Structural and chemical aspects of HPMA copolymers as drug carriers☆

Ulbrich, Karel; Šubr, Vladimír

doi:10.1016/j.addr.2009.10.007

Cited by 181 publications

(161 citation statements)

References 193 publications

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“…One promising compound fulfilling these requirements is poly-N-(2-hydroxypropyl)methacrylamide (p [HPMA]) polymers that have been already tested in preclinical as well as clinical studies. [7][8][9] Further development of these hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA) homopolymers led to the design of copolymers containing lipophilic lauryl methacrylate (LMA) segments within the HPMA backbone. These HPMA-LMA copolymers (p(HPMA)-co-p(LMA) and p(HPMA)-b-p(LMA) copolymers) have been shown to improve the drug transport through the blood-brain barrier.…”

Section: Introductionmentioning

confidence: 99%

Endocytotic uptake of HPMA-based polymers by different cancer cells: impact of extracellular acidosis and hypoxia

Gündel¹,

Allmeroth²,

Reime³

et al. 2017

IJN

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Background Polymeric nanoparticles allow to selectively transport chemotherapeutic drugs to the tumor tissue. These nanocarriers have to be taken up into the cells to release the drug. In addition, tumors often show pathological metabolic characteristics (hypoxia and acidosis) which might affect the polymer endocytosis. Materials and methods Six different N -(2-hydroxypropyl)methacrylamide (HPMA)-based polymer structures (homopolymer as well as random and block copolymers with lauryl methacrylate containing hydrophobic side chains) varying in molecular weight and size were analyzed in two different tumor models. The cellular uptake of fluorescence-labeled polymers was measured under hypoxic (pO 2 ≈1.5 mmHg) and acidic (pH 6.6) conditions. By using specific inhibitors, different endocytotic routes (macropinocytosis and clathrin-mediated, dynamin-dependent, cholesterol-dependent endocytosis) were analyzed separately. Results The current results revealed that the polymer uptake depends on the molecular structure, molecular weight and tumor line used. In AT1 cells, the uptake of random copolymer was five times stronger than the homopolymer, whereas in Walker-256 cells, the uptake of all polymers was much stronger, but this was independent of the molecular structure and size. Acidosis increased the uptake of random copolymer in AT1 cells but reduced the intracellular accumulation of homopolymer and block copolymer. Hypoxia reduced the uptake of all polymers in Walker-256 cells. Hydrophilic polymers (homopolymer and block copolymer) were taken up by all endocytotic routes studied, whereas the more lipophilic random copolymer seemed to be taken up preferentially by cholesterol- and dynamin-dependent endocytosis. Conclusion The study indicates that numerous parameters of the polymer (structure, size) and of the tumor (perfusion, vascular permeability, pH, pO 2 ) modulate drug delivery, which makes it difficult to select the appropriate polymer for the individual patient.

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Section: Introductionmentioning

confidence: 99%

Endocytotic uptake of HPMA-based polymers by different cancer cells: impact of extracellular acidosis and hypoxia

Gündel¹,

Allmeroth²,

Reime³

et al. 2017

IJN

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“…Poly-N-(2-hydroxypropyl) methacrylamide, pHPMA, is a neutral and biocompatible polymeric carrier used to prepare different soluble drug conjugates with a high residence time in plasma and low tissue distribution compared to other polymer systems [1][2][3][4][5]. Because of this well-known performance in physiological media, this neutral polymer has been studied for more than a decade as sterical stabilizer of polycation-DNA complexes or polyplexes, in order to modulate their positive charge density and hydrophilia, in an attempt to avoid nonspecific interactions with both the cellular membrane and plasma components.…”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of pendant hydroxypropyl and pyrrolidine moieties randomly distributed along polymethacrylamide backbones on in vitro DNA-transfection

Redondo

Velasco

Pérez-Perrino

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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“…[23,24] The choice of an appropriate polymeric carrier is crucial for systemic administration and 2-hydroxypropyl methacrylamide (HPMA)-based polymers have drawn special attention. [25,26] The linear or branched polymer chain usually serves as the structural component of a conjugate. Most of the clinically tested polymer conjugates have the typical structure consisting of a polymer backbone, a linker and the bioactive unit.…”

Section: Introductionmentioning

confidence: 99%

Polymer Conjugates of Photoinducible CO‐Releasing Molecules

et al. 2011

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Keywords: Carbon monoxide / Carbonyl ligands / Polymer conjugates / Manganese / EPR effect / Cytotoxicity CO-releasing molecules (CORMs) were coordinated to polymeric carrier systems for passive transport to tumour tissue or sites of inflammation, as described by the enhanced permeability and retention (EPR) effect. The developed conjugates consist of an organometallic fac-Mn(CO) 3 fragment, which is bound to a methacrylate or methacrylamide polymer backbone by bis(pyridylmethyl)amine-type ligands. The resulting Mn(CO) 3 -polymer conjugates were investigated as photoinducible CO-releasing molecules (photoCORMs). Furthermore, three model complexes [LMn(CO) 3 ]O 2 SCF 3

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Structural and chemical aspects of HPMA copolymers as drug carriers☆

Cited by 181 publications

References 193 publications

Endocytotic uptake of HPMA-based polymers by different cancer cells: impact of extracellular acidosis and hypoxia

Endocytotic uptake of HPMA-based polymers by different cancer cells: impact of extracellular acidosis and hypoxia

Synergistic effect of pendant hydroxypropyl and pyrrolidine moieties randomly distributed along polymethacrylamide backbones on in vitro DNA-transfection

Polymer Conjugates of Photoinducible CO‐Releasing Molecules

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