Ashok Kumar Janakiraman

Amyloid-beta plaques and neurofibrillary tangles promote neuronal dysfunction and cognitive loss, the hallmarks of Alzheimer's disease (AD), a serious global health concern. Current medications offer only symptomatic alleviation, emphasizing the critical need for disease-- modifying therapy. This study was performed using MeSH term search by using keywords, like “Alzheimer’s Disease”, “AD”, “Vaccines”, “Nanoformulations”, “Amyloid-Beta (Aβ) Vaccines”, “lecanemab”, “Tau protein Vaccines”, “AADvac1”, “Clinical trials”. The development of vaccines and methods based on nanotechnology is the primary focal point of this review, which explores immunotherapeutic approaches. Active and passive immunization are used in the development of AD vaccines to target tau and amyloid-beta pathology. While passive immunization involves the direct delivery of pre-formed antibodies, active immunization aims to stimulate the patient's own immune system to produce antibodies in response to the antigen. The necessity for effective drug delivery across the blood-brain barrier (BBB), safety issues, and inconsistent efficacy are some of the difficulties facing vaccine delivery strategies. Nanotechnology can overcome the drawbacks of traditional treatments by providing novel approaches for gene therapy, RNA-based interventions, and targeted medication administration. Immunization approaches offer multiple benefits, including regulated and targeted antigen release, as well as stabilizing the vaccine antigens. Therapeutic drugs can be delivered across the BBB, and genes linked to AD can be modulated by nanoparticles and liposomes that resemble exosomes. Current developments, including the incorporation of short Aβ epitopes, liposomal formulations, conformational mimotopes, and virus-- like particles (VLPs), have markedly enhanced vaccine tolerability. Effective AD treatments depend on combination medications, individualized approaches, and ongoing research into crossing the BBB and improving the safety and effectiveness of vaccines.

Polyphenols, a structurally diverse class of plant-derived phytoconstituents, possess potent antioxidant, anti-inflammatory, and vasoprotective properties that make them promising therapeutic candidates for ocular disorders driven by oxidative stress, chronic inflammation, and overall health. Despite this potential, their clinical translation remains restricted due to the inherent limitations of conventional ocular delivery systems, such as low ocular bioavailability, rapid precorneal elimination, poor corneal permeability, and inadequate targeting of posterior ocular tissues. To address these challenges, recent research has focused on advanced formulation approaches designed to enhance polyphenol retention, penetration, and sustained release within ocular tissues. These include nanoemulsions, polymeric micelles lipid and polymer-based nanocarriers, in situ gelling systems, mucoadhesive and stimuli-responsive platforms, and advanced drug delivery platforms for the posterior and anterior ocular segments. Mechanistically, these systems exploit physicochemical and biological strategies such as enhancing mucoadhesion, modulating paracellular transport, and leveraging endocytic uptake to improve drug disposition and therapeutic performance. The review critically examines these innovative formulation platforms, delineates their pharmacokinetic and pharmacodynamic outcomes, and discusses safety, manufacturing challenges, and regulatory considerations that presently influence their clinical progression. Overall, it highlights emerging formulation technologies most likely to facilitate the successful clinical translation of polyphenol-based ocular therapies.

Background: Oral fast-melting tablets (FMTs) have been gaining popularity due to their advantages in resolving swallowing issues of conventional oral tablets. Cocoa butter is an excipient of choice to develop FMT with an acceptable taste and faster onset of action of the drug. Purpose: The present study aimed to prepare and characterize the amlodipine besylate-loaded cocoa butter FMTs. Method: Amlodipine besylate FMTs were prepared using a simple freezing (refrigeration) method. Cocoa butter (Form V) was used as the base to achieve a final tablet weight of 500 mg with drug and other functional excipients. The designed prototype tablet formulations were subjected to disintegration tests to determine the robust selected batch. The formulation F4, containing 7% high-molecular-weight chitosan, exhibited the quickest disintegration time of 1.45 ± 0.10 min. Afterwards, the selected formulation, F4, was subjected to quality evaluation parameters. Results: Fourier transform infrared spectroscopy (FTIR) studies revealed that there was no incompatibility between amlodipine besylate, cocoa butter, and other excipients. The average hardness of the F4 formulation tablet batch was found to be 2.69 ± 0.21 kg/cm2 and a friability of less than 1%. The drug content in F4 tablets was found to be 102.38 ± 5.29% and showed an in-vitro drug release of 94.30 ± 2.63% within 30 min. Over a six-month stability testing period, the chosen F4 formulation did not significantly change in terms of tablet average weight, disintegration time, drug content, and in-vitro dissolution rate. Conclusions: Selected formulation F4 with 7% of high molecular weight chitosan exhibited good physical properties, indicating the suitability of cocoa butter as a base to produce FMTs with the aid of a natural super-disintegrant.

Colorectal cancer (CRC) remains a major health concern worldwide, with current treatments associated with significant side effects and resistance. Traditional Chinese medicine (TCM), particularly BuShenFang (BSF), has shown potential as an alternative therapeutic strategy. However, the exact mechanism of BSF's action in CRC treatment is not fully understood. Despite the promising anticancer properties of BSF, its mechanism in inhibiting colorectal tumor progression remains unclear, necessitating further investigation. This study aims to evaluate the inhibitory effects of BSF on intestinal adenoma development in APCmin/+ mice and elucidate its underlying mechanism, focusing on the Wnt/β-catenin signaling pathway. APCmin/+ mouse were randomly assigned into four groups: control, low-dose BSF (100 mg/kg), high-dose BSF (200 mg/kg), and xStAxVHLL (positive control). After 11 weeks of treatment, tumor burden, histopathological changes, cell proliferation, apoptosis, and key signaling proteins were assessed using HE staining, immunohistochemistry, TUNEL assay, and Western blot analysis. BSF treatment significantly reduced tumor count and size in a dose-dependent manner. High-dose BSF suppressed tumor cell proliferation, promoted apoptosis, and enhanced APC expression while inhibiting β-catenin accumulation and its downstream targets, including c-Myc, Cyclin D1, and COX-2. These findings suggest that BSF exerts its anti-tumor effects through modulation of the Wnt/β-catenin pathway. BSF demonstrates significant potential in inhibiting colorectal tumorigenesis via modulation of key oncogenic pathways. Further research is warranted to explore its clinical applications and optimize therapeutic dosing.

Colorectal cancer (CRC) remains a major global health burden, necessitating alternative therapeutic approaches. Traditional Chinese Medicine (TCM), including BuShenFang (BSF), has demonstrated potential anti-CRC effects, yet its precise mechanisms remain unclear. While BSF has previously exhibited anti-CRC activity in vitro, it’s in vivo efficacy and associated molecular mechanisms requires further elucidation. In this study, a subcutaneous xenograft model was established in nude mice, which lack T-cell-mediated immunity and can effectively support the growth of human colorectal cancer cells (HCT116). This model enables a more clinically relevant evaluation of BSF’s antitumor effects in vivo. The study aimed to assess the tumor inhibitory effect of BSF and investigate its underlying mechanisms via the Wnt/β-catenin signaling pathway. Mice were allocated into control, low-dose BSF (L-BSF), high-dose BSF (H-BSF), and xStAxVHLL (positive control) groups. Tumor growth was monitored, and analyses including histology, immunohistochemistry, TUNEL assay, immunofluorescence, and Western blotting were performed to examine tumor proliferation, apoptosis, and Wnt pathway regulation. BSF significantly inhibited tumor growth in a dose-dependent manner, reduced KI67 expression, promoted apoptosis, and increased adenomatous polyposis coli (APC) levels. Additionally, BSF downregulated β-catenin, p-GSK-3β/GSK-3β, and Axin1, while suppressing Wnt target genes (Cyclin D1, c-Myc, COX-2). The decrease in p-GSK-3β (Ser9) suggests increased GSK-3β activity, which promotes β-catenin degradation and attenuates Wnt/β-catenin signaling. These indicate that BSF inhibits CRC progression through modulation of the Wnt/β-catenin signaling pathway, promoting apoptosis and suppressing tumor proliferation. This highlights its potential as an adjunct therapy in CRC treatment. In conclusion, these findings suggest that BSF may exert anti-CRC effects by targeting key tumorigenic pathways in preclinical study. Further research, including clinical trials, is needed to confirm its therapeutic potential.

Intranasal drug delivery shows potential for brain access via olfactory and trigeminal routes. This work aimed to ensure brain availability of nalbuphine via the nasal route. Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised. SEM results revealed that the nanoparticles were spherical in shape, with an average size of 192.4 ± 11.6 nm. Zeta potential and entrapment efficiency was found 32.8 mV and 88.43 ± 7.75%, respectively. The X-ray diffractometry and DSC results unravel a profound understanding on the physical and thermal characteristics. The in-vitro release of nalbuphine from the nanoparticles was biphasic, with an initial burst release followed by a slow-release profile. In-vitro cell study on HEK-293 cells and microscopic images of brain tissue confirmed the safety profile of formulation. In-vivo efficacy studies on animal confirmed the effectiveness of developed intranasal formulation as compared to the standard therapy. The in-vivo pharmacokinetic studies showed that the prepared nanoparticles were able to efficiently deliver nalbuphine to the brain in comparison to the other body organs. Gamma scintigraphy images showed retention of the drug in the brain. Furthermore, the efficacy studies confirmed that the nanoparticles were found significantly more effective than the marketed formulation in pain management.