Polymer–drug conjugates as nano-sized multi-targeting systems for the treatment of Alzheimer's disease

Mahadik, Nuruddin; Barron, Gemma A.; Kong Thoo Lin, Paul; Thompson, Colin J.

doi:10.1039/d3pm00075c

RSC Pharm.

2024

DOI: 10.1039/d3pm00075c

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Polymer–drug conjugates as nano-sized multi-targeting systems for the treatment of Alzheimer's disease

Nuruddin Mahadik,

Gemma A. Barron,

Paul Kong Thoo Lin

et al.

Abstract: Alzheimer’s disease (AD) is a progressive, neurodegenerative condition. There are clear markers for the presence and progression of the disease, including β-amyloid (Aβ) plaques and Tau tangles, with many potential...

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2024

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Cited by 3 publications

References 117 publications

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Polymer–drug and polymer–protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications

Guo,

2024

WIREs Nanomed Nanobiotechnol

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Polymer–drug conjugates and polymer–protein conjugates have been pivotal in the realm of drug delivery systems for over half a century. These polymeric drugs are characterized by the conjugation of therapeutic molecules or functional moieties to polymers, enabling a range of benefits including extended circulation times, targeted delivery, controlled release, and decreased immunogenicity. This review delves into recent advancements and challenges in the clinical translations and preclinical studies of polymer–drug conjugates and polymer–protein conjugates. The design principles and functionalization strategies crucial for the development of these polymeric drugs were explored followed by the review of structural properties and characteristics of various polymer carriers. This review also identifies significant obstacles in the clinical translation of polymer–drug conjugates and provides insights into the directions for their future development.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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Polymer–drug and polymer–protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications

Guo,

2024

WIREs Nanomed Nanobiotechnol

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Hydroxyapatite–polymer nanocomposites for drug delivery applications: A mini review

Behmagham,

Dhiaa,

Hussein

et al. 2024

European Journal of Medicinal Chemistry Reports

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Synthesis and Evaluation of Polymer-Drug Conjugates as Potential Antioxidants and Cholinesterase Inhibitors for Neurodegenerative Diseases

Mahadik,

Barron,

Thoo Lin

et al. 2024

Chem. Mater.

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Polymer-drug conjugates (PDCs) may offer improved water-solubility and in vitro activity of potential antioxidant and cholinesterase (ChE) inhibitor drugs compared to the drugs alone. Conjugation of these potential drugs to water-soluble polymers could increase their therapeutic efficacy. Vanillin was conjugated to poly(allylamine hydrochloride) (NM10 and NM15) and naphthalimidohexylamine (HEXNAP) was conjugated to poly(acrylic acid) (N5 and N10). The antioxidant and cholinesterase inhibitory activities of these novel PDCs were evaluated and compared with those of their respective starting materials. Additionally, in silico molecular modeling studies were conducted to explore the potential cholinesterase inhibitory mechanisms of these conjugates. NM15 (unadjusted and adjusted value) showed significantly enhanced in vitro antioxidant activity (p ≤ 0.0001) compared to vanillin. The adjusted value of N5 compared to HEXNAP showed significantly enhanced in vitro cholinesterase inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) (p ≤ 0.0001). Kinetic and molecular modeling studies revealed that N5 was a competitive inhibitor of butyrylcholinesterase and interacted with the active sites of human acetylcholinesterase and human butyrylcholinesterase enzymes. NM15 and N5 were identified as lead PDCs based on their enhanced antioxidant and cholinesterase inhibitory activity, respectively. Overall, this work demonstrates the potential use of PDCs as treatment options for neurodegenerative diseases.

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Polymer–drug conjugates as nano-sized multi-targeting systems for the treatment of Alzheimer's disease

Abstract: Alzheimer’s disease (AD) is a progressive, neurodegenerative condition. There are clear markers for the presence and progression of the disease, including β-amyloid (Aβ) plaques and Tau tangles, with many potential...

Cited by 3 publications

References 117 publications

Polymer–drug and polymer–protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications

Polymer–drug and polymer–protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications

Hydroxyapatite–polymer nanocomposites for drug delivery applications: A mini review

Synthesis and Evaluation of Polymer-Drug Conjugates as Potential Antioxidants and Cholinesterase Inhibitors for Neurodegenerative Diseases

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