Use of Self-Assembled Colloidal Prodrug Nanoparticles for Controlled Drug Delivery of Anticancer, Antifibrotic and Antibacterial Mitomycin

Abstract

Herein we present the synthesis of a polymeric prodrug nanomaterial capable of spontaneous, self-assembled nanoparticle formation and of the conjugation (encapsulation) of drugs with amino and/or carboxyl and/or hydroxyl groups via ester and/or amide linkage. Mitomycin C (MMC) a versatile drug with antibiotic, antibacterial and antineoplastic properties, was used to prove this concept. The in vitro drug release experiments showed a fast release for the pure MMC (k = 49.59 h−n); however, a significantly lower MMC dissolution rate (k = 2.25, 1.46, and 1.35 h−n) was obtained for the nanoparticles with increased cross-link density (3, 10, 21%). The successful modification and conjugation reactions were confirmed using FTIR and EDX measurements, while the mucoadhesive properties of the self-assembled particles synthesized in a simple one-pot reaction were proved by rheological measurement. The prepared biocompatible polymeric prodrugs are very promising and applicable as a drug delivery system (DDS) and useful in the area of cancer treatment.

An Injectable Composite Hydrogel of Verteporfin‐Bonded Carboxymethyl Chitosan and Oxidized Sodium Alginate Facilitates Scarless Full‐Thickness Skin Regeneration

“…The release of verteporfin may be resulted from the hydrolysis of amino bond between verteporfin and CMCS. [ 41 ]…”

Új minimálinvazív kezelési lehetőségek jó- és rosszindulatú fül-orr-gégészeti betegségekben nanoszerkezetű hatóanyag-leadó rendszerek alkalmazásával

“…A poli(vinil-alkohol) (PVA)-alapú DDS szintézise során borostyánkősav-anhidriddel úgy módosítottuk a kiindulási makromolekula-láncot, hogy az egyre növekvő mennyiségben (rendre 0,5, 1,65 és 3,4 mmol/g) karboxil (COOH)-csoportokat tartalmazzon, amelyek a polimerláncon található hidroxil (OH)-csoportokkal megfelelő körülmények között észterkötéseket alakítanak ki (1. ábra). A makromolekula mukoadhezív tulajdonságát ciszteaminnal biztosítottuk, míg az MMC, illetve ciszplatin hatóanyag-molekulákat szintén kémiai kötésekkel kapcsoltuk a polimerláncra [27]. Szabad MMC 0,254 0,029 ± 0,001 0,270 0,041 ± 0,002 0,273 0,026 ± 0,006 0,275 0,05 ± 0,045 Kontroll 0,000 0,000 0,000 0,000 0,000 0,000 0,000 0,000 PVA-MMC (3%) 0,063 0,014 ± 0,001 0,140 0,022 ± 0,007 0,173 0,043 ± 0,025 0,188 0,054 ± 0,029 PVA-MMC (21%) 0,029 0,037 ± 0,004 0,065 0,038 ± 0,01 0,089 0,039 ± 0,007 0,097 0,029 ± 0,004 konc = koncentráció; MMC = mitomicin C; PVA = poli(vinil-alkohol)…”

Self-Assembling Injectable Hydrogel for Controlled Drug Delivery of Antimuscular Atrophy Drug Tilorone

“…The successful modification of the initial polymers was confirmed by the FTIR measurements as shown in Figure 2. The main characteristic peaks of PVA were 3280 cm −1 (O-H stretching vibration), 2960 cm −1 (CH 2 asymmetric stretching vibration), 2925 cm −1 (CH 2 symmetric stretching vibration), 1735 cm −1 (C=O carbonyl stretching vibration), 1425 cm −1 (C-H bending vibration of CH 2 ), 1380 cm −1 (C-H deformation vibration), 1325 cm −1 (CH 2 wagging vibration), 1245 cm −1 (C-O-C stretching vibration), 1100 cm −1 (C-O stretching of acetyl groups), and 840 cm −1 (C-C stretching vibration) [24,40,41]. The modification reaction was confirmed by the appearance of the C=O stretching vibration of the aldehyde at 1705 cm -1 which overlapped with the ester (C=O) carbonyl at 1730 cm -1 .…”

“…Thiolated macromolecules were one of the most efficient mucoadhesive polymers due to their ease in forming disulfide bonds (covalent bonds) with the cysteine-rich subdomains of the mucus gel layer through the thiol-disulfide exchange mechanism in addition to the van der Waals' forces and hydrogen bonds that led to an increase in the residence time of the polymers inside the body and that improved bioavailability [39,40]. In order to provide free thiol groups for the generated hydrogel, the 3-mercaptopropionate moiety was used to modify the NH 2 groups of CHIT via amide bond formation.…”

“…In order to provide free thiol groups for the generated hydrogel, the 3-mercaptopropionate moiety was used to modify the NH 2 groups of CHIT via amide bond formation. These free terminal thiol groups enabled the hydrogel to be able to form covalent S-S bonds with the SH groups of the mucous membrane [39,40]. The thiol content of CHIT-SH was evaluated using Ellman's reagent method, with a result of 201.85 ± 12 µmol/g, as well as the EDX measurement, showing the presence of a high sulfur content due to the thiol group of the 3-mercaptopropionate moiety of CHIT-SH as shown in Figure 6 compared to pure CHIT, which exhibited no sign of the existence of the sulfur element.…”