Polymeric Conjugates for Drug Delivery

Larson, Nate; Ghandehari, Hamidreza

doi:10.1021/cm2031569

Cited by 530 publications

(422 citation statements)

References 203 publications

(404 reference statements)

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“…The attached substance is usually a particle, ligand, or stabilizer that improves solubility, pilots the drug, protects from the reticuloendothelial system, improves drug efficacy, or provides some other function [84]. The attached drug becomes effective after some objective is met (e.g., arrival at desired site), or the prodrug is exposed to an anticipated stimulus, triggering release.…”

Section: Polysaccharide Prodrug Complexesmentioning

confidence: 99%

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Self-assembled polysaccharide nanostructures for controlled-release applications

Myrick

Vendra

Krishnan

2014

Nanotechnology Reviews

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Self-assembling polysaccharide nanostructures have moved to the forefront of many fields due to their wide range of functional properties and unique advantages, including biocompatability and stimulus responsiveness. In particular, the field of controlled release, which involves influencing the location, concentration, and efficacy of active pharmaceutical ingredients (APIs), diagnostics, nutrients, or other bioactive compounds, has benefited from polysaccharide biomaterials. Nanostructure formation, stimulus responsiveness, and controlledrelease performance can be engineered through facile chemical functionalization and noncovalent intermolecular interactions. This review discusses polysaccharide nanoparticles, designed for targeted and time-controlled delivery of emerging APIs, with improved in vivo retention, stability, solubility, and permeability characteristics. Topics covered include nanoparticles of cyclodextrin and cyclodextrin-containing polymers, hydrophobically modified polysaccharides, polysaccharide nanoparticles that respond to pH, temperature, or light stimulus, polysaccharide prodrug complexes, polysaccharide complexes with lipids and proteins, and other polysaccharide polyelectrolyte complexes.

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Section: Polysaccharide Prodrug Complexesmentioning

confidence: 99%

“…These complexes also offer a different mode of release once activated, in comparison with the reservoir or core-shell-type systems, expanding realizable release profile possibilities. Reviews of polymer-drug conjugates [84,85] and recent clinical studies [86] are available.…”

Section: Polysaccharide Prodrug Complexesmentioning

confidence: 99%

Self-assembled polysaccharide nanostructures for controlled-release applications

Myrick

Vendra

Krishnan

2014

Nanotechnology Reviews

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“…c, d MALDI-ToF-MS analysis of monoPEGylated amylin (peak I) e, f MALDI-ToF-MS analysis of diPEGylated amylin (peak II). The details are described in the "MATERIAL AND METHODS" section result in peptide products with masses of 832 Da (amylin [12][13][14][15][16][17][18] ). As a consequence of the inherent Pd of mPEG derivatives, it is not possible to obtain a single, discrete molecular weight for the PEGylated peptide.…”

Section: Identification Of Pegylation Sitesmentioning

confidence: 99%

“…The addition of one or more PEG chains to a macromolecule can enhance its lifetime circulation and solubility and can also modify its biological activity (13)(14)(15)(16)(17). Amylin decays rapidly in plasma, with a half-life (t 0.5 ) of approximately 13 min (10); therefore, increasing the amylin t 0.5 would be a desirable strategy to achieve effective basal hormone restoration.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of PEGylated Amylin

et al. 2013

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Abstract. Amylin is a pancreatic hormone that plays important roles in overall metabolism and in glucose homeostasis. The therapeutic restoration of postprandial and basal amylin levels is highly desirable for patients with diabetes who need to avoid glucose excursions. Protein conjugation with polyethylene glycol (PEG) has long been known to be a convenient approach for extending the biological effects of biopharmaceuticals. We have investigated the reactivity of amylin with methoxy polyethylene glycol succinimidyl carbonate and methoxy polyethylene glycol succinimidyl propionate, which have an average molecular weight of 5 kDa. The reaction, which was conducted in both aqueous and organic (dimethyl sulfoxide) solvents, occurred within a few minutes and resulted in at least four detectable products with distinct kinetic phases. These results suggest a kinetic selectivity for PEGylation by succinimidyl derivatives; these derivatives exhibit enhanced reactivity with primary amine groups, as indicated by an evaluation of the remaining amino groups using fluorescamine. The analysis of tryptic fragments from mono-and diPEGylated amylin revealed that conjugation occurred within the 1-11 amino acid region, most likely at the two amine groups of Lys 1 . The reaction products were efficiently separated by C-18 reversed phase chromatography. Binding assays confirmed the ability of mono-and diPEGylated amylin to interact with the amylin co-receptor receptor activity-modifying protein 2. Subcutaneous administration in mice revealed the effectiveness of monoPEG-amylin and diPEG-amylin in reducing glycemia; both compounds exhibited prolonged action compared to unmodified amylin. These features suggest the potential use of PEGylated amylin to restore basal amylin levels.

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“…The key feature of a polymer-drug conjugate is that rather than containing a drug that is non-covalently encapsulating within a polymeric structure, the drug is physically conjugated to the polymeric carrier [1]. In this regard, problems associated with 'burst drug release' can be largely overcome and the drug can be covalently linked to the polymer via linkages that are specifically designed to liberate drug within certain structures, or at a predicted rate in vivo.…”

Section: Introductionmentioning

confidence: 99%

Polymer-drug conjugates as inhalable drug delivery systems: A review

Marasini

Haque

Kaminskas

2017

Current Opinion in Colloid & Interface Science

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Abstract:Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetics profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety with the lungs, which is closely linked to their retention time in the lungs. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments on several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps. Graphical abstract:

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Polymeric Conjugates for Drug Delivery

Cited by 530 publications

References 203 publications

Self-assembled polysaccharide nanostructures for controlled-release applications

Self-assembled polysaccharide nanostructures for controlled-release applications

Preparation and Characterization of PEGylated Amylin

Polymer-drug conjugates as inhalable drug delivery systems: A review

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