donepezil (E 2022 / TK023 / TK 023)

Comment on "Nano-enabled targeted transdermal therapy for pain management in cervical cancer".

Kamble Shubham S, Gurunani Gulshan G, Bodhankar Mitali M

Response to the Letter Regarding "Nano-enabled Targeted Transdermal Therapy for Pain Management in Cervical Cancer".

Odei-Mensah Beatrice B, Adeyemi Samson A SA, Choonara Yahya Essop YE

Rational design and synthesis of dispiroindene-pyrrolidinedione scaffolds as multi-target directed ligands: potent AChE inhibitors with antioxidant activity and favorable biocompatibility in SH-SY5Y cells.

Morsy Nagy A NA, El-Shiekh Riham A RA, Ebrahium Mohamad M MM, Srour Aladdin M AM

Addressing the urgent need for multi-target therapies in Alzheimer's disease, we report the rational design and one-pot, multi-component synthesis of novel substituted dispiroindene-pyrrolidinedione scaffolds (4a-r). Systematic biological evaluation identified five lead compounds (4g, 4j, 4k, 4m, and 4p) with potent inhibitory activity. Derivative 4k emerged as the primary lead, exhibiting an IC50 for Acetylcholinesterase (AChE) of 2.58 ± 0.11 μM and a remarkable selectivity index of 15.71, significantly exceeding that of donepezil (4.37), the reference drug. Concurrently, the series demonstrated notable affinity for Butyrylcholinesterase (BChE), with several derivatives exhibiting submicromolar to low micromolar inhibition. Furthermore, these scaffolds demonstrated superior antioxidant potential; notably, compound 4p achieved an IC50 value of 25.23 ± 1.25 μM, demonstrating an approximate 5-fold increase in radical scavenging potency relative to ascorbic acid (128.20 μM). In vitro safety assays on SH-SY5Y human neuroblastoma cells confirmed excellent biocompatibility, with compound 4m displaying an IC50 of 125.00 ± 6.91 μM, nearly four times less toxic than donepezil (32.84 μM). Molecular docking validated these results, showing robust π-π stacking and halogen-based stabilization within the catalytic anionic site. These findings, supported by ADME profiles predicting high blood-brain barrier permeability, position the dispiroindene-pyrrolidinedione framework as a highly effective, low-toxicity, multi-functional candidate for the development of Alzheimer's disease therapeutics.

Quality-by-design-steered development of nanoemulsion-enabled dissolving microneedle patch for enhanced berberine delivery in chronic wound healing.

Zaidi Syed Amir Azam SAA, Ali Asad A, Sultana Niha N, Emad Nasr A NA et al.

Berberine (BBR) has strong antibacterial, anti-inflammatory, and wound healing effects; its efficacy is limited by poor bioavailability and low skin permeability. In this study, a nano-dressing was developed by incorporating BBR-loaded nanoemulsion (BBR-NE) into a dissolvable microneedle patch to enhance drug delivery to the wound site. The BBR-NE was formulated via the aqueous titration method and optimized using the Box-Behnken design. The optimized formulation exhibited a globule size of 97.89 ± 0.4 nm, PDI 0.277 ± 0.035, and zeta potential of -30.99 ± 0.84 mV. In vitro drug release showed a biphasic pattern, with more than 75% drug released within 24 h, while ex vivo skin permeation demonstrated nearly twofold higher skin penetration compared to suspension, which was further confirmed by CLSM analysis. Additionally, the formulation also showed enhanced antibacterial activity against both Gram-positive and Gram-negative bacteria. The optimized formulation was further incorporated into a dissolvable microneedle patch (Opt-BBR-NE-MN) via a micro-molding technique. The in-vivo evaluation demonstrated that Opt-BBR-NE-MN was non-irritant and significantly accelerated healing in STZ-induced diabetic Wistar rats compared to the control groups. This nanodressing strategy overcomes delivery barriers and improves therapeutic outcomes in chronic wound care, underscoring its clinical potential.