Manish Kumar Chourasia

This study addresses the formidable challenge presented by the blood−brain barrier (BBB) in the treatment of neurological diseases by introducing a biomimetic delivery system utilizing extracellular vesicles, which efficiently crosses the BBB without requiring additional targeting moieties. Inspired by the neurotrophic function of the astrocytes, specifically the release of growth factors like Glial-Derived Neurotrophic Factor (GDNF), we harnessed extracellular vesicles from primary astrocytes (ADE), naturally enriched with GDNF (26.18 ± 4.15 pcg/mL), and subsequently coated them onto mesoporous silica nanoparticles loaded with donepezil (DNP), a model drug to formulate ADE_MSN-DNP. The system proposed BBB permeation and cellular uptake, significantly reduced oxidative stress in a Caenorhabditis elegans model, and increased plasma half-life and brain distribution in C57BL/6 male mice (6−8 months old), as estimated through LC−MS/MS and optical live imaging using Coumarin-6 as a fluorescent probe. The enhanced targeting and efficacy are proposed to be primarily attributed to intact GDNF and the intrinsic homing ability of the extracellular vesicles that facilitate efficient delivery of DNP. These findings provide valuable insights into a neurovascular unit-derived extracellular vesicle system that not only targets the brain and crosses the BBB but also offers a forward-looking strategy for neuroprotection in the mitigation of other neurodegenerative diseases.

Berberine (BBR) and bromocriptine (BM) exhibit significant therapeutic potential for neurodegenerative diseases, including Parkinson's disease; however, their clinical application is limited by poor stability, rapid clearance, and lack of unified platform for simultaneous evaluation. This study developed and validated a simple, reliable, and economical RP–HPLC with diode‐array detection–based method for their simultaneous quantification, adhering to ICH and US FDA guidelines. The method demonstrated excellent selectivity, linearity, precision, accuracy, and reproducibility and was successfully translated into bioanalytical method for plasma analysis. Forced degradation studies validated the method's ability to indicate stability under acidic, alkaline, oxidative, and thermal stress conditions. Polydopamine (PDA) nanoparticles (NPs) were developed to co‐encapsulate BBR and BM, exhibiting favorable physicochemical characteristics, high drug loading, and sustained in vitro release following diffusion‐controlled kinetics. Overall, the validated analytical and bioanalytical method verified its versatility across formulation development, stability assessment, release kinetics, and pharmacokinetic studies, whereas the PDA NP system demonstrated sustained delivery and improved pharmacokinetic performance, supporting its potential for further preclinical and pharmacodynamic studies for various neurodegenerative diseases.

Extracellular vesicles, including exosomes, are naturally produced by various cell types both in vivo and in vitro. These nanovesicles, composed of a lipid

Carbon dots cross the blood–brain barrier, disrupt Aβ and tau aggregation, and mitigate oxidative stress, offering a multifunctional nanoplatform for Alzheimer's disease therapy.

Despite advances in breast cancer therapy, its metastasis, particularly to bone, remains a significant challenge. Chemotherapeutic treatment with doxorubicin (DOX) elevates the circulating levels of TGF-β, potentially exacerbating bone metastasis. Moreover, DOX possesses several limitations, such as cardiotoxicity, rapid clearance, and multidrug resistance. Combinatorial therapy utilizing a (transforming growth factor) TGF-β inhibitor along with DOX could substantially reduce the metastatic burden. Baicalein (BAC), a key flavonoid, inhibits the TGF-β signaling pathway, potentially decreasing the bone metastatic ability of DOX. However, BAC is limited by poor solubility, low bioavailability, and a short half-life. Despite these challenges, a low combination index at a molar weight ratio of 1:4 (DOX:BAC) confirmed the synergistic potential of the combination. To deliver the ratiometric dose of both drugs, a PEGylated liposomal formulation loaded with DOX and BAC was developed using the ethanol injection method and evaluated for its anticancer and antimetastatic potential. The particle size of 132.53 ± 1.42 nm with narrow polydispersity and a ζ potential of -26.83 ± 2.2 mV were obtained for the developed nanoliposomes. The ratiometric combination loaded within the liposomal delivery carrier exhibited maximum synergistic activity in the syngeneic 4T1 BALB/c mice tumor model when administered intravenously through the tail vein. Moreover, the liposomal delivery vehicle showed a higher binding affinity toward hydroxyapatite, demonstrating selective bone accumulation. The results indicated efficient targetability and retention at the tumor site, as confirmed by pharmacokinetic profiling. Furthermore, micro-CT analysis revealed the preservation of bone architecture and minimal skeletal damage in treated groups. There was a 4.5-fold increase in the percent bone volume/total volume after treatment with nanoliposomes. These results highlight the promising therapeutic potential of combinatorial DOX and BAC delivery in the treatment of breast cancer-induced bone metastasis.

Overcoming the blood–brain barrier for effective therapy in neurodegenerative diseases through multifunctional nanocarriers targeting oxidative stress, mitochondrial dysfunction, and neuroinflammation.