Ionic Liquid-Based Polymer Matrices for Single and Dual Drug Delivery: Impact of Structural Topology on Characteristics and In Vitro Delivery Efficiency.

Previously reported amphiphilic linear and graft copolymers, derived from the ionic liquid [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA_Cl‾), along with their conjugates obtained through modification either before or after polymerization with p-aminosalicylate anions (TMAMA_PAS‾), were employed as matrices in drug delivery systems (DDSs). Based on the counterion type in TMAMA units, they were categorized into single drug systems, manifesting as ionic polymers with chloride counterions and loaded isoniazid (ISO), and dual drug systems, featuring ISO loaded in self-assembled PAS conjugates. The amphiphilic nature of these copolymers was substantiated through the determination of the critical micelle concentration (CMC), revealing an increase in values post-ion exchange (from 0.011-0.063 mg/mL to 0.027-0.181 mg/mL). The self-assembling properties were favorable for ISO encapsulation, with drug loading content (DLC) ranging between 15 and 85% in both single and dual systems. In vitro studies indicated ISO release percentages between 16 and 61% and PAS release percentages between 20 and 98%. Basic cytotoxicity assessments using the 2,5-diphenyl-2H-tetrazolium bromide (MTT) test affirmed the non-toxicity of the studied systems toward human non-tumorigenic lung epithelial cell line (BEAS-2B) cell lines, particularly in the case of dual systems bearing both ISO and PAS simultaneously. These results confirmed the effectiveness of polymeric carriers in drug delivery, demonstrating their potential for co-delivery in combination therapy.

Chitosan-Grafted-Poly(N-vinylcaprolactam)-Decorated Fe3O4@SiO2 Core-Shell Nanoformulation as an Efficient Drug Delivery System for Poorly Soluble Drugs.

Hydrocortisone, a commonly used anti-inflammatory drug, has limited aqueous solubility and several side effects. To address this challenge, as a proof-of-concept, this article demonstrates the development of a controlled-release drug delivery system (DDS) for hydrocortisone using chitosan-grafted poly(N-vinylcaprolactam) (CS-g-PNVCL)-coated core-shell Fe3O4@SiO2 nanoformulations (NFs). Reported magnetic nanoparticles (NPs) were synthesized and modified with silica, PNVCL, and CS precursors to enhance the biocompatibility of DDS and drug-loading efficiency. The release rate of hydrocortisone from Fe3O4@SiO2@CS-g-PNVCL NFs was observed to be higher at lower pH values, and the smart polymer coating demonstrated temperature responsiveness, facilitating drug release at higher temperatures. Fe3O4@SiO2@CS-g-PNVCL NFs exhibited a cell viability of around 97.2 to 87.3% (5-100 µg/mL) after 24-48 h, while the hydrocortisone-NFs had a cell viability of around 93.2 to 82.3%. Our findings suggest that CS-g-PNVCL-coated Fe3O4@SiO2 NPs effectively enhance the solubility, loading capacity, and targeted delivery of poorly soluble drugs, thereby improving their therapeutic efficacy and bioavailability.

Synthesis and characterization of chitosan/collagen/polycaprolactone hydrogel films with enhanced biocompatibility and hydrophilicity for artificial tendon applications.

Regenerative medicine confronts various obstacles, such as creating and advancing biomaterials. Besides being safe, such materials should promote cellular activity. Polycaprolactone (PCL) has numerous medical applications as an engineering material. However, these polymers lack hydrophilicity. Herein, chitosan (CS)/collagen (COL)/polycaprolactone hydrogel films (CSCPs) were synthesized with different weight ratios of PCL; specifically, CS/COL (CSC): PCL content of 1:3, 1:6, and 1:9. For this purpose, novel COL immobilization on CS was performed via covalent attachment. Following the addition of PCL to CSC hydrogel, the resulting CSCP hydrogel films were characterized using tensile measurements, TGA, XRD, FTIR, and FE-SEM. A greater PCL content increases the elongation at break from 134.8 to 369.5 % and the tensile strength of the hydrogel films from 4.8 to 18.4 MPa. The hydrophobicity of prepared specimens was assessed through water absorption and contact-angle tests. For CSCP3 to CSCP9, the water contact angle increased from 61.03° to 70.82°. After 48 days, CSCP6 and CSCP9 hydrogel films demonstrated a slow rate of degradation, losing <15 % of their weight. Moreover, all three types of hydrogel films exhibited high biocompatibility (higher than 95 % after three days), as confirmed by the MTT assay. The hemolysis rates of CSCP hydrogel films were <2 %, which could be deemed safe for contact with a blood environment. The presence of no costly and bio-based crosslinking agents and desired characteristics for tissue engineering applications suggest that CSCP hydrogel films may be promising candidates for use in artificial tendons.

Self-Assembling Polymers with p-Aminosalicylate Anions Supported by Encapsulation of p-Aminosalicylate for the Improvement of Drug Content and Release Efficiency.

Bioactive linear choline-based copolymers were developed as micellar carriers for drug delivery systems (DDSs). The polymethacrylates containing trimethylammonium groups with p-aminosalicylate anions (PAS-based copolymers: series 1) or chloride anions (Cl-based copolymers: series 2) differing in ionic content and chain length were selected for drug loading. The diverse structures of amphiphilic copolymers made it possible to adjust the encapsulation efficiency of a well-known antibiotic, i.e., p-aminosalicylate in the form of sodium salt (PASNa) or acid (PASA), providing single drug systems. Goniometry was applied to verify the self-assembly capacity of the copolymers using the critical micelle concentration (CMC = 0.03-0.18 mg/mL) and the hydrophilicity level quantifying the surface wettability of polymer film using the water contact angle (WCA = 30-53°). Both parameters were regulated by the copolymer composition, indicating that the increase in ionic content caused higher CMC and lower WCA, but the latter was also modified to a less hydrophilic surface by drug encapsulation. The drug content (DC) in the PAS-based polymers was increased twice by encapsulation of PASNa and PASA (47-96% and 86-104%), whereas in the chloride-based polymer systems, the drug was loaded in 43-96% and 73-100%, respectively. Efficient drug release was detected for PASNa (80-100% series 1; 50-100% series 2) and PASA as complete in both series. The strategy of loading extra drug by encapsulation, which enhances the drug content in the copolymers containing anions of the same pharmaceutics, provided promising characteristics, which highlight the potential of PAS-loaded micellar copolymers for drug delivery.

pH-sensitive bilayer electrospun nanofibers based on ethyl cellulose and Eudragit S-100 as a dual delivery system for treatment of the burn wounds; preparation, characterizations, and in-vitro/in-vivo assessment.

A pH-sensitive bilayer electrospun nanofibrous mat containing both antibiotic (gentamicin sulfate, GEN) and non-steroidal anti-inflammatory (diclofenac sodium, DIC) drugs was fabricated for burn wound dressing by electrospinning technique, in which ethyl cellulose (EC) and ethyl cellulose/Eudragit S-100 (EC/ES-100) formed the top and bottom layers, respectively. The fabricated pH-sensitive bilayer electrospun nanofibrous mats were characterized from aspects of both structure and efficiency. Physicochemical properties were investigated via SEM, FTIR, and TGA. The swelling ratio and in vitro drug release of the fabricated nanofibrous mats were studied in different pHs. MTT was applied to assess the safety of the fiber mats. Finally, the in vivo efficiency of the designed pH-sensitive bilayer electrospun nanofibrous mats was examined on the male Wistar rats. Based on the histological analysis and wound healing test (in vivo animal experiments), the (ES100/EC-DIC/GEN)-(EC) pH-sensitive bilayer nanofibrous mat displayed faster wound healing than other bilayer nanofibrous mat. As a result, (ES100/EC-DIC/GEN)-(EC) bilayer nanofibrous mat with pH-responsion could accelerate the burn wound healing process via decreasing the adverse effects of GEN and DIC as topical antimicrobial and anti-inflammatory agents, receptively.

Synthesis and Characterization of Linear Copolymers Based on Pharmaceutically Functionalized Monomeric Choline Ionic Liquid for Delivery of p-Aminosalicylate.

Bioactive linear poly(ionic liquid)s (PIL) were designed as carriers in drug delivery systems (DDS). Their synthesis was based on a monomeric ionic liquid (MIL) with a relevant pharmaceutical anion to create therapeutically functionalized monomers, which further can be used in the controlled atom transfer radical polymerization (ATRP). The presence of chloride counterions in the quaternary ammonium groups of choline MIL, e.g., [2-(methacryloyloxy)ethyl]trimethyl-ammonium chloride (ChMACl), was stimulated to undergo the anion exchange with p-aminosalicylate sodium salt (NaPAS) as the source of the pharmaceutical anion with antibacterial activity. The resultant [2-(methacryloyloxy)ethyl]trimethylammonium p-aminosalicylate (ChMAPAS) was copolymerized to attain the well-defined linear choline-based copolymers with various contents of PAS anions (24-42%), which were regulated by the initial ratio of ChMAPAS to MMA and conversion degree. The length of polymeric chains was evaluated by the total monomer conversion (31-66%) yielding degree of polymerization (DPn = 133-272). Depending on the polymer carrier composition, PAS anions were exchanged by 60-100% within 1 h, 80-100% within 4 h, and completely after 24 h by phosphate anions in PBS imitating a physiological fluid.

Dual drug delivery system based on layered double hydroxides/carboxymethyl cellulose-poly ethylene oxide bionanocomposite electrospun fibrous mats: Fabrication, characterization, in-vitro and in-vivo studies.

The main goal of the present project was to design and develop ibuprofen (IBU) and layered double hydroxides-vancomycin (LDH-VAN) nanohybrid loaded bionanocomposite fibrous mats to increase the wound healing rate. Thus, first, LDH-VAN nanohybrid particles was synthesized by in-situ incorporation of VAN into the Mg-Al-LDH interlayers during the co-precipitation of hydroxides. Then, LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats were fabricated by electrospinning technique. Test samples were examined XRD, SEM, TEM, TGA, and FTIR. In vitro drug release test was performed in the phosphate buffer solution (pH = 7.4) to prove the efficiency of the fabricated bionanocomposite fibrous mats as a sustained-release carrier for both VAN and IBU. All the fabricated bionanocomposite fibrous mats did not displayed any significant cytotoxicity on NIH/3 T3 fibroblast cells. The wound area in the rats treated with LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats was less than other treatment groups. Based on histological analysis, the LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats possess a faster wound healing than other nanofibrous mats. Data obtained from the present project indicated that LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats could accelerate the wound healing process.