New types of synthetic infusion solutions. III. Elimination and retention of poly‐[<i>N</i>‐(2‐hydroxypropyl)methacrylamide] in a test organism

Sprincl, L; Exner, J.; Stĕrba, O; Kopeček, Jindřich

doi:10.1002/jbm.820100612

Cited by 99 publications

(22 citation statements)

References 23 publications

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“…HPMA copolymers have been shown in other systems to be nonimmunogenic, biocompatible drug carriers [20,21]. Recent data from phase I clinical trials of HPMA copolymer-doxorubicin conjugates have demonstrated the biocompatibility of the conjugates in humans [22,23].…”

Section: Discussionmentioning

confidence: 99%

Biopolymer-based delivery systems for advanced imaging and skeletal tissue-specific therapeutics

et al. 2005

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There is considerable advantage in developing tissue-specific delivery systems for therapeutic and diagnostic applications. Synthetic water-soluble polymeric delivery systems have been developed to allow selective delivery of therapeutic and imaging agents to musculoskeletal tissues. For mineralized tissues, bone-targeting agents such as aspartic acid octapeptide could concentrate the polymer conjugates to bone surfaces including resorption sites, which was demonstrated with routine bone histomorphometry. For bone-associated soft tissues, other targeting approaches based on pathophysiological properties unique to the local tissue environment, such as the leaky vasculature in arthritic joints, were utilized to achieve the selective deposition of the polymeric delivery systems to the desired sites. For this study, magnetic resonance imaging (MRI) was used to assess real-time pharmacokinetics and biodistribution of the MRI contrast agent conjugated polymer in major organs including skeletal tissues. The MRI data were then correlated with other standard imaging methods such as pQCT and DXA as well as routine histopathology and skeletal histomorphometry. Clearly, biopolymeric delivery systems may be used to improve the pharmacological and pharmacokinetic properties of different therapeutic agents for musculoskeletal diseases such as osteoporosis and arthritis. In addition, this or related technologies may also be useful to improve diagnosis and medical imaging with positron emission tomography, gamma scintigraphy, or other technologies.

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Section: Discussionmentioning

confidence: 99%

Biopolymer-based delivery systems for advanced imaging and skeletal tissue-specific therapeutics

et al. 2005

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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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“…Hydroxypropylmethacrylamide polymers were originally developed as potential plasma expanders and have a long safety record in man (6,7). The initial studies of the use of hydroxypropylmethacrylamide copolymers as potential delivery systems for Pt-containing drugs were reported by Duncan et al (8) who constructed an hydroxypropylmethacrylamide copolymer to which cisplatin was linked via a tetrapeptide GFLG coupled to an ethylenediamine chelating group.…”

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confidence: 99%

Preclinical Efficacy and Pharmacokinetics of AP5346, A Novel Diaminocyclohexane-Platinum Tumor-Targeting Drug Delivery System

Rice¹,

Gerberich²,

Nowotnik³

et al. 2006

Clinical Cancer Research

103

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Purpose: AP5346 is designed to target a diaminocyclohexane platinum (Pt) moiety to tumors through pH-sensitive linkage to a 25 kDa hydroxypropylmethacrylamide polymer. The goal of these studies was to determine the rate of release of Pt as a function of pH, the antitumor activity, and plasma and tumor pharmacokinetics of AP5346 in preclinical models. Experimental Design: Antitumor activity was assessed in mice bearing B16F10 melanoma and M5076 and 2008 ovarian carcinomas. Pt levels in plasma, tumors, and tumor DNA were measured by atomic absorption and inductively coupled plasma mass spectrometry. Results: AP5346 did not release Pt when suspended in 5% dextrose and released only 3.5% of its Pt in 24 hours in buffer at pH 7.4; the rate of release was 7-fold higher at pH 5.4. When given at their respective maximum tolerated doses, the antitumor activity of AP5346 was superior to that of oxaliplatin against both the B16 melanoma and 2008 human ovarian carcinoma. It was more effective than cisplatin in both cisplatin-sensitive and cisplatin-resistant variants of the M5076 tumor. When given at equitoxic doses, the peak plasma concentration was 25-fold higher, and AUC (0-1) was 93 times higher, for AP5346 than for oxaliplatin. AP5346 delivered 16.3-fold more Pt to the tumor and 14.2-fold more Pt to tumor DNA than oxaliplatin based on AUC . Conclusions: AP5346 has a substantially better therapeutic index than oxaliplatin. AP5346 produced a marked increase in the delivery of diaminocyclohexane Pt to the tumor and tumor DNA over and above that attainable with oxaliplatin.

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New types of synthetic infusion solutions. III. Elimination and retention of poly‐[N‐(2‐hydroxypropyl)methacrylamide] in a test organism

Cited by 99 publications

References 23 publications

Biopolymer-based delivery systems for advanced imaging and skeletal tissue-specific therapeutics

Biopolymer-based delivery systems for advanced imaging and skeletal tissue-specific therapeutics

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

Preclinical Efficacy and Pharmacokinetics of AP5346, A Novel Diaminocyclohexane-Platinum Tumor-Targeting Drug Delivery System

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