Cardiological Biopharmaceuticals in the Conception of Drug Targeting Delivery: Practical Results and Research Perspectives

Abstract

The results of the clinical use of thrombolytic and antithrombotic preparations developed on the basis of protein conjugates obtained within the framework of the conception of drug targeting delivery in the organism are considered. A decrease has been noted in the number of biomedical projects focused on these derivatives as a result of various factors: the significant depletion of financial and organizational funds, the saturation of the pharmaceutical market with preparations of this kind, and the appearance of original means for interventional procedures. Factors that actively facilitate the conspicuous potentiation of the efficacy of bioconjugates were revealed: the biomedical testing of protein domains and their selected combinations, the optimization of molecular sizes for the bioconjugates obtained, the density of target localization, the application of cell adhesion molecules as targets, and the application of connected enzyme activities. Enzyme antioxidants and the opportunity for further elaboration of the drug delivery conception via the elucidation and formation of therapeutic targets for effective drug reactions by means of pharmacological pre- and postconditioning of myocardium arouse significant interest.

Stratification of chondroitin sulfate binding sites in 3D-model of bovine testicular hyaluronidase and effective size of glycosaminoglycan coat of the modified protein

“…The relevance of this field has increased due to the rapid advances in biotechnology, bioengineering, and biopharmacology. The results of practical implementa tion of enzyme derivatives are very significant in medi cine, in particular cardiology, oncology, and gastroen terology [1,2]. Scientific interest has also increased with the development of glycobiology [3].…”

Widening and Elaboration of Consecutive Research into Therapeutic Antioxidant Enzyme Derivatives

“…and to add to them new properties (ability to concentrate in the damaged area, reduce toxicity, etc.) has been successfully used for a long time [ 3 , 4 ]. Covalent binding of low-molecular-mass heparin to Cu, Zn-superoxide dismutase increased the enzyme stability in acid and alkaline media as well as its resistance to trypsinolysis and temperature [ 11 ].…”

“…Modification with the amphiphilic polymer poly(N-acryloylmorpholine) was used as an alternative to PEGylation [ 18 ]. Recent evidence demonstrates the diversity and effectiveness of protein modifications for the development of new medical protein derivatives [ 3 , 4 , 19 , 20 ] and evaluates the role of protein modifications in various physiological and pathological processes [ 21 ].…”

“…Protein-based products for biomedical purposes (compositions, combined drugs) [ 22 , 23 ] were determined, new methods of their production and isolation were suggested [ 24 ], and the concordance between structural modifications of biopharmaceutics and their therapeutic effectiveness and safety was evaluated [ 25 ]. It should be noted that development of protein drugs has numerous stages, such as choice of modification method, optimization of modification, analysis of the active agent binding and release, cytotoxicity and toxicological parameters, statistically significant confirmation of therapeutic effects in vivo , study of biodistribution of derivatives, and evaluation of technological approaches [ 4 , 10 ]. This has provoked a vast array of publications in biochemical, physiological, clinical, and biotechnological journals, which accelerated distribution of information but hampered a presentation of consecutive evidence concerning a given pharmaceutical agent.…”

“…For instance, investigation and development of plasminogen activators provided a current set of protein preparations for clinical thrombolysis [ 3 ]. Their effectiveness urges further improvements, such as a decrease in molecular mass (compared with parent molecules) or an increase in it upon construction of new modified agents [ 4 ]. Fast development of glycobiology [ 5 , 6 ] leads to new approaches and targets for the future protein therapy.…”