamic physicochemical and biological parameters such as low aqueous solubility, poor permeability, high affinity for plasm proteins, short biological half-lives, and fast elimination from the systemic circulation are the major critical factors that govern the suboptimal drug concentration at the target site that leads to the development of drug resistance. To address this issue, nanotechnology-based drug delivery approach is emerged as an altering method to attain the optimal drug concentration at the target site for a prolonged period by integrating the nanoengineering tools in the synthesis of nanoparticles. Nanodimensional configuration with enhanced permeability and retention effect, increased surface-area-to-volume ratio, provision for surface functionalization, etc., are the privileged aspects that make it an effective drug delivery system for dispensing the antiviral therapeutics. However, size, shape, charge, and surface topology of nanoparticles are the greater influential factors that determine target-specific drug delivery, optimum cellular uptake, degree of opsonization by the host immune cells, drug retention time, transcytosis, the extension of biological half-life, in vivo stability, and cytotoxicity. The review will enlighten the elaborative role of nanotechnology-based drug delivery and the major challenging aspect of clinical safety and efficacy.

Recent Advancement in Topical Nanocarriers for the Treatment of Psoriasis.

Psoriasis is a life-threatening autoimmune inflammatory skin disease, triggered by T lymphocyte. Recently, the drugs most commonly used for the treatment of psoriasis include methotrexate (MTX), cyclosporine (CsA), acitretin, dexamethasone, and salicylic acid. However, conventional formulations due to poor absorptive capacity, inconsistent drug release characteristics, poor capability of selective targeting, poor retention of drug molecules in target tissue, and unintended skin reactions restrict the clinical efficacy of drugs. Advances in topical nanocarriers allow the development of prominent drug delivery platforms can be employed to address the critical issues associated with conventional formulations. Advances in nanocarriers design, nano-dimensional configuration, and surface functionalization allow formulation scientists to develop formulations for a more effective treatment of psoriasis. Moreover, interventions in the size distribution, shape, agglomeration/aggregation potential, and surface chemistry are the significant aspects need to be critically evaluated for better therapeutic results. This review attempted to explore the opportunities and challenges of current revelations in the nano carrier-based topical drug delivery approach used for the treatment of psoriasis.

Mucoadhesive formulations: innovations, merits, drawbacks, and future outlook.

Mucosa has now been recognized as a potential site for both local and systemic delivery of therapeutics. Mucoadhesive drug delivery systems with customizable release profiles have recently gained considerable interest among formulation scientists to improve clinical outcomes of drugs. This review summarizes the current development in the processing methods and polymers involved in mucoadhesive drug delivery systems. Mucoadhesive drug delivery systems are suitable for drugs that have a localized effect, undergo extensive pre-systemic metabolism, narrow absorption window, and narrow therapeutic index. Polymer characteristics like surface charge, hydrophilic surface groups, wettability, molecular weight, chain flexibility, molecular conformations, etc. are critical for assessing the extent of mucoadhesiveness and treatment response. The current review focuses on valuable principles, merits, drawbacks, and future outlooks of different mucoadhesive drug delivery systems.

Topical application of nanoparticles integrated supramolecular hydrogels for the potential treatment of seborrhoeic dermatitis.

The current application was aimed to evaluate the therapeutic potential of selenium and ketoconazole nanoparticles loaded hyaluronic acid gel against seborrhoeic dermatitis (SD). Amalgamation of ketoconazole (antifungal medication) and selenium (pro-oxidant) in an optimized formulation setting may help in the treatment of SD. In this study, selenium and ketoconazole nanoparticles loaded hyaluronic acid (HA) hydrogel was prepared by mechanical mixing followed by sonication. Results of the optimized batch showed a mean particle size of 121 ± 12 nm for ketoconazole and 51 ± 7 nm for selenium. SEM and TEM study revealed the prepared nanoparticles are of nanoscale dimension, with smooth spherical outline. Finally, the optimized nanoparticles were incorporated into HA hydrogel. Hydrogel exhibits desirable physical, mechanical and rheological characteristics appropriate for topical application. Optimized gel formulation exhibited an enhanced permeability with better antifungal, and anti-inflammatory activities, compared with the plain drug suspension. The optimized hydrogel with ketoconazole and selenium in nanotemplate could offer a potential strategy for the treatment of SD.

Improvement in severe lower respiratory symptoms and small airway function in World Trade Center dust exposed community members.

OBJECTIVE: Longitudinal assessment of lower respiratory symptoms (LRS) in community members with World Trade Center (WTC) exposures. METHODS: Adult members of a treatment program with complete standardized visits were evaluated (n = 798). Association of demographic characteristics, mental health symptoms and lung function with trajectory of LRS between initial and monitoring visit was evaluated. RESULTS: Severe LRS were present in 70% at initial and 63% at monitoring visit. Initial severe LRS were associated with WTC dust cloud exposure and mental health symptoms. Spirometry measures were not associated with LRS severity or trajectory; improvement in LRS was associated with improved lung function measured with forced oscillometry techniques. CONCLUSION: Many community patients in a WTC treatment program had severe LRS associated with exposures and mental health symptoms. Improvement in LRS was associated with improvement in measures of small airway function. Am. J. Ind. Med. 59:777-787, 2016. © 2016 Wiley Periodicals, Inc.

Prevention of ion migration in lead halide perovskites upon plugging the anion vacancies with PbSe islands.

To circumvent the issue of halide ion exchange in perovskites, we have decorated CsPbBr3 and CsPbI3 nanocrystals with different sized PbSe nanoparticles and demonstrated that it effectively prevents anion exchange reaction in CsPbBr3/CsPbI3 nanoheterostructures (NHSs) as a consequence of halide vacancy passivation by the more covalent selenide anion.

Identification of starvation-mimetic bioactive phytocomponent from Withania somnifera using in-silico molecular modelling and flow cytometry-based analysis for the management of malaria.

Multidrug resistance episodes in malaria increased from 3.9% to 20% from 2015 to 2019. Synchronizing the clinical manifestation in chronological sequence led to a unique impression on glucose demand (increased up to 100-fold) by the parasite-infected RBCs. Hence, restriction in the glucose uptake to parasite-infected RBCs could be an alternative approach to conquer the global burden of malaria to a greater extent. A C28 steroidal lactone Withaferin A (WS-3) isolated from Withania somnifera leave extract shows better thermodynamically stable interactions with the glucose transporters (GLUT-1 and PfHT) to standard drugs metformin and lopinavir. MD simulations for a trajectory period of 100 ns reflect stable interactions with the interactive amino acid residues such as Pro141, Gln161, Gln282, Gln283, Trp388, Phe389, and Phe40, Asn48, Phe85, His168, Gln169, Asn311 which potentiating inhibitory activity of WS-3 against GLUT-1 and PfHT respectively. WS-3 was non-hemotoxic (%hemolysis <5%) for a high concentration of up to 1 mg/ml in the physiological milieu. However, the %hemolysis significantly increased up to 30.55 ± 0.929% in a parasitophorous simulated environment (pH 5.0). Increased hemolysis of WS-3 could be due to the production of ROS in an acidic environment. Further, the inhibitory activity of WS-3 against both glucose transporters was supported with flow cytometry-based analysis of parasite-infected RBCs. Results show that WS-3 has low mean fluorescence intensities for both target proteins compared to conventional drugs, suggesting a potential sugar transporter inhibitor against GLUT-1 and PfHT for managing malaria. Communicated by Ramaswamy H. Sarma.

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.

Development, characterization, and evaluation of withaferin-A and artesunate-loaded pH-responsive acetal-dextran polymeric nanoparticles for the management of malaria.

Artemisinin and its derivatives have been commonly used to treat malaria. However, the emergence of resistance against artemisinin derivatives has posed a critical challenge in malaria management. In the present study, we have proposed a combinatorial approach, utilizing pH-responsive acetal-dextran nanoparticles (Ac-Dex NPs) as carriers for the delivery of withaferin-A (WS-3) and artesunate (Art) to improve treatment efficacy of malaria. The optimized WS-3 and Art Ac-Dex NPs demonstrated enhanced pH-responsive release profiles under parasitophorous mimetic conditions (pH 5.5). Computational molecular modeling reveals that Ac-Dex's polymeric backbone strongly interacts with merozoite surface protein-1 (MSP-1), preventing erythrocyte invasion. In-vitro antimalarial activity of drug-loaded Ac-Dex NPs reveals a 1-1.5-fold reduction in IC50 values compared to pure drug against the 3D7 strain of Plasmodium falciparum. Treatment with WS-3 Ac-Dex NPs (100 mg/kg) and Art Ac-Dex NPs (30 mg/kg) to Plasmodium berghei-infected mice resulted in 78.11 % and 100 % inhibition of parasitemia. Notably, the combination therapy comprised of Art and WS-3 Ac-Dex NPs achieved complete inhibition of parasitemia even at a half dose of Art, indicating the synergistic potential of the combinations. However, further investigations are necessary to confirm the safety and effectiveness of WS-3 and Art Ac-Dex NPs for their successful clinical implications.

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.