Auranofin-loaded PLGA nanoparticles alleviate cognitive deficit induced by streptozotocin in rats model: modulation of oxidative stress, neuroinflammatory markers, and neurotransmitters.

Alzheimer's disease remains an unsolved neurological puzzle with no cure. Current therapies offer only symptomatic relief, hindered by limited uptake through the blood-brain barrier. Auranofin, an FDA-approved compound, exhibits potent antioxidative and anti-inflammatory properties targeting brain disorders. Yet, its oral bioavailability challenge prompts the exploration of nanoformulation-based solutions enhancing blood-brain barrier penetrability. The study aimed to investigate the neuroprotective potential of auranofin nanoparticles in streptozotocin-induced AD rats. Auranofin-containing polylactic-co-glycolic acid nanoparticles were formulated by the multiple emulsion solvent evaporation method. Characterization was done by determining entrapment efficiency, particle size distribution, surface charge, and morphology. An in vivo study was performed by administering streptozotocin (3 mg/kg/i.c.v., days 1 and 3), auranofin (5 and 10 mg/kg), auranofin nanoparticles (2.5 and 5 mg/kg), and donepezil (2 mg/kg) for 14 days orally. Behavioral deficits were evaluated using the open field test, Morris water maze, objective recognition test, change in oxidative stress levels, and AD markers in the brain. Following the decapitation of the rats, the brains were excised to isolate the hippocampus. Subsequent analyses included the quantification of biochemical and neuroinflammatory markers, as well as the assessment of neurotransmitter levels. The characterization of auranofin nanoparticles showed an entrapment efficiency of 98%, an average particle size of 101.5 ± 10.3 nm, a surface charge of 27.5 ± 5.10 mV, and a polydispersity index of 0.438 ± 0.12. In vivo, administration of auranofin and auranofin nanoparticles significantly reversed streptozotocin-induced cognitive deficits, biochemical alteration, neuroinflammatory markers, and neurotransmitter levels. The present finding suggests that auranofin nanoparticles have more significant neuroprotective potential than auranofin alone. The therapeutic efficacy may be attributed to its antioxidant and anti-inflammatory properties, as well as its positive neuromodulatory effects. Therefore, our findings suggest that it could be a promising candidate for Alzheimer's disease therapy.

Monoclonal Antibodies: Current Advancements and Future Potential for Atopic Dermatitis Therapy.

BACKGROUND: Atopic Dermatitis (AD) is an inflammatory skin condition with a severe itch. The topical therapy using corticosteroids is not sufficient for the effective therapy of moderate to severe cases of AD. The investigation and development of immunological targetspecific human monoclonal antibodies have changed the paradigm for the therapy of moderate to severe cases of AD. OBJECTIVE: The establishment of target-specific, tolerable, and efficacious human monoclonal antibodies might lead to the better management of moderate to severe cases of AD. METHODOLOGY: The scientific literature available in databases, such as Pubmed and Clinicaltrial.gov, was searched and discussed for available clinical therapeutic information. DISCUSSION: The present review has discussed the potential immunological targets of specific monoclonal antibodies developed and approved or which are under investigation in clinical trials. CONCLUSION: The development of targeted monoclonal antibodies can improve the understanding of the role of different immunological pathways and biomarkers in AD and become the future of AD treatment.

Aurothioglucose encapsulated nanoparticles fostered neuroprotection in streptozotocin-induced Alzheimer's disease.

Alzherimer's disease (AD) is an age-dependent ubiquitous ailment worldwide with limited therapies that only alleviate the symptoms of AD but do not cure them entirely because of the restricted blood-brain barrier passage of the drug. Hence with new advanced technology, nanoparticles can offer an opportunity as the active candidate to overcome the above limitations. Aurothioglucose, a synthetic glucose derivative of the gold compound, has been clinically proven to be an effective anti-inflammatory drug for rheumatic arthritis. Recently, several scientific groups have developed gold nanoparticle preparations and tested them for the treatment of dementia. This study was planned to prepare the PLGA nanoparticles of aurothioglucose (ATG) and check the neuroprotective potential against STZ-induced AD in rats. The nanoparticles were prepared using the double emulsion solvent evaporation method and characterized for various parameters such as drug-excipient interaction, particle size, zeta potential, and morphology. Then, rats were injected STZ (3 mg/kg/i.c.v., days 1 and 3) and ATG (5 and 10 mg/kg/s.c.), ATG NPs (2.5 and 5 mg/kg/s.c.) and donepezil (2 mg/kg/p.o) from 15th to 29th day. Behavior parameters were performed using an actophotometer, MWM, and ORT. On the 30th day, all the animals were sacrificed, and the brains were isolated for estimating biochemical, neurochemical, and proinflammatory markers. It was observed that ATG NPs significantly restored all behavior and neurotransmitter alterations caused by STZ. Also, it increased antioxidant levels and decreased inflammatory cytokines significantly, then ATG alone. Thus, the study suggests that ATG loaded PLGA NPs could be used as a novel therapeutic strategy to slow the process of AD.

Recent Trends in Nanocarriers for the Management of Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a pruritic inflammatory skin condition with increasing global prevalence, almost affecting 15% to 30% of children and 5% of adults. AD results due to a complex interaction between the impaired skin barrier function, allergens, and immunological cells. Topical corticosteroids or calcineurin inhibitors in the form of creams or ointments are the mainstay of therapy, but they have low skin penetration and skin barrier repair efficiency. OBJECTIVE: The above limitations of conventional dosage forms have motivated the development of nanoformulations of drugs for improved penetration and deposition in the skin for better management of AD. METHODS: Databases, such as Pubmed, Elsevier, and Google Scholar, were reviewed for the investigations or reviews published related to the title. RESULTS: The present review discusses the advantages of nanoformulations for the management of AD. Further, it also discusses the various types of topically investigated nanoformulations, i.e., polymeric nanoparticles, inorganic nanoparticles, solid lipid nanoparticles, liposomes, ethosomes, transfersomes, cubosomes, and nanoemulsion for the management of atopic dermatitis. In addition, it also discusses advancements in nanoformulations, such as nanofibres, nanosponges, micelles, and nanoformulations embedded textiles development for the management of AD. CONCLUSION: The nanoformulations of drugs can be a better alternative for the topical management of AD with enhanced skin penetration and deposition of drugs with reduced systemic side effects and better patient compliance.

Potential Phytoconstituents of Genus Vitex for the Management of Rheumatoid Arthritis: A Review.

Rheumatoid arthritis is one of the most predominant conditions which have utmost influence on the society. The disease is an inflammatory disorder which affects joints, connective tissues, muscles, tendons and fibrous tissues. Approximately 270 known species of vitex genus are known, extending from shrubs to trees in the tropical, sub-tropical regions and temperate zones. Several species of vitex have been used traditionally over world-wide. The main focus of the present study is to review various phytoconstituents isolated from the genus vitex which can be used for the treatment of rheumatic disorders. The study also covers the underlying targets of the phytoconstituents which can be possible potential hits for the management of Rheumatic disorders.

Topical creams of piperine loaded lipid nanocarriers for management of atopic dermatitis: development, characterization, and in vivo investigation using BALB/c mice model.

The aim of the research work was to investigate the efficacy of cream loaded with lipid nanocarriers (ethosomes) of piperine for the management of atopic dermatitis (AD) in comparison to conventional cream. Ethosomes of piperine were formulated with varying concentration of phosphatidylcholine and ethanol; and evaluated for entrapment efficiency (EE), sedimentation behaviour, vesicle size, zeta potential, in vitro drug release, and shape. Creams loaded with optimized ethosomal dispersion of piperine were formulated and evaluated for physicochemical parameters, ex vivo permeation and drug retention in skin layers. Similarly, conventional creams of piperine in the same concentrations were formulated and evaluated. The optimized ethosomal a conventional cream was evaluated for cytotoxicity using HaCat cell lines and in vivo on BALB/c mice model. The EE (%) and vesicle size was 74.30 ± 3.88% and 318.1 nm, respectively, for optimized ethosomal dispersion. The zeta potential was -32.6 mV and vesicles were spherical in shape. The ethosomal cream showed higher deposition in the epidermis and dermis. The creams were non-cytotoxic to HaCat cell lines. In comparison to the negative control, the ethosomal (0.1%) and conventional (0.125%) cream, both significantly decreased the ear and skin thickness, skin severity; and WBC, granulocytes, and IgE antibodies level in the BALB/c mice model. The efficacy of ethosomal cream was significantly higher than conventional cream as compared to tacrolimus (0.1%). Ethosomal cream of piperine showed good potential for the management of AD in comparison to conventional cream.