Ophthalmic drug delivery system based on the complex of gellan and ofloxacin

Complex formation between a natural polysaccharide – gellan and an antimicrobial drug – ofloxacin was studied in aqueous solution. Conductimetric and potentiometric titration curves revealed that gellan and ofloxacin forms a water-soluble complex of composition 2:1 mol/mol stabilized by ionic and hydrogen bonds. The formation of the gellan-ofloxacin complex was confirmed by FTIR spectroscopy, dynamic light scattering, zeta-potential and thermogravimetric analysis. The average hydrodynamic size of the complex was found 307±5 nm and its zetapotential was negative and equal to -15 mV. Thin films of the gellan-ofloxacin complex, gelled in 0.3 wt.% of CaCl2, were used to study the release kinetics of ofloxacin in distilled water and phosphate buffer. The drug release kinetics evaluated by UV-Vis spectroscopy at λmax = 289 nm and calculated by the Ritger-Peppas model correspond to non-Fickian diffusion in distilled water and Case II transport (zero-order kinetics) in phosphate buffer. The cumulative release of ofloxacin from the gellan-ofloxacin films was equal to 96±2% and 36±2% in phosphate buffer and distilled water, respectively. It is expected that the gellan-ofloxacin complex is able to form in situ gel on the surface of the eye and to prolong the drug residence time in the tear fluid.Peer reviewe

Poly(2-ethyl-2-oxazoline) grafted gellan gum for potential application in transmucosal drug delivery

Gellan gum (GG) has been used to prepare polymeric carriers with prolonged retention on the eye surface for topical ocular drug delivery. In this work, GG was chemically modified with short poly(2-ethyl-2-oxazoline) (PEtOx) chains that were expected to have minimal adhesion to mucosal tissues (mucoadhesion). The choice of synthetic procedure, solvents, and reagents has been dictated by biocompatibility of the materials and possible application in drug delivery. The grafts were synthesized via cationic ring-opening polymerization and their living chains were attached onto deprotonated gellan backbone. The derivatives with three degrees of grafting were prepared by varying the in-feed mass ratio of PEtOx grafts over GG. NMR and FT-IR spectroscopies, thermogravimetric analysis, and SEC evidenced that the grafting had actually taken place. However, a greater diffusion coefficient determined for the copolymer, using diffusion-ordered spectroscopy (NMR), in relation to the diffusion of the unmodified GG, suggested either partial degradation of the backbone or a more compact structure of the copolymer. GG and its graft copolymers (GG-g-PEtOx) were found to be highly biocompatible with cells cultured under their induction at concentration of 1, 0.1 and 0.01 mg/mL demonstrated a physiological morphology, as well as an increase in viability and proliferation.Peer reviewe

Photo- and Acid-Degradable Polyacylhydrazone–Doxorubicin Conjugates

Light-mediated polymer degradation has attracted considerable attention in various applications, including photo-patterning, tissue engineering and photo-triggered drug delivery. In this study, we report the synthesis and characterization of a new, linear, main-chain photo- and acid-degradable copolymer based on acylhydrazone linkages. The polymer was synthesized via a step-growth copolymerization of adipic acid dihydrazide with a bifunctional poly(ethylene glycol) bearing benzaldehyde end-groups, under mild acidic conditions, to afford a hydrophilic PEG-alt-adipic acid (PEG-alt-AA) alternating copolymer. The synthesized polymer was characterized by size exclusion chromatography, proton nuclear magnetic resonance and attenuated total reflection-Fourier transform infrared spectroscopies. The main-chain photo- and acid-induced degradation of the copolymer in dimethylsulfoxide and water, respectively, was verified by UV-vis spectroscopy at light intensities as low as 0.1 mW cm−2 at λ = 254 nm. Next, a model anticancer drug, doxorubicin (DOX), was chemically linked to the polymer chain end(s) via acylhydrazone bond(s), resulting in amphiphilic PEG-alt-adipic acid-DOX (PEG-alt-AA-DOX) polymer–drug conjugates. The conjugates were self-assembled in water to form spherical nanoparticles, as evidenced by scanning and transmission electron microscopies. The irradiation of the self-assembled PEG-alt-AA-DOX conjugates with UV light and the decrease of the solution pH resulted in the disruption of the assemblies due to the photolysis and acidolysis of the acylhydrazone bonds, and the release of the therapeutic cargo

Osteogenic Potential of Pre-Osteoblastic Cells on a Chitosan-graft-Polycaprolactone Copolymer

A chitosan-graft-polycaprolactone (CS-g-PCL) copolymer synthesized via a multi-step process was evaluated as a potential biomaterial for the adhesion and growth of MC3T3-E1 pre-osteoblastic cells. A strong adhesion of the MC3T3-E1 cells with a characteristic spindle-shaped morphology was observed from the first days of cell culture onto the copolymer surfaces. The viability and proliferation of the cells on the CS-g-PCL surfaces, after 3 and 7 days in culture, were significantly higher compared to the cells cultured on the tissue culture treated polystyrene (TCPS) control. The osteogenic potential of the pre-osteoblastic cells cultured on CS-g-PCL surfaces was evaluated by determining various osteogenic differentiation markers and was compared to the TCPS control surface. Specifically, alkaline phosphatase activity levels show significantly higher values at both time points compared to TCPS, while secreted collagen into the extracellular matrix was found to be higher on day 7. Calcium biomineralization deposited into the matrix is significantly higher for the CS-g-PCL copolymer after 14 days in culture, while the levels of intracellular osteopontin were significantly higher on the CS-g-PCL surfaces compared to TCPS. The enhanced osteogenic response of the MC3T3-E1 pre-osteoblasts cultured on CS-g-PCL reveals that the copolymer underpins the cell functions towards bone tissue formation and is thus an attractive candidate for use in bone tissue engineering

Stimuli-Responsive Polysaccharide Hydrogels and Their Composites for Wound Healing Applications

There is a growing concern about wound care, since traditional dressings such as bandages and sutures can no longer meet existing needs. To address the demanding requirements, naturally occurring polymers have been extensively exploited for use in modern wound management. Polysaccharides, being the most abundant biopolymers, have some distinct characteristics, including biocompatibility and biodegradability, which render them ideal candidates for wound healing applications. Combining them with inorganic and organic moieties can produce effective multifunctional composites with the desired mechanical properties, high wound healing efficiencies and excellent antibacterial behavior. Recent research endeavors focus on the development of stimuli-responsive polysaccharide composites for biomedical applications. Polysaccharide composites, being sensitive to the local environment, such as changes of the solution temperature, pH, etc., can sense and react to the wound conditions, thus promoting an effective interaction with the wound. This review highlights the recent advances in stimuli-responsive polysaccharide hydrogels and their composites for use in wound healing applications. The synthetic approaches, physical, chemical, and biochemical properties as well as their function in wound healing will be discussed

Responsive Quaternized PDMAEMA Copolymers with Antimicrobial Action

In this work, the antimicrobial action of partially quaternized poly(2-(dimethylamino)ethyl methacrylate) (PQDMAEMA) copolymers using different alkyl halides is presented. The poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) homopolymer was synthesized by group transfer polymerization, followed by the modification of its tertiary amine groups, using bromoethane, iodoethane, bromohexane and bromoethanol, to introduce permanent cationic, quaternary ammonium salt moieties, randomly distributed along the polymer chains. In all cases, the degree of quaternization was low, at ~10 mol%, as verified by proton nuclear magnetic resonance spectroscopy to preserve the thermo-responsive character of the PDMAEMA precursor polymer. The biocidal activity of the lightly quaternized PQDMAEMA copolymers against Escherichia coli and Staphylococcus aureus was evaluated by calculating the minimum inhibitory concentration (MIC) as well as the minimum bactericidal concentration (MBC) of the polymers and by comparing them to the respective values of the precursor non-quaternized PDMAEMA homopolymer. The antibacterial mechanism of action in the solution was studied by zeta potential measurements, scanning electron microscopy and protein leakage tests signifying the disruption of the outer membrane of the bacterial cells to release their periplasmic proteins