The overview covers the discovery of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, initial studies on their synthesis, evaluation of biological properties, and explorations of their potential as carriers of biologically active compounds in general and anticancer drugs in particular. The focus is on the research in the authors' laboratory - the development of macromolecular therapeutics for the treatment of cancer and musculoskeletal diseases. In addition, the evaluation of HPMA (co)polymers as building blocks of modified and new biomaterials is presented: the utilization of semitelechelic poly(HPMA) and HPMA copolymers for the modification of biomaterial and protein surfaces and the design of hybrid block and graft HPMA copolymers that self-assemble into smart hydrogels. Finally, suggestions for the design of second-generation macromolecular therapeutics are portrayed.
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http://dx.doi.org/10.1016/j.addr.2009.10.004 | DOI Listing |
ACS Appl Bio Mater
November 2024
Institute of Chemistry and Biochemistry, Freie Universitaet Berlin, Takustr. 3, 14195 Berlin, Germany.
Thermoresponsive polymer coatings on cell culture substrates enable noninvasive cell detachment and cell sheet fabrication for biomedical applications. Optimized coatings should support controlled culture and detachment of various cell types and allow chemical modifications, e.g.
View Article and Find Full Text PDFMol Hum Reprod
November 2024
Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL, USA.
Currently, there are no placenta-targeted treatments to alter the in utero environment for administration to pregnant women who receive a diagnosis of fetal growth restriction (FGR). Water-soluble polymers have a distinguished record of clinical relevance outside of pregnancy. We have demonstrated the effective delivery of polymer-based nanoparticles containing a non-viral human insulin-like growth factor 1 (IGF1) transgene to correct placental insufficiency in small animal models of FGR.
View Article and Find Full Text PDFJ Control Release
December 2024
Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA; Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:
Death Receptor 5 (DR5) targeted therapies offer significant promise due to their pivotal role in mediating the extrinsic pathway of apoptosis. Despite DR5 overexpression in various malignancies and the potential of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), clinical applications of anti-DR5 monoclonal antibodies (mAbs) have been hampered by suboptimal outcomes potentially due to lack of receptor clustering. To address the limitation, we developed N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based conjugates integrating multiple copies of DR5-targeting peptide (cyclic WDCLDNRIGRRQCVKL; cDR5) to enhance receptor clustering and apoptosis.
View Article and Find Full Text PDFInt J Pharm
November 2024
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského náměstí 2, 162 00 Prague 6, Czech Republic. Electronic address:
The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system.
View Article and Find Full Text PDFMol Pharm
October 2024
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
Psoriasis is a chronic immune-mediated inflammatory skin disease, affecting ∼ 3% of the US population. Although multiple new systemic therapies have been introduced for the treatment of psoriatic skin disease, topical and intralesional glucocorticoids (GCs) continue to be used as effective psoriasis therapies. Their clinical utility, however, has been hampered by significant adverse effects, including skin atrophy and pigmentation as well as elevated blood glucose levels and hypertension.
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