Polycaprolactone/α-Cyclodextrin Polyrotaxanes with Cellular Uptake Enhancing Properties

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: 13(10), P. 3471 - 3482

Published: Jan. 1, 2025

Biodegradable poly(ε-caprolactone) (PCL) was rotaxanated with α-cyclodextrin (α-CD) and an α-CD/2-hydroxypropyl-α-CD (HP-α-CD) mixture. Stoppering achieved using 2-mercaptosuccinic acid (MSA) via disulfide linkage. The structures of these polymeric supramolecular entities were confirmed by 1H NMR, 75-80 wt% threaded CD, while the molar mass polyrotaxanes around 18 kDa, determined gel permeation chromatography. aqueous solubility as low 20.2 ± 1.2 g L-1 for α-CD-based polyrotaxane but considerably increased to 74.7 6.0 introduction HP-α-CD into axis. Dethreading triggered removal stopper molecules disulfide-exchange reactions glutathione. Additionally, polyester axis proved be fully degradable lipase. Cellular uptake investigated flow cytometry confocal microscopy. results showed almost up 50-fold higher cellular than free CD. These end-stoppered biodegradable PCL represent a promising tool intracellular delivery CDs offer novel treatment possibilities lysosomal storage dysfunctions.

Language: Английский

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Sustainable Revolution: AI-Driven Enhancements for Composite Polymer Processing and Optimization in Intelligent Food Packaging

Food and Bioprocess Technology, Journal Year: 2024, Volume and Issue: unknown

Published: May 30, 2024

Language: Английский

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Polymeric nanoparticles in colorectal cancer

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 203 - 231

Published: Jan. 1, 2024

Language: Английский

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Beyond Nanoparticle‐Based Intracellular Drug Delivery: Cytosol/Organelle‐Targeted Drug Release and Therapeutic Synergism

Macromolecular Bioscience, Journal Year: 2024, Volume and Issue: 24(7)

Published: March 16, 2024

Nanoparticle (NP)-based drug delivery systems are conceived to solve poor water-solubility and chemical/physical instability, their purpose expanded target specific sites for maximizing therapeutic effects minimizing unwanted events of payloads. Targeted also narrowed from organs/tissues cells cytosol/organelles. Beyond site targeting, the particular release payloads at is growing in importance. This review overviews various issues general strategies during multiple steps, preparation drug-loaded NPs In particular, this focuses on current "first" "later" drugs cytosol or organelles interest using stimuli sites. Recognizing distinguishing presence/absence differences concentration/level/activity one place those another applied stimuli-triggered via bond cleavage nanostructural transition. addition, future directions understanding intracellular balance counter-stimuli demonstrated synergize released stimuli-sensitive NPs.

Language: Английский

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Impact of mechanical cues on key cell functions and cell-nanoparticle interactions

Discover Nano, Journal Year: 2024, Volume and Issue: 19(1)

Published: June 22, 2024

Abstract In recent years, it has been recognized that mechanical forces play an important regulative role in living organisms and possess a direct impact on crucial cell functions, ranging from growth to maintenance of tissue homeostasis. Advancements mechanobiology have revealed the profound signals diverse cellular responses are type specific. Notably, numerous studies elucidated pivotal different cues as regulatory factors influencing various processes, including spreading, locomotion, differentiation, proliferation. Given these insights, is unsurprising cells regulated by physical intricately linked modulation nanoparticle uptake kinetics processing. This complex interplay underscores significance understanding microenvironment shaping behaviors and, consequently, how interact with process nanoparticles. Nevertheless, our knowledge localized affect internalization processing nanoparticles remains rather limited. A significant gap exists literature concerning systematic analysis might bias interactions between cells. Hence, aim this review provide comprehensive critical existing regarding influence complicated dynamics cell-nanoparticle interactions. By addressing gap, we would like contribute detailed

Language: Английский

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Functional nanoemulsions: Controllable low-energy nanoemulsification and advanced biomedical application

Chinese Chemical Letters, Journal Year: 2023, Volume and Issue: 35(2), P. 108710 - 108710

Published: June 22, 2023

Language: Английский

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Peptide-coated DNA nanostructures as a platform for control of lysosomal function in cells

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 498, P. 155633 - 155633

Published: Sept. 12, 2024

Language: Английский

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Improving the treatment of pompe disease with enzyme replacement therapy: current strategies and clinical evidence

Expert Opinion on Pharmacotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Pompe disease (PD) is a rare genetic disorder that leads to intralysosomal glycogen accumulation because of deficiency in the lysosomal enzyme acid α-glucosidase (GAA), which required break down glucose. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) supplies exogenous reduce deposits, thereby improving motor and respiratory functioning. The first approved ERT for PD was rhGAA alglucosidase alfa. Limitations associated this treatment led development two other rhGAAs: avalglucosidase alfa cipaglucosidase This review describes limitations focuses on strategies used overcome these limitations, including conjugation multiple synthetic bis-M6P - containing hexasaccharides sialic acids present enzyme, thus enhancing M6PR targeting, uptake, clearance, therapeutic outcomes. Efficacy safety late-onset infantile-onset are also discussed. A brief overview newest ERT, alfa, provided. While continues improve more effective enzymes like future lies integrated approaches combine different modalities (gene therapy, substrate reduction therapy) use biomarkers individualize treatment.

Language: Английский

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New Cellular Models to Support Preclinical Studies on ICAM-1-Targeted Drug Delivery

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 101, P. 106170 - 106170

Published: Sept. 10, 2024

Language: Английский

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Role of the Lactide:Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders

Journal of Functional Biomaterials, Journal Year: 2023, Volume and Issue: 14(9), P. 440 - 440

Published: Aug. 25, 2023

Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) lysosomal storage disorders (LSDs). This study examined how copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under conditions. Hyaluronidase, deficient mucopolysaccharidosis IX, was encapsulated NPs synthesized using 50:50, 60:40, or 75:25 copolymers. All had diameters compatible with cellular transport (≤168 nm) polydispersity indexes (≤0.16) ζ-potentials (≤-35 mV) colloidal stability. Yet, their efficiency varied, 60:40 having lowest highest EE, respectively (15% vs. 28%). Under conditions, 50:50 degraded fastest (41% 1 week), as expected, presence a targeting antibody coat did not alter this result. Additionally, destabilized (<1 week) because smaller diameter, destabilize 4 weeks. formulations presented burst conditions (56-78% original load within 30 min), releasing an additional small fraction after week 1. provided weeks sustained catalytic activity, sufficient to fully degrade substrate. Altogether, NP formulation is preferred given its higher represent valid alternative, while stability may impair lysosomes. These results can guide future aiming translate PLGA NP-based ERT other LSDs.

Language: Английский

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