Transdermal delivery of resveratrol loaded solid lipid nanoparticle as a microneedle patch: a novel approach for the treatment of Parkinson's disease.

Parkinson's disease (PD), affecting millions of people worldwide and expected to impact 10 million by 2030, manifests a spectrum of motor and non-motor symptoms linked to the decline of dopaminergic neurons. Current therapies manage PD symptoms but lack efficacy in slowing disease progression, emphasizing the urgency for more effective treatments. Resveratrol (RSV), recognized for its neuroprotective and antioxidative properties, encounters challenges in clinical use for PD due to limited bioavailability. Researchers have investigated lipid-based nanoformulations, specifically solid lipid nanoparticles (SLNs), to enhance RSV stability. Oral drug delivery via SLNs faces obstacles, prompting exploration into transdermal delivery using SLNs integrated with microneedles (MNs) for improved patient compliance. In this study, an RSV-loaded SLNs (RSV -SLNs) incorporated into the MN patch was developed for transdermal RSV delivery to improve its stability and patient compliance. Characterization studies demonstrated favorable physical properties of SLNs with a sustained drug release profile of 78.36 ± 0.74%. The developed MNs exhibited mechanical robustness and skin penetration capabilities. Ex vivo permeation studies displayed substantial drug permeation of 68.39 ± 1.4% through the skin. In an in vivo pharmacokinetic study, the RSV-SLNs delivered through MNs exhibited a significant increase in Cmax, Tmax, and AUC0 - t values, alongside a reduced elimination rate in blood plasma in contrast to the administration of pure RSV via MNs. Moreover, an in vivo study showcased enhanced behavioral functioning and increased brain antioxidant levels in the treated animals. In-vivo skin irritation study revealed no signs of irritation till 24 h which permits long-term MNs application. Histopathological analysis showed notable changes in the brain regions of the rat, specifically the striatum and substantia nigra, after the completion of the treatment. Based on these findings, the development of an RSV-SLN loaded MNs (RSVSNLMP) patch presents a novel approach, with the potential to enhance the drug's efficiency, patient compliance, and therapeutic outcomes for PD, offering a promising avenue for advanced PD therapy.

Enhancing selegiline hydrochloride efficacy: Box Behnken-optimized liposomal delivery via intranasal route for Parkinson's disease intervention.

The clinical use of selegiline hydrochloride in conventional dosage forms is to reduce the progression of Parkinson's disease (PD). However, its limited access to the brain, short half-life, and first-pass metabolism minimize brain uptake. Nano-based liposomes offer promising tools for brain-targeted delivery of therapeutics, especially intranasally administered cationic liposomes that target the brain region via the olfactory route and reduce biodistribution. In the present work, cationic liposomes encapsulated with selegiline hydrochloride were fabricated for intranasal administration against PD. The liposomes were initially optimized by Box Behnken design, and the selected run was coated with stearylamine to provide a cationic charge to the liposomes. The final coated liposomes, SH-LP3, demonstrated a minimum size of 173 ± 2.13 nm, an ideal zeta potential of +16 ± 1.98, and achieved a maximum entrapment efficiency of 40.14 ± 1.83%. Morphology analysis showed the spherical shape of liposomes in the size range of 100-200 nm. The in vitro cytotoxicity assay in SHSY5Y cell lines showed a significant decrease in toxicity, almost ten times less, compared to pure selegiline hydrochloride. Animal studies on rotenone-lesioned C57BL6 mice model for PD were performed to investigate the effect of intranasally administered liposomes. The SH-LP3 formulation exhibited remarkable effectiveness in relieving symptoms of PD. This extensive analysis emphasizes the possibility of intranasally administered SH-LP3 liposomes as a feasible treatment option for PD. The formulation not only delivers continuous drug release but also displays better safety and efficacy, providing a platform for additional studies and growth in the domain of PD treatment.

The use of cellulose, chitosan and hyaluronic acid in transdermal therapeutic management of obesity: A review.

Obesity is a clinical condition with rising popularity and detrimental impacts on human health. According to the World Health Organization, obesity is the sixth most common cause of death worldwide. It is challenging to combat obesity because medications that are successful in the clinical investigation have harmful side effects when administered orally. The conventional approaches for treating obesity primarily entail synthetic compounds and surgical techniques but possess severe adverse effects and recurrences. As a result, a safe and effective strategy to combat obesity must be initiated. Recent studies have shown that biological macromolecules of the carbohydrate class, such as cellulose, hyaluronic acid, and chitosan, can enhance the release and efficacy of medications for obesity but due to their short biological half-lives and poor oral bioavailability, their distribution rate is affected. This helps to comprehend the need for an effective therapeutic approach via a transdermal drug delivery system. This review focuses on the transdermal administration, utilizing cellulose, chitosan, and hyaluronic acid via microneedles, as it offers a promising solution to overcome existing therapy limitations in managing obesity and it also highlights how microneedles can effectively deliver therapeutic substances through the skin's outer layer, bypassing pain receptors and specifically targeting adipose tissue.

Current advancements related to phytobioactive compounds based liposomal delivery for neurodegenerative diseases.

Neurodegenerative diseases are the most widely affected disease condition in an aging population. The treatment available reduces the elevated manifestations but is ineffective due to the drug's poor bioavailability, plasma stability, and permeability across the blood-brain barrier (BBB). Until now, no therapeutic compound has been able to stop the progression of neurodegenerative disease. Even the available therapeutic moiety manages it with possible adverse effects up to the later stage. Hence, phytobioactive compounds of plant origin offer effective treatment strategies against neurodegenerative diseases. The only difficulty of these phytobioactive compounds is permeability across the BBB. Engineered nanocarriers such as liposomes provide high lipid permeability across BBB. Liposomes have unique physicochemical properties that are widely investigated for their application in diagnosing and treating neurodegenerative diseases. The surface modification on liposomes by peptides, antibodies, and RNA aptamers offers receptor targeting. These brain-targeted approaches by liposomes improve the efficacy of phytoconstituents. Additional surface modification methods are utilized on liposomes, which increases the brain-targeted delivery of phytobioactive compounds. The marketing strategy of the liposomal delivery system is in its peak mode, where it has the potential to modify the existing therapy. This review will summarize the brain target liposomal delivery of phytobioactive compounds as a novel disease-modifying agent for treating neurodegenerative diseases.

Microneedles: A versatile drug delivery carrier for phytobioactive compounds as a therapeutic modulator for targeting mitochondrial dysfunction in the management of neurodegenerative diseases.

Neurodegenerative disease (ND) is the fourth leading cause of death worldwide, with limited symptomatic therapies. Mitochondrial dysfunction is a major risk factor in the progression of ND and increases the generation of reactive oxygen species (ROS). Overexposure to these ROS induces apoptotic changes leading to neuronal cell death. Many studies have shown the prominent effect of phytobioactive compounds in managing mitochondrial dysfunctions associated with ND, mainly due to their antioxidant properties. Drug delivery to the brain is limited due to the presence of the blood-brain barrier (BBB), but effective drug concentration needs to reach the brain for the therapeutic action. Therefore, developing safe and effective strategies to enhance drug entry in the brain is required to establish ND's treatment. The microneedle-based drug delivery system is one of the effective non-invasive techniques for drug delivery through the transdermal route. Microneedles are micron-sized drug delivery needles that are self-administrable. They can penetrate through the stratum corneum skin layer without hitting pain receptors, allowing the phytobioactive compounds to be released directly into systemic circulation in a controlled manner. With all of the principles mentioned above, this review discusses microneedles as a versatile drug delivery carrier for phytobioactive compounds as a therapeutic potentiating agent for targeting mitochondrial dysfunction for the management of ND.

Chemopreventive Potential of Dietary Nanonutraceuticals for Prostate Cancer: An Extensive Review.

There are more than two hundred fifty different types of cancers, that are diagnosed around the world. Prostate cancer is one of the suspicious type of cancer spreading very fast around the world, it is reported that in 2018, 29430 patients died of prostate cancer in the United State of America (USA), and hence it is expected that one out of nine men diagnosed with this severe disease during their lives. Medical science has identified cancer at several stages and indicated genes mutations involved in the cancer cell progressions. Genetic implications have been studied extensively in cancer cell growth. So most efficacious drug for prostate cancer is highly required just like other severe diseases for men. So nutraceutical companies are playing major role to manage cancer disease by the recommendation of best natural products around the world, most of these natural products are isolated from plant and mushrooms because they contain several chemoprotective agents, which could reduce the chances of development of cancer and protect the cells for further progression. Some nutraceutical supplements might activate the cytotoxic chemotherapeutic effects by the mechanism of cell cycle arrest, cell differentiation procedures and changes in the redox states, but in other, it also elevate the levels of effectiveness of chemotherapeutic mechanism and in results, cancer cell becomes less reactive to chemotherapy. In this review, we have highlighted the prostate cancer and importance of nutraceuticals for the control and management of prostate cancer, and the significance of nutraceuticals to cancer patients during chemotherapy.