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Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

Site-Targeted Drug Delivery Systems: Polymeric Carriers

Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
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Modified-release dosage forms are designed to address the limitations of drugs with short biological half-lives. These forms maintain stable therapeutic drug concentrations over extended periods, reducing the need for frequent dosing. A consistent drug level helps minimize peak-trough fluctuations, which can reduce adverse effects, lower the risk of drug resistance, and improve overall treatment effectiveness.One common type of modified-release form is the extended-release (ER) formulation. ER...
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Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...
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Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
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Targeted Coacervates Enabled by Polyphenol-Peptide Networks for Therapeutic Delivery.

Linli Jiang1,2, Qiantao Song3, Zhixing Lin4,5

  • 1West China Hospital of Stomatology, College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, China.

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Researchers engineered polyphenol-peptide networks (PC@PPNs) to coat peptide coacervates (PCs), enhancing stability and enabling targeted intracellular delivery of therapeutics. This breakthrough improves drug delivery for various biomolecules.

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery Systems

Background:

  • Intracellular delivery of therapeutic biomolecules is hindered by challenges like poor stability and nonspecific cellular uptake.
  • Coacervates offer high loading capacity but suffer from instability and uncontrolled release, limiting their therapeutic potential.

Purpose of the Study:

  • To develop a versatile surface-engineering strategy for coacervates to improve stability and achieve programmable cell targeting and precise intracellular delivery.
  • To create a functional coacervate platform for diverse therapeutic cargos, including proteins and nucleic acids.

Main Methods:

  • Peptide coacervates (PCs) were coated with polyphenol-peptide networks (PC@PPNs) to encapsulate various cargos (fluorophores, proteins, peptides, DNA).
  • PC@PPNs were designed for dual pH- and glutathione-responsive disassembly to facilitate endosomal escape and cytosolic release.
  • Cell-specific targeting was achieved by incorporating targeting peptides into the polyphenol-peptide networks.

Main Results:

  • PC@PPNs demonstrated improved stability and successful encapsulation of diverse therapeutic cargos.
  • The dual-responsive PC@PPNs facilitated endosomal escape and controlled cytosolic release of cargo.
  • Incorporating HER2-targeting peptides enhanced PC@PPN association with HER2-overexpressing SKOV3 cells from 14% to 75%.
  • In vivo studies showed significant tumor size reduction in HER2-overexpressing models, validating cell-specific targeting.

Conclusions:

  • Surface engineering of coacervates with polyphenol-peptide networks offers a robust strategy to enhance stability and enable programmable targeting.
  • This approach advances the development of coacervates as versatile and programmable platforms for precise intracellular delivery of therapeutics.
  • The engineered coacervates show promise for targeted cancer therapy and other applications requiring efficient intracellular delivery.