Biodegradable nanoparticles based on stearic acid-modified poly(glycerol adipate) (PGAS) are promising carriers for drug delivery. In order to investigate the impact of the particle interface characteristics on the biological fate, PGAS nanoparticles are covalently and noncovalently coated with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. HPMA copolymer-modified PGAS nanoparticles have similar particle sizes, but less negative zeta-potentials. Nanoparticles are double labeled with the fluorescent dyes DiR (noncovalently) and DYOMICS-676 (covalently bound to HPMA copolymer), and their biodistribution is investigated noninvasively by multispectral optical imaging. Both covalent and noncovalent coatings cause changes in the pharmacokinetics and biodistribution in healthy and tumor-bearing mice. In addition to the intended tumor accumulation, high signals of both fluorescent dyes are also observed in other organs, including liver, ovaries, adrenal glands, and bone. The unintended accumulation of nanocarriers needs further detailed and systematic investigations, especially with respect to the observed ovarian and adrenal gland accumulation.

• MeSH
• biologicky odbouratelné plasty chemie   MeSH
• buňky HT-29 MeSH
• fluorescenční barviva chemie   MeSH
• lidé MeSH
• methakryláty aplikace a dávkování   chemie   MeSH
• myši MeSH
• nádory farmakoterapie   genetika   patologie   MeSH
• nanočástice aplikace a dávkování   chemie   MeSH
• nosiče léků aplikace a dávkování   chemie   MeSH
• polyestery aplikace a dávkování   chemie   MeSH
• systémy cílené aplikace léků * MeSH
• tkáňová distribuce účinky léků   MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Here, we present the synthesis, physicochemical, and preliminary biological characterization of micellar polymer-betulinic acid (BA) conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carriers, enabling the controlled release of cytotoxic BA derivatives in solid tumors or tumor cells. Various HPMA copolymer conjugates differing in the structure of the spacer between the drug and the carrier were synthesized, all designed for pH-triggered drug release in tumor tissue or tumor cells. The high molecular weight of the micellar conjugates should improve the uptake of the drug in solid tumors due to the Enhanced permeability and retention (EPR) effect. Nevertheless, only the conjugate containing BA with methylated carboxyl groups enabled pH-dependent controlled release in vitro. Moreover, drug release led to the disassembly of the micellar structure, which facilitated elimination of the water-soluble HPMA copolymer carrier from the body by renal filtration. The methylated BA derivative and its polymer conjugate exhibited high cytostatic activity against DLD-1, HT-29, and HeLa carcinoma cell lines and enhanced tumor accumulation in HT-29 xenograft in mice.

• MeSH
• biologicky odbouratelné plasty chemie   MeSH
• doxorubicin aplikace a dávkování   chemie   MeSH
• lidé MeSH
• methakryláty aplikace a dávkování   chemie   MeSH
• micely MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   MeSH
• nosiče léků aplikace a dávkování   chemie   MeSH
• polymery aplikace a dávkování   chemie   MeSH
• proliferace buněk účinky léků   MeSH
• triterpeny aplikace a dávkování   chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH