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 C_max and AUC_0-24 h of 6.94 ± 0.51 μg/ml and 43.92 ± 7.90 μg.h/ml via transdermal route in comparison to C_max and AUC_0-24 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.

Aggregation of Amyloid-β (Aβ) leads to the formation and deposition of neurofibrillary tangles and plaques which is the main pathological hallmark of Alzheimer’s disease (AD). The bioavailability of the drugs and their capability to cross the BBB plays a crucial role in the therapeutics of AD. The present study evaluates the Memantine Hydrochloride (MeHCl) and Tramiprosate (TMPS) loaded solid lipid nanoparticles (SLNs) for the clearance of Aβ on SHSY5Y cells in rat hippocampus. Molecular docking and in vitro Aβ fibrillation were used to ensure the binding of drugs to Aβ. The in vitro cell viability study showed that the M + T SLNs showed enhanced neuroprotection against SHSY5Y cells than the pure drugs (M + T PD) in presence of Aβ (80.35µM ± 0.455 µM) at a 3:1 molar ratio. The Box–Behnken Design (BBD) was employed to optimize the SLNs and the optimized M + T SLNs were further characterized by %drug entrapment efficiency (99.24 ± 3.24 of MeHCl and 89.99 ± 0.95 of TMPS), particle size (159.9 ± 0.569 nm), PDI (0.149 ± 0.08), Zeta potential (−6.4 ± 0.948 mV), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM) and in vitro drug release. The TEM & AFM analysis showed irregularly spherical morphology. In vitro release of SLNs was noted up to 48 h; whereas the pure drugs released completely within 3 hrs. M + T SLNs revealed an improved pharmacokinetic profile and a 4-fold increase in drug concentration in the brain when compared to the pure drug. Behavioral tests showed enhanced spatial memory and histological studies confirmed reduced Aβ plaques in rat hippocampus. Furthermore, the levels of Aβ decreased in AlCl₃-induced AD. Thus, all these noted results established that the M + T SLNs provide enhanced neuroprotective effects when compared to pure and individual drugs and can be a promising therapeutic strategy for the management of AD.

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 C_max and AUC_0–24h 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.

A label free electrochemical sensor based on pure titanium oxide and manganese (Mn)-doped titanium oxide (TiO₂) nanoparticles are fabricated and characterized for the sensitive detection of myoglobin (Mb) levels to analyze the cardiovascular infarction. Pristine and Mn-doped TiO₂ nanoparticles were synthesized via the sol-gel method and characterized in order to understand their structure, morphologies, composition and optical properties. The structural properties revealed that the pure- and doped-TiO₂ nanoparticles possess different TiO₂ planes. FTIR studies confirm the formation of metal oxide nanoparticles by exhibiting a well-defined peak in the range of 600–650 cm⁻¹. The values of the optical band gap, estimated from UV-Vis spectroscopy, are decreased for the Mn-doped TiO₂ nanoparticles. UV-Vis spectra in the presence of myoglobin (Mb) indicated interaction between the TiO₂ nanoparticles and myoglobin. The SPE electrodes were then fabricated by printing powder film over the working electrode and tested for label-free electrochemical detection of myoglobin (Mb) in the concentration range of 0–15 nM Mb. The fabricated electrochemical sensor exhibited a high sensitivity of 100.40 μA-cm^−2/nM with a lowest detection limit of 0.013 nM (0.22 ng/mL) and a response time of ≤10 ms for sample S3. An interference study with cyt-c and Human Serum Albumin (HSA) of the sensors show the selective response towards Mb in 1:1 mixture.

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.

Introduction: Rhein, a natural bioactive lipophilic compound with numerous pharmacological activities, faces limitations in clinical application due to poor aqueous solubility and low bioavailability. Thus, this study aimed to develop a rhein-loaded self-nano emulsifying drug delivery system (RL-SNEDDS) to improve solubility and bioavailability. Methods: The RL-SNEDDS was prepared by aqueous titration method with eucalyptus oil (oil phase), tween 80 (surfactant), and PEG 400 (co-surfactant) and optimization was performed by 3² factorial design. The optimized formulation was characterized for Fourier transform infrared spectroscopy, differential scanning calorimetry, powdered X-ray diffraction, and Field emission scanning electron microscopy. Further, the oral bioavailability study and brain tissue pharmacokinetics study were performed on Sprague-Dawley rats. Results: The optimized RL-SNEDDS had an average droplet size of 129.3 ± 1.57 nm, zeta potential of − 24.6 mV ± 0.34, % transmittance of 94.82 ± 0.61, and encapsulation efficiency of 98.86 ± 0.23. Furthermore, RL-SNEDDS was transformed into solid RL-SNEDDS (RS-SNEDDS) to increase stability. In vitro release of rhein from RS-SNEDDS showed prolonged release up to 24h with 99.03± 1.04% drug release. Differential scanning calorimetry and powdered X-ray diffraction analysis confirmed the reduction in drug crystallinity and supported the results of the dissolution study. Field emission scanning electron microscopy analysis revealed the smooth and spherical nanosized globule of SNEDDS. Moreover, the in vivo pharmacokinetic study showed a significantly higher (p ≤ 0.05) value of C_max and AUC_0-t of RS-SNEDDS (8 ± 0.930 μg/mL and 37.79 ± 2.01 μg/mL*hr) compared to free rhein suspension (1.96 ± 0.712 μg/mL and 7.32 ± 0.946 μg/mL*hr) which indicated the enhancement of bioavailability of RS-SNEDDS. We also examined the C_max and AUC_0-t of RS-SNEDDS in the brain and it was found to be 2.90 ± 0.171 μg/mL and 18.18 ± 1.68 μg/mL*hr respectively. Conclusion: This study concludes that the RS-SNEDDS improves brain tissue concentration and oral bioavailability, both of which increase therapeutic potential.