Jindřich Kopeček

Osteosarcoma is a malignancy of the bone that primarily affects adolescents. Current treatments retain mortality rates, which are higher than average cancer mortality rates for the adolescent age group. We designed a micellar delivery system with the aim to increase drug accumulation in the tumor and potentially reduce side effects associated with chemotherapy. The design features are the use of the hydrophilic D-aspartic acid octapeptide as both the effective targeting agent as well as the hydrophilic micelle corona. Micelle stabilization was accomplished by binding of model drug (doxorubicin) via an acid-sensitive hydrazone bond and incorporating one to four 11-aminoundecanoic acid (AUA) moieties to manipulate the hydrophobic/hydrophilic ratio. Four micelle-forming unimers have been synthesized and their self-assembly into micelles was evaluated. Size of the micelles could be modified by changing the architecture of the unimers from linear to branched. The stability of the micelles increased with increasing content of AUA moieties. Adsorption of all micelles to hydroxyapatite occurred rapidly. Doxorubicin release occurred at pH 5.5, whereas no release was detected at pH 7.4. Cytotoxicity toward human osteosarcoma Saos-2 cells correlated with drug release data.

Conjugate

10.1021/bc500392x

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Citations (49)

Synthesis of N-(2-hydroxypr opyl) methacrylamide copolymers with antimicrobial activity

Biomaterials (1983)

Mikhail V. Solovsky Karel Ulbrich Jindřich Kopeček

Methacrylamide

10.1016/0142-9612(83)90069-8

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Citations (49)

Polymers containing enzymatically degradable bonds, 2. Poly[N‐(2‐hydroxypropyl)methacrylamide] chains connected by oligopeptide sequences cleavable by chymotrypsin

Die Makromolekulare Chemie (1981)

Pavla Rejmanová B. Obereigner Jindřich Kopeček

Abstract Copolymers of N ‐(2‐hydroxypropyl)methacrylamide ( 1 ) with p ‐nitrophenyl esters of N ‐methacryloylated oligopeptides ( 2–16 ) were prepared. These copolymers were crosslinked below the gel point by diamines ( 17–27 ). The crosslinks connecting poly[ N ‐(2‐hydroxypropyl)methacrylamide] chains contained an oligopeptidic sequence of 2–4 amino acids, cleavable by α‐chymotrypsin: ‐Gly‐X‐Y‐ (X… Gly, Ala, β‐Ala, Val, Leu, Ile, Phe, D ‐Phe; Y… Phe, Tyr), ‐Gly‐Gly‐Phe‐Y‐; ‐U‐Gly‐Val‐Phe‐ (U… Ala, Gly); ‐Gly‐Phe‐W‐ (W… Ala, Gly, D ‐Phe); ‐Gly‐Phe‐Ala‐U‐. The changes in the distribution of molecular weights of the studied copolymers, after incubation with α‐chymotrypsin, allowed us to estimate the amount of degradable crosslinks and to determine the relationship between the structure and cleavability. The results are interpreted from the viewpoint of the contribution of subsite (S‐P) interactions to the degradability of the studied polymers.

Methacrylamide

Oligopeptide

Side chain

10.1002/macp.1981.021820703

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Citations (57)

Hydrophilic biomaterials: From crosslinked and self-assembled hydrogels to polymer-drug conjugates and drug-free macromolecular therapeutics

Journal of Controlled Release (2024)

Jindřich Kopeček

Biocompatible material

10.1016/j.jconrel.2024.05.012

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