Exploring the therapeutic potential of silymarin-based herbal remedy (prebiotic) and probiotic blend in a mouse model of NAFLD: Insights into gut microbiota modulation and liver health.

Non-alcoholic fatty liver disease (NAFLD) is a significant consequence of metabolic dysfunction, often associated with changes in the intestinal microbiota. Prebiotics and probiotics have shown promise in NAFLD management. This study evaluated a silymarin-based herbal remedy with piperine and fulvic acid, alongside a probiotic blend of Bifidobacterium adolescentis, Bifidobacterium bifidum, Lactobacillus casei, and Lactobacillus rhamnosus. Using a NAFLD mouse model induced by a high-fat and high-fructose diet, we assessed biochemical parameters, liver function, glucose levels, and conducted histological analysis. Stool samples underwent 16S rRNA metagenomic analysis to explore changes in microbiota composition. Mice on the high-fat diet exhibited elevated lipids, liver enzymes, and glucose, with reduced high-density lipoprotein levels (with p value < 0.001). Treatment, particularly with F3 (silymarin-piperine-fulvic acid herbal remedy and probiotic blend), significantly reduced hepatic fat accumulation and improved gut microbiota composition. This study highlights the potential of silymarin-based therapy combined with probiotics in attenuating NAFLD progression.

Synergistically engineered nanotransethosomes for co-delivery of methotrexate and baicalin for enhanced transdermal delivery against rheumatoid arthritis: formulation, characterisation and in vivo pharmacodynamic evaluation.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease that significantly impacts the quality of life of those affected. Owing to the complex pathophysiology of RA, it is not possible for any singular treatment to entirely impede the progression of the disease. Hence, the current study aimed to adopt a holistic and synergistic approach towards the management of RA by means of a co-delivery strategy involving methotrexate (MTH), a conventional slow-acting anti-rheumatic drug, and baicalin (BCN), a bioactive phytochemical using a transethosomal (TRS) gel formulation.Purpose: The present study aims to evaluate the potential benefits of administering MTH and BCN in nanoparticulate form, which may lead to improved stability and solubility, as well as enhanced penetration into the arthritic tissues of interest.Methods and results: The MTH-BCN-TRS that were synthesised exhibited small particle size of 151.3 nm and polydispersity index of 0.125, as well as a favourable zeta potential of -32.22 mV. Additional assessments were conducted, including a pharmacokinetic analysis, TEM, skin permeation analysis and confocal microscopy. According to the Confocal laser scanning microscopy (CLSM) study, the formulated MTH-BCN-TRS gel exhibited superior MTH and BCN permeation through the skin layers when compared to the MTH-BCN suspension gel. The MTT experiment on Raw 264.7 and SW982 cell lines revealed a considerable reduction (p < .05) in the IC50 value of the MTH-BCN-TRS formulation (9.2 mM and 43.2 mM, respectively) in comparison to the drug suspension. According to the findings of the in vivo study, it was found that the MTH-BCN-TRS gel exhibits significantly promising anti-arthritic properties when compared to the conventional diclofenac gel. This was demonstrated through histopathological studies and radiographic analysis. Furthermore, skin irritation investigation on Wistar albino rats confirmed that the formulated MTH-BCN-TRS is a safe option for topical treatment on the skin. The present study has confirmed that the formulated TRS vesicles are a valuable carrier for the transdermal delivery of MTH and BCN, which may be used for the management of rheumatoid arthritis.

Nose to brain delivery of naringin loaded transniosomes for epilepsy: formulation, characterisation, blood-brain distribution and invivo pharmacodynamic evaluation.

The current work limns the preparation of naringin-loaded transnioosomes (NRN-TN) to enhance NRN solubility, permeation and bioavailability via nasal mucosa for intranasal delivery. NRN-TN was created by the thin-film hydration technique, and with the BBD (Box-Behnken design), optimisation was carried out. NRN-TNopt was characterised for the vesicle size, PDI (Polydispersity index), zeta potential, entrapment efficiency (EE) and in vitro NRN release. For further assessment, nasal permeation study, study of Blood-brain distribution, TEM (Transmission Electron Microscopy), and CLSM (Confocal Scanning Laser Microscopy) were conducted withal. The NRN-TNopt exhibited spherical as well as sealed vesicles with a considerable small size of 151.3 nm, an EE of 75.23 percent, a PDI of 0.1257, and an in vitro release of 83.32 percent. CLSM investigation revealed that the new formulation allows for higher NRN permeation across nasal mucosa than the NRN solution. The blood-brain distribution investigation revealed that intranasally administered NRN-TN had a greater Cmax and AUC0-24 h than orally administered NRN-TN. Seizure activity and neuromuscular coordination as measured by the rotarod test, biochemical estimate of oxidative stress indicators, and histological investigations demonstrated that the NRN-TN has superior anti-epileptic potential in comparison to the standard diazepam. In addition, nasal toxicity studies demonstrate that the NRN-TN formulation is safer for intranasal administration. This study confirmed that the created TN vesicle formulation is a valuable carrier for the intranasal administration of NRN for the treatment of epilepsy.

Raloxifene encapsulated spanlastic nanogel for the prevention of bone fracture risk via transdermal administration: Pharmacokinetic and efficacy study in animal model.

This research work is to evaluate spanlastic-loaded raloxifene (RLX) nanogel administration via the transdermal route to avoid its hepatic metabolism and to enhance the bioavailability for better management of osteoporosis. RLX-loaded spanlastic nanogel was prepared and characterized for its viscosity, pH, spreadability, and texture profile. The formulation was applied on the skin surface of the animal for pharmacokinetic evaluation, and later, the efficacy of the formulation was assessed in ovariectomized female Wistar rats. The nanogel was obtained with a viscosity (2552.66 ± 30.61 cP), pH (7.1 ± 0.1), and spreadability (7.1 ± 0.2 cm). The texture properties, cohesiveness, and adhesiveness of the nanogel showed its suitability for transdermal application. Nanogel showed no sign of edema and erythema in the skin irritation test which revealed its safety for transdermal application. The t1/2 obtained for RLX-spanlastic nanogel (37.02 ± 0.59 h) was much higher than that obtained for RLX-oral suspension (14.43 h). The relative bioavailability was found to be 215.96% for RLX-spanlastic nanogel, and the drug and formulation did not show any toxicity in any of the vital organs, as well as no hematological changes occurring in blood samples. In microarchitectural measurement, RLX-spanlastic nanogel exhibited no unambiguous deviations along with improved bone mineral density compared to the RLX suspension treated group. Transdermal administration of RLX-spanlastic nanogel showed significant improvement of drug bioavailability (approx. twice to oral administration) without any toxic effect in the treated rats. Hence, spanlastic nanogel could be a better approach to deliver RLX via transdermal route for the management of osteoporosis.

Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB).

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies.

Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose, improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of -20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC0-24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.

Quality by Design-Optimized Glycerosome-Enabled Nanosunscreen Gel of Rutin Hydrate.

Sunburn is caused by prolonged exposure to ultraviolet (UV) rays from the sun, resulting in redness of the skin as well as tenderness, swelling, and blistering issues. During the healing process, it can cause peeling, irritation, and some long-term effects, including premature aging, pigmentation, and a high risk of skin cancer. Rutin has antioxidant and anti-inflammatory effects, which could potentially reduce inflammation and soothe sunburned skin. The objective of the current proposal is to develop and create carbopol gel-encased glycerosomes for the treatment of sunburn. The Design of Expert (DoE) technique was used to optimize the proposed formulation and was subjected to various characterization parameters such as nanovesicles size, polydispersity index (PDI), surface charge, entrapment efficiency (EE), and surface morphology. The optimized rutin-loaded glycerosomes (opt-RUT-loaded-GMs) were further characterised for drug release, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, and confocal laser scanning microscopy (CLSM). The formulation showed sustained release, greater permeation into the skin, and good antioxidant activity. The dermatokinetic study of opt-RUT-loaded-GMs confirms that the Rutin hydrate had better retention in the epidermis as compared to the dermis, owing to its potential for long lasting protection after topical application. It was observed that the prepared formulation was stable, highly safe, and had good sun protection factor (SPF) values that could be used as a suitable option for topical drug administration to maximize the therapeutic efficacy of the drugs.

Dissolving microneedle transdermal patch loaded with Risedronate sodium and Ursolic acid bipartite nanotransfersomes to combat osteoporosis: Optimization, characterization, in vitro and ex vivo assessment.

Osteoporosis is a fatal bone-wearing malady and a substantial reason behind the impermanence of human life and economic burden. Risedronate Sodium along with Ursolic acid has been studied to ameliorate osteoporosis. To bypass problems associated with bioavailability, we have developed a microneedle transdermal patch loaded with optimized formulation nanotransfersomes. It was optimized using three factor, three-level Central composite design with independent variables namely, the concentration of phospholipid, surfactant, and sonication time on dependent variables (vesicle size, entrapment efficiency and Polydispersity index). Vesicles of size 271.9 ± 8.45 nm with PDI 0.184 ± 0.01, having entrapment efficiency of 86.12 ± 5.20% and 85.65 ± 4.88% for RIS and UA respectively were observed. In vitro release study showed the sustained release pattern with 78.16 ± 1.12% and 75.72 ± 1.01% release of RIS and UA respectively. Dissolving MN patch prepared from gelatin was found to have good strength and folding endurance with uniform drug content (98.68 ± 0.004%). Ex vivo permeation study revealed that up to 80% of the drug can be permeated within 24 h. CLSM analysis was also performed to show penetration of RU-NTRs. From the results obtained, we can conclude that dissolving MN patch loaded with RU-NTRs has great potential than its conventional counterpart.

Lipid-based nanoparticle-mediated combination therapy for breast cancer management: a comprehensive review.

Breast cancer due to the unpredictable and complex etiopathology combined with the non-availability of any effective drug treatment has become the major root of concern for oncologists globally. The number of women affected by the said disease state is increasing at an alarming rate attributed to environmental and lifestyle changes indicating at the exploration of a novel treatment strategy that can eradicate this aggressive disease. So far, it is treated by promising nanomedicine monotherapy; however, according to the numerous studies conducted, the inadequacy of these nano monotherapies in terms of elevated toxicity and resistance has been reported. This review, therefore, puts forth a new multimodal strategic approach to lipid-based nanoparticle-mediated combination drug delivery in breast cancer, emphasizing the recent advancements. A basic overview about the combination therapy and its index is firstly given. Then, the various nano-based combinations of chemotherapeutics involving the combination delivery of synthetic and herbal agents are discussed along with their examples. Further, the recent exploration of chemotherapeutics co-delivery with small interfering RNA (siRNA) agents has also been explained herein. Finally, a section providing a brief description of the delivery of chemotherapeutic agents with monoclonal antibodies (mAbs) has been presented. From this review, we aim to provide the researchers with deep insight into the novel and much more effective combinational lipid-based nanoparticle-mediated nanomedicines tailored specifically for breast cancer treatment resulting in synergism, enhanced antitumor efficacy, and low toxic effects, subsequently overcoming the hurdles associated with conventional chemotherapy.

Linalool-Incorporated Synergistically Engineered Modified Liposomal Nanocarriers for Enhanced Transungual Delivery of Terbinafine against Onychomycosis.

This work investigates the synthesis of linalool-containing invasomes for terbinafine (TBF-IN) in order to increase the solubility, bioavailability, and nail permeability of terbinafine (TBF) for transungual administration. TBF-IN was created utilising the thin-film hydration technique, and with the Box-Behnken design (BBD), optimisation was carried out. TBF-INopt were investigated for vesicle size, zeta potential, PDI (Polydispersity index), entrapment efficiency (EE) and in vitro TBF release. In addition, nail permeation analysis, TEM (transmission electron microscopy), and CLSM (confocal scanning laser microscopy) were performed for further evaluation. The TBF-INopt exhibited spherical as well as sealed vesicles with a considerably small size of 146.3 nm, an EE of 74.23 per cent, a PDI of 0.1612, and an in vitro release of 85.32 per cent. The CLSM investigation revealed that the new formulation had better TBF nail penetration than the TBF suspension gel. The antifungal investigation demonstrated that the TBF-IN gel has superior antifungal activity against Trichophyton rubrum and Candida albicans compared to the commercially available terbinafine gel. In addition, an investigation of skin irritation using Wistar albino rats indicates that the TBF-IN formulation is safe for topical treatment. This study confirmed that the invasomal vesicle formulation is an effective vehicle for the transungual delivery of TBF for the treatment of onychomycosis.

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

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

Insights into Pharmacological Potential of Apigenin through Various Pathways on a Nanoplatform in Multitude of Diseases.

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.

Application of a Quality by Design-based approach in development and validation of an RP-HPLC method for simultaneous estimation of methotrexate and mangiferin in dual drug-loaded liposomes.

The present study delineates the development of a novel rugged and sensitive stability-indicating risk-based HPLC method for the concurrent estimation of methotrexate and mangiferin in dual drug-loaded nanopharmaceuticals based on an analytical QbD approach. Preliminary screening trials along with systemic risk analysis were performed, endeavouring to explicate the critical method attributes, namely pH, percentage orthophosphoric acid content and percentage methanol content, that influence critical quality attributes. Box-Behnken design was utilized for the optimization of the tailing factor as response for methotrexate and mangiferin in short run time. The chromatographic conditions were optimized by performing 17 experimental runs acquired from Design-Expert software. The chromatographic conditions after the analysis of an optimized zone within the confines of the design space were chosen as mobile phase water-methanol adjusted to pH 3.0 with 0.05% orthophosphoric acid (65:35, v/v) and flow rate 1.0 ml/min using a C18 analytical column at an isosbestic wavelength of 265 nm. Furthermore, the validation of the optimized method was done in accordance with International Conference on Harmonization guidelines and were reckoned to be in the prescribed limits. The developed RP-HPLC method has a high degree of practical utility for synchronous detection of methotrexate and mangiferin in pharmaceutical nano-dosage forms such as protein-based-nanoparticles, nanocrystals, polymeric nanoparticles and metallic nanoparticles in in vivo and in vitro studies.

Exploring new frontiers in drug delivery with minimally invasive microneedles: fabrication techniques, biomedical applications, and regulatory aspects.

INTRODUCTION: Transdermal drug delivery is limited by the stratum corneum, inhibiting the therapeutic potential of the permeants. Microneedles (MNs) have opened new frontiers in transdermal drug delivery systems. These micro-sized needles offer painless and accentuated delivery of drugs even with high molecular weights. AREAS COVERED: The review embodies drug delivery strategies with MNs with a description of MN types and fabrication techniques using various materials. The application of MN is not limited to drug delivery, but it also encompasses in vaccine delivery, diagnosis, phlebotomy, and even in the cosmetic industry. The review also tabulates MN-based marketed formulations. In a nutshell, we aim to present a panoramic view of MNs, including the design, applications, and regulatory aspects of MN. EXPERT OPINION: With the availability of numerous materials at the disposal of pharmaceutical scientists; the MN-based drug delivery technology has offered significant interventions toward the management of chronic maladies, including cardiovascular disorders, diabetes, asthma, mental depression, etc. As happens with any new technology, there are concerns with MN also such as biocompatibility issues with the material used for the fabrication. Nevertheless, the pharmaceutical industry must strive for preparing harmless, efficient, and cost-effective MN-based delivery systems for wider acceptance and patient compliance.

Application of QbD-based approach to the development and validation of an RP-HPLC method for simultaneous estimation of pregabalin and naringin in dual-drug loaded liposomes.

The current work delineates the development of a novel, rugged and sensitive stability-indicating risk-based HPLC method based on an analytical quality-by-design (QbD) approach for the concurrent estimation of naringin and pregabalin in dual-drug-loaded nanopharmaceuticals. Preliminary screening trials were conducted, along with systemic risk analysis, in order to identify the critical method attributes, namely injection volume, pH and acetonitrile content, that influence critical quality attributes. The Box-Behnken design was used to optimize the tailing factor as a response to pregabalin and naringin in a short run time. The chromatographic conditions were improved by running 17 experimental runs generated by design expert software. After analysing the optimized zone within the confines of the design space, the following chromatographic conditions were chosen: mobile phase water-acetonitrile adjusted to pH 6.9 with phosphate buffer (80:20, %v/v), at flow rate of 1.0 ml/min using a C18 analytical column at an isobestic wavelength of 212 nm. Furthermore, the optimized method was validated in accordance with International Conference on Harmonization guidelines and was found to be within the prescribed limits. The developed RP-HPLC method has a high degree of practical utility in in vivo and in vitro studies for the synchronous detection of pregabalin and naringin in pharmaceutical nanodosage forms such as protein-based nanoparticles, nanocrystals, polymeric nanoparticles and metallic nanoparticles.

Natural Medicine a Promising Candidate in Combating Microbial Biofilm.

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

Spanlastics as a Potential Approach for Enhancing the Nose-To-Brain Delivery of Piperine: In Vitro Prospect and In Vivo Therapeutic Efficacy for the Management of Epilepsy.

The present study delineates the preparation of piperine-loaded spanlastics (PIP-SPL) to improve piperine (PIP) solubility, bioavailability, and permeation through nasal mucosa for intranasal delivery. PIP-SPL was formulated using the thin-film hydration method and optimization was performed using Box-Behnken design (BBD). PIP-SPL optimized formulation (PIP-SPLopt) was characterized for polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential, and in vitro PIP release. For further evaluation, blood-brain distribution study, transmission electron microscopy (TEM), nasal permeation study, and confocal scanning laser microscopy (CLSM) were performed withal. The PIP-SPLopt presented spherical and sealed shape vesicles with a small vesicle size of 152.4 nm, entrapment efficiency of 72.93%, PDI of 0.1118, and in vitro release of 82.32%. The CLSM study unveiled that the developed formulation has greater permeation of PIP across the nasal mucosa in comparison with the PIP suspension. The blood-brain distribution study demonstrated higher Cmax and AUC0-24h of PIP-SPL via the intranasal route in comparison to PIP-SPL via oral administration. The in vivo study revealed that the PIP-SPL has good antiepileptic potential in comparison with the standard diazepam, which was evinced by seizure activity, neuromuscular coordination by rotarod test, biochemical estimation of oxidative stress markers, and histopathological studies. Furthermore, nasal toxicity study confirm that the developed PIP-SPL formulation is safer for intranasal application. The current investigation corroborated that the prepared spanlastic vesicle formulation is a treasured carrier for the PIP intranasal delivery for the management of epilepsy.

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

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

Nanotransethosomes for enhanced transdermal delivery of mangiferin against rheumatoid arthritis: formulation, characterization, invivo pharmacokinetic and pharmacodynamic evaluation.

The present research study limns the preparation of MNF loaded transethosomes (MNF-TE) to improve MNF solubility, bioavailability and permeation through skin layers for transdermal delivery. MNF-TE was formulated using thin-film hydration method and optimization was done using Box-Behnken design (BBD). MNF-TEopt was characterized for Polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential and in vitro MNF release. For further evaluation, Pharmacokinetic study, Transmission electron microscopy (TEM), Skin permeation study and Confocal scanning laser microscopy (CLSM) were performed withal. The MNF-TEopt presented spherical and sealed shape vesicles with small vesicle size of 148.6 nm, entrapment efficiency of 74.23%, PDI of 0.1139 and in vitro release of 65.32%. The CLSM study unveiled that the developed formulation has greater permeation of MNF across the skin layers in comparison with the MNF suspension gel. The pharmacokinetic study demonstrated Cmax and AUC0-24 h of 6.94 ± 0.51 µg/ml and 43.92 ± 7.90 µg.h/ml via transdermal route in comparison to Cmax and AUC0-24 h of 3.74 ± 1.91 µg/ml and 22.96 ± 9.76 µg.h/ml presented by MNF-TE oral administration. The in vivo study revealed that the MNF-TE gel has good anti-arthritic potential in comparison with the standard diclofenac gel which was evinced by radiographic analysis and histopathological studies. Further, skin irritation study on Wistar albino rats confirm that the developed MNF-TE formulation is safer for skin application. The current investigation corroborated that the prepared TE vesicle formulation is a treasured carrier for the MNF transdermal delivery for the management of rheumatoid arthritis.

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

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