Drug-impregnated contact lenses via supercritical carbon dioxide: A viable solution for the treatment of bacterial and fungal keratitis.

Keratitis is a corneal infection caused by various bacteria and fungi. Eye drop treatment of keratitis involves significant challenges due to difficulties in administration, inefficiencies in therapeutic dosage, and frequency of drug applications. All these are troublesome and result in unsuccessful treatment, high cost, time loss, development of drug resistance by microorganisms, and a massive burden on human health and the healthcare system. Most of the antibacterial and antifungal medications are non-water-soluble and/or include toxic drug formulations. Here, the aim was to develop drug-loaded contact lenses with therapeutic dosage formulations and extended drug release capability as an alternative to eye drops, by employing supercritical carbon dioxide (ScCO2) as a drug impregnation solvent to overcome inefficient ophthalmic drug use. ScCO2, known as a green solvent, has very low viscosity which provides high mass transfer power and could enhance drug penetration into contact lenses much better with respect to drug loading using other solvents. Here, moxifloxacin (MOX) antibiotic and amphotericin B (AMB) antifungal medicines were separately loaded into commercially available silicone hydrogel contact lenses through 1) drug adsorption from the aqueous solutions and 2) impregnation techniques via ScCO2 and their efficacies were compared. Drug impregnation parameters, i.e., 8-25 MPa pressure, 310-320 K temperature, 2-16-hour impregnation times, and the presence of ethanol as polar co-solvent were investigated for the optimization of the ScCO2 drug impregnation process. The highest drug loading and long-term release kinetic from the contact lenses were obtained at 25 MPa and 313 K with 2.5 h impregnation time by using 1 % ethanol (by volume). Furthermore, antibacterial/antifungal activities of the MOX- and AMB-impregnated contact lenses were effective against in vitro Pseudomonas aeruginosa (ATCC 10145) bacteria and Fusarium solani (ATCC 36031) fungus for up to one week. Consequently, the ScCO2 method can be effectively used to impregnate commercial contact lenses with drugs, and these can then be safely used for the treatment of keratitis. This offers a sustainable delivery system at effective dosage formulations with complete bacterial/fungal inhibition and termination, making it viable for real animal/human applications.

Fluorescent Graphitic Carbon Nitride (g-C3N4)-Embedded Hyaluronic Acid Microgel Composites for Bioimaging and Cancer-Cell Targetability as Viable Theragnostic.

Fluorescent graphitic carbon nitride (g-C3N4) doped with various heteroatoms, such as B, P, and S, named Bg-C3N4, Pg-C3N4, and Sg-C3N4, were synthesized with variable band-gap values as diagnostic materials. Furthermore, they were embedded within hyaluronic acid (HA) microgels as g-C3N4@HA microgel composites. The g-C3N4@HA microgels had a 0.5-20 µm size range that is suitable for intravenous administration. Bare g-C3N4 showed excellent fluorescence ability with 360 nm excitation wavelength and 410-460 emission wavelengths for possible cell imaging application of g-C3N4@HA microgel composites as diagnostic agents. The g-C3N4@HA-based microgels were non-hemolytic, and no clotting effects on blood cells or cell toxicity on fibroblasts were observed at 1000 µg/mL concentration. In addition, approximately 70% cell viability for SKMEL-30 melanoma cells was seen with Sg-C3N4 and its HA microgel composites. The prepared g-C3N4@HA and Sg-C3N4@HA microgels were used in cell imaging because of their excellent penetration capability for healthy fibroblasts. Furthermore, g-C3N4-based materials did not interact with malignant cells, but their HA microgel composites had significant penetration capability linked to the binding function of HA with the cancerous cells. Flow cytometry analysis revealed that g-C3N4 and g-C3N4@HA microgel composites did not interfere with the viability of healthy fibroblast cells and provided fluorescence imaging without any staining while significantly decreasing the viability of cancerous cells. Overall, heteroatom-doped g-C3N4@HA microgel composites, especially Sg-C3N4@HA microgels, can be safely used as multifunctional theragnostic agents for both diagnostic as well as target and treatment purposes in cancer therapy because of their fluorescent nature.

Rapid Pathogen Purge by Photosensitive Arginine-Riboflavin Carbon Dots without Toxicity.

Photo-activatable antipathogenic carbon dots (CDs) were prepared by carbonization of citric acid and arginine (Arg) via 3 min microwave treatment for use in the eradication of common microorganisms. Nitrogen-doped Arg CDs were spherical in shape with a size range of 0.5 to 5 nm. The Arg CDs were modified with fluorescent dyes, such as fluorescein sodium salt (FSS, as Arg-FSS) and riboflavin (RBF, as Arg-RBF), to improve antimicrobial potency by enhancing their application in photodynamic therapy. The modified Arg CDs afforded fluorescence emission properties at 520 nm in the green region in addition to excellent blue fluorescence intensity at 420 nm under 345 nm excitation upon their FSS and RBF conjugation, respectively. Although the cytotoxicity of Arg CDs was decreased for Arg-RBF CDs to 91.2 ± 0.7% cell viability for fibroblasts, the Arg-based CDs could be safely used for intravenous applications at 1000 µg/mL concentration. The Arg CDs showed broad-spectrum antimicrobial activity against common pathogens and the minimum inhibitory concentration of Arg CDs was almost two-fold decreased for the modified forms without UV light. However, faster and more effective antibacterial activity was determined for photosensitive Arg-RBF CDs, with total bacterial eradication upon UV-A light exposure for 30 min.

Physically Crosslinked Chondroitin Sulfate (CS)-Metal Ion (M: Fe(III), Gd(III), Zn(II), and Cu(II)) Particles for Versatile Applications and Their Biosafety.

Chondroitin sulfate (CS), a well-known glycosaminoglycan, was physically crosslinked with Fe(III), Gd(III), Zn(II), and Cu(II) ions to obtain CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) polymeric particles for multipurpose biological applications. The CS-metal ion-containing particles in the micrometer to a few hundred nanometer size range are injectable materials for intravenous administration. The CS-metal ion-containing particles are safe biomaterials for biological applications because of their perfect blood compatibility and no significant cytotoxicity on L929 fibroblast cells up to a 10 mg/mL concentration. Furthermore, CS-Zn(II) and CS-Cu(II) particles show excellent antibacterial susceptibility, with 2.5-5.0 mg/mL minimum inhibition concentration (MIC) values against Escherichia coli and Staphylococcus aureus. Moreover, the in vitro contrast enhancement abilities of aqueous CS-metal ion particle suspensions in magnetic resonance imaging (MRI) were determined by obtaining T1- and T2-weighted MR images using a 0.5 Tesla MRI scanner and by calculating the water proton relaxivities. Therefore, these CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) particles have significant potential as antibacterial additive materials and MRI contrast enhancement agents with less toxicity.

Nontoxic Natural Polymeric Particle Vehicles Derived from Hyaluronic Acid and Mannitol as Mitomycin C Carriers for Bladder Cancer Treatment.

Hyaluronic acid/mannitol (HA/MN)-based particles were designed as mitomycin c (MMC) delivery vehicles through the crosslinking of 1:0, 3:1, 1:3, and 0:1 mole ratios of HA/MN to investigate their potential use in bladder cancer therapy. The HA/MN-MMC particles prepared by the microemulsion crosslinking method were of 0.5-10 µm size with a zeta potential value of -36.7 mV. The MMC carrier potential of the HA/MN-MMC particles was investigated by changing HA/MN ratios in the particle structure. The MMC loading capacity of neat HA particles was 5.3 ± 1.1 mg/g, whereas HA/MN (1:3) particles could be loaded with about three times more drug, for example, 18.4 ± 0.8 mg/g. The kinetic of MMC drug delivery from the HA/MN-MMC particles were tested in vitro in bladder cancer conditions for example, pH 4.5, 6, and 7.4. The HA-MMC particles released approximately 70% of the loaded drug in 300 h, while 43% of the loaded drug was released from the HA/MN-MMC particles within 600 h under physiological conditions, pH 7.4, 37 °C. The cytotoxicity of HA-based particles on healthy L929 fibroblast cells and HTB-9 human bladder cancer cells was investigated in vitro via MTT tests. Bare MMC inhibited about 90% of L929 fibroblast cells even at 100 µg/mL, but the cell viabilities in the presence of HA-MMC and HA/MN-MMC particles were 85 ± 5 and 109 ± 7% at 1000 µg/mL, respectively. The HA/MN-MMC (1:3) particles at 1000 µg/mL were found capable of destroying half of HTB-9 human bladder cancer cells within 24 h. Interestingly, the same particles at 50 µg/mL destroyed almost all the cancer cells with 8 ± 5% cell viability in 72 h of incubation time. The designed HA/MN-MMC (1:3) particles were found to afford a chemotherapeutic effect on the tumor cancers while reducing the toxicity of MMC against L929 fibroblast cells.

Polyelectrolyte Chondroitin Sulfate Microgels as a Carrier Material for Rosmarinic Acid and Their Antioxidant Ability.

Polyelectrolyte microgels derived from natural sources such as chondroitin sulfate (CS) possess considerable interest as therapeutic carriers because of their ionic nature and controllable degradation capability in line with the extent of the used crosslinker for long-term drug delivery applications. In this study, chemically crosslinked CS microgels were synthesized in a single step and treated with an ammonia solution to attain polyelectrolyte CS-[NH4]+ microgels via a cation exchange reaction. The spherical and non-porous CS microgels were injectable and in the size range of a few hundred nanometers to tens of micrometers. The average size distribution of the CS microgels and their polyelectrolyte forms were not significantly affected by medium pH. It was determined that the -34 ± 4 mV zeta potential of the CS microgels was changed to -23 ± 3 mV for CS- [NH4]+ microgels with pH 7 medium. No important toxicity was determined on L929 fibroblast cells, with 76 ± 1% viability in the presence of 1000 µg/mL concentration of CS-[NH4]+ microgels. Furthermore, these microgels were used as a drug carrier material for rosmarinic acid (RA) active agent. The RA-loading capacity was about 2.5-fold increased for CS-[R]+ microgels with 32.4 ± 5.1 µg/mg RA loading, and 23% of the loaded RA was sustainably release for a long-term period within 150 h in comparison to CS microgels. Moreover, RA-loaded CS-[R]+ microgels exhibited great antioxidant activity, with 0.45 ± 0.02 µmol/g Trolox equivalent antioxidant capacity in comparison to no antioxidant properties for bare CS particles.

Degradable and Non-Degradable Chondroitin Sulfate Particles with the Controlled Antibiotic Release for Bacterial Infections.

Non-degradable, slightly degradable, and completely degradable micro/nanoparticles derived from chondroitin sulfate (CS) were synthesized through crosslinking reactions at 50%, 40%, and 20% mole ratios, respectively. The CS particles with a 20% crosslinking ratio show total degradation within 48 h, whereas 50% CS particles were highly stable for up to 240 h with only 7.0 ± 2.8% weight loss in physiological conditions (pH 7.4, 37 °C). Tobramycin and amikacin antibiotics were encapsulated into non-degradable CS particles with high loading at 250 g/mg for the treatment of corneal bacterial ulcers. The highest release capacity of 92 ± 2% was obtained for CS-Amikacin particles with sustainable and long-term release profiles. The antibacterial effects of CS particles loaded with 2.5 mg of antibiotic continued to render a prolonged release time of 240 h with 24 ± 2 mm inhibition zones against Pseudomonas aeruginosa. Furthermore, as a carrier, CS particles significantly improved the compatibility of the antibiotics even at high particle concentrations of 1000 g/mL with a minimum of 71 ± 7% fibroblast cell viability. In summary, the sustainable delivery of antibiotics and long-term treatment of bacterial keratitis were shown to be afforded by the design of tunable degradation ability of CS particles with improved biocompatibility for the encapsulated drugs.

Thiourea-Isocyanate-Based Covalent Organic Frameworks with Tunable Surface Charge and Surface Area for Methylene Blue and Methyl Orange Removal from Aqueous Media.

A thiourea hexamethylene diisocyanate covalent organic framework (TH COF) was synthesized by adjusting the surface charge and surface area. The surface charge value of TH COF, −3.8 ± 0.5 mV, can be changed to −29.1 ± 0.4 mV by treatment with NaOH (dp-TH) and 17.1 ± 1.0 mV by treatment with HCl (p-TH). Additionally, the surface area of TH COF was 39.3 m2/g, whereas the surface area of dp-TH COF and p-TH COF structures were measured as 41.4 m2/g and 42.5 m2/g, respectively. However, the COF structure had a better adsorption capability with acid and base treatments, e.g., dp-TH COF absorbed 5.5 ± 0.3 mg/g methylene blue (MB) dye, and p-TH COF absorbed 25.9 ± 1.4 mg/g methyl orange (MO) dye from 100 mL 25 ppm aqueous dye solutions, thereby increasing the MB and MO absorption amounts of the TH COF structure. Furthermore, by calculating the distribution, selectivity, and relative selectivity coefficients, the absorption capacity order was determined as dp-TH > TH > p-TH COFs for the MB dye, whereas it was p-TH > TH > dp-TH COFs for the MO dye. Finally, the reusability of dp-TH COF for MB absorption and p-TH COF for MO absorption were investigated. After five repeated uses, dp-TH COF retained 64.6 ± 3.7% of its absorption ability, whereas p-TH COF preserved 79.7 ± 3.2% of its absorption ability relative to the initial absorption amount.

Titanium platelet-rich fibrin (T-PRF) as high-capacity doxycycline delivery system.

OBJECTIVES: Titanium platelet-rich fibrin (T-PRF), a second-generation autogenous blood concentrate with tough and thick fibrin meshwork activated by a titanium tube, was used as a drug carrier for doxycycline (Doxy) by injection. The objective of this study is to evaluate the loading capacity of T-PRF, release kinetics of doxycycline-loaded T-PRF, and its antibacterial effects against S. aureus and P. aeruginosa. MATERIALS AND METHODS: The T-PRF and collagen were loaded with Doxy as T-PRF/Doxy and Collagen/Doxy, and their release and antibacterial activities against S. aureus and P. aeruginosa were investigated. Chemical characterization and morphological analysis were performed. RESULTS: In comparison with collagen, approximately sevenfold more Doxy, 281 mg/g, was loaded into T-PRF. It was found that 25% of the loaded Doxy was released from T-PRF compared to only 12% from collagen within 72 h. The largest inhibition zone diameter (IZD) was observed for T-PRF/Dox with 32 ± 6 mm and 37 ± 5 mm for P. aereginosa and S. aureus, respectively. However, only 10 ± 5 mm and 10 ± 6 mm IZD were observed for bare T-PRF, and no inhibition zone was observed for the Collagen/Doxy group. A dense fibrin structure was visualized on SEM images of the T-PRF/Doxy group compared to the T-PRF group. CONCLUSIONS: T-PRF has higher Doxy loading capacity and long-acting antibacterial effects compared to collagen. T-PRF was shown to have potential autogenous long-term drug-carrying capability for doxycycline. Also, the potential fibrinophilic properties of Doxy were observed to strengthen the structure of T-PRF. CLINICAL RELEVANCE: T-PRF is an autogenous drug career with high loading capacity and extended antibacterial effects for doxycycline. Doxycycline molecules can be visible on T-PRF fibers. This study suggests that T-PRF/Dox could be used as a proper antibiotic delivery device in the treatments of periodontitis and peri-implantitis.

Biocompatible poly(galacturonic acid) micro/nanogels with controllable degradation via tunable chemical crosslinking.

Here, one-pot labor-less preparation of two different polygalacturonic acid (PGA) micro/nanogel formulations, PGA-1 and PGA-2, by respectively crosslinking the PGA chains with divinyl sulfone (DVS) and trimethylolpropane triglycidyl ether (TMPGDE) were reported. Various crosslinker ratios, 2.5, 10, 50, and 100% were used for both crosslinkers to demonstrate the tunability of their degradation properties. The PGA micro/nanogels were found spherical-shaped porous particles in 0.5-5.0 µm size range by SEM. The hydrolytic degradation and stability of PGA micro/nanogels in pH 1.0, 7.4, and 9.0 buffer solutions can be controlled by changing the degree of crosslinking. Accordingly, 32 ± 8% and 36 ± 2% weight losses were attained for PGA-1-10% and PGA-2-10% micro/nanogels at pH 1, respectively, and 46 ± 6%, and 68 ± 6% degradations were determined at pH 7.4 within 4 weeks. However, no degradation was observed for both PGA-based micro/nanogel formulations prepared at 25% and 100% crosslinker ratios at all pH conditions. All PGA-based micro/nanogels were totally degraded within 7-10 days at pH 9.0. In the presence of pectinase and amyloglucosidase enzymes, all formulations of PGA micro/nanogels showed more than 80% degradation within 12 h. Furthermore, both PGA formulations showed no significant cytotoxicity against L929 fibroblast cells with 90% and above cell viability up to 250 mg/mL concentrations.

Hyaluronic acid (HA)-Gd(III) and HA-Fe(III) microgels as MRI contrast enhancing agents.

Hyaluronic acid (HA) was crosslinked with Gd(III) and Fe(III) ions rendering physically crosslinked HA-metal(III) microgels as magnetic resonance imaging (MRI) enhancing contrast agents. These HA-Gd(III) and HA-Fe(III) microgels are injectable with size range, 50-5000 nm in water. The same isoelectric point, pH 1.2 ± 0.1, was measured for both microgels. HA-Gd(III) and HA-Fe(III) microgels are hemo-compatible biomaterials and can be safely used in intravascular applications up to 1000 µg/mL concentration. Furthermore, no significant toxicity was attained as 95 ± 8 and 81 ± 2% cell viability on L929 fibroblast cells at 100 µg/mL of HA-Gd(III) and HA-Fe(III) microgels were measured. Moreover, HA-Gd(III) microgels were found to afford significant contrast improvement capability in MRI with proton relaxivity, r1 = 2.11 mM-1 s-1, comparable with the values reported for Gd(III) labeled functionalized HA gel systems and commercial Gd based contrast agents.

Versatile Fluorescent Carbon Dots from Citric Acid and Cysteine with Antimicrobial, Anti-biofilm, Antioxidant, and AChE Enzyme Inhibition Capabilities.

Nanostructured fluorescent particles derived from natural molecules were prepared by a green synthesis technique employing a microwave method. The precursors citric acid (CA) and cysteine (Cys) were used in the preparation of S- and N-doped Cys carbon dots (Cys CDs). Synthesis was completed in 3 min. The graphitic structure revealed by XRD analysis of Cys CDs dots had good water dispersity, with diameters in the range of 2-20 nm determined by TEM analysis. The isoelectric point of the S, N-doped CDs was pH value for 5.2. The prepared Cys CDs displayed excellent fluorescence intensity with a high quantum yield of 75.6 ± 2.1%. Strong antimicrobial capability of Cys CDs was observed with 12.5 mg/mL minimum bactericidal concentration (MBC) against gram-positive and gram-negative bacteria with the highest antimicrobial activity obtained against Staphylococcus aureus. Furthermore, Cys CDs provided total biofilm eradication and inhibition abilities against Pseudomonas aeruginosa at 25 mg/mL concentration. Cys CDs are promising antioxidant materials with 1.3 ± 0.1 µmol Trolox equivalent/g antioxidant capacity. Finally, Cys CDs were also shown to inhibit the acetylcholinesterase (AChE) enzyme, which is used in the treatment of Alzheimer's disease, even at the low concentration of 100 µg/mL.

Antimicrobial activity and biocompatibility of slow-release hyaluronic acid-antibiotic conjugated particles.

Here, the aim was to design and use a long-lasting antibiotic release system for prevention of postoperative infections in ophthalmic surgery. Ciprofloxacin and vancomycin-conjugated hyaluronic acid (HA) particles were prepared as drug carriers for sustained release of antibiotics. The antimicrobial effects of the released drugs were determined by disc-diffusion and macro-dilution tests at different times up to 2 weeks. Slow degradable HA particles were obtained with 35.2 wt% degradation within 21 days. The drug loading amount was increased by employing two sequential chemical linking (conjugation, 2C) and one physical absorption loading (A) procedures (2C + A processes) from 148 ± 8 to 355 ± 11 mg/g HA particles for vancomycin. The amounts of vancomycin and ciprofloxacin that were released linearly was estimated as 64.35 ± 7.35 and 25.00 ± 0.68 mg/g, respectively, from drug-conjugated HA particles in 100 h. Antimicrobial studies revealed that antibiotic-conjugated HA particles could inhibit the growth of microorganisms from 1 h to 1 week. The MBC values were measured as 0.25, 4.0, and 0.25 mg/mL against Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis, respectively, after 72 h incubation time. Cytotoxicity studies showed no difference between fibroblast growth or corneal thickness after 5 days with or without HA-antibiotic particles. The drug release studies and antimicrobial activity of antibiotic-loaded HA particles with time against various bacteria further revealed that HA particles are very effective in preventing bacterial infections. Likewise, cytotoxicity studies suggest that these particles pose no toxicity to eukaryotic cells, including corneal endothelium.

Nitrogen and Sulfur Doped Carbon Dots from Amino Acids for Potential Biomedical Applications.

Nitrogen (N-) and sulfur (S-) doped carbon dots (CDs) were synthesized in a single step in a few min, 1-4 min via microwave technique from five different types of amino acids viz. Arginine (A), Lysine (L), Histidine (H), Cysteine (C), and Methionine (M). These amino acid derived N- and/or S- doped CDs were found to be in spherical shapes with 5-20 nm particle size range determined by Transition Electron Microscope (TEM) images and Dynamic Light Scattering (DLS) measurements. Thermal degradation, functional groups, and surface potential of the CDs were determined by Thermogravimetric Analysis (TGA), FT-IR spectroscopy, and zeta potential measurements, respectively. Although the zeta potential value of Cysteine derived CD (C-CD) was measured as -7.45±1.32 mV, the zeta potential values of A-CD, L-CD, H-CD, and M-CD particles were measured as +2.84±0.67, +2.61±1.0, +4.10±1.50 and+2.20±0.60 mV, respectively. Amongst the CDs, C- CDs was found to possess the highest quantum yield, 89%. Moreover, the blood compatibility test of CDs, determined with hemolysis and blood clotting tests was shown that CDs at 0.25 mg/mL concentration, CDs has less than 5% hemolysis ratio and higher than 50% blood clotting indexes. Furthermore, A-CD was modified with polyethyleneimine (PEI) and was found that the zeta potential values was increased to +34.41±4.17 mV (from +2.84±0.67 mV) inducing antimicrobial capability to these materials. Minimum Inhibition Concentration (MIC) of A-CD dots was found as 2.5 mg/mL whereas the PEI modified A-CDs, A-CD-PEI was found as 1 mg/mL against Escherichia coli ATCC 8739 (gram -) and Staphylococcus aureus ATCC 6538 (gram +) bacteria strains signifying the tunability of CDs.

Enhancement of biocompatibility and carbohydrate absorption control potential of rosmarinic acid through crosslinking into microparticles.

Rosmarinic acid (RA), a bioflavonoid and antioxidant that exists in plants of the Lamiaceae family, was crosslinked into particles as poly(Rosmarinic Acid) (p(RA)) via an emulsion crosslinking method. The particles were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, solid state nuclear magnetic resonance 13C NMR spectroscopy, and thermal gravimetric analysis. The zeta potential values of p(RA) particles were determined at different pHs; the isoelectric point was estimated as pH 1.2. The release of monomeric RA from the particles at 37.5 °C was found to be similar at different pHs, 1.0, 7.4, and 11.0. The effects of p(RA) on hemolysis and coagulation were found to be minimal. The antioxidant activity of p(RA) particles and RA monomer were almost indistinguishable suggesting that p(RA) particles may be used as an antioxidant. On a per weight basis, p(RA) particles were ~66% less cytotoxic to mammalian cells that RA monomer, as assessed using COS-1 cells. In addition, p(RA) was an 8.6-fold stronger inhibitor of α-glycosidase than RA; the IC50s of the monomer and particles were 0.121 and 0.014 mg/mL, respectively. The strong inhibitory effect of p(RA) on α-glycosidase, coupled with its reduced cytotoxicity and antioxidant activity, provide new opportunities for the use of p(RA).

Cryogel composites based on hyaluronic acid and halloysite nanotubes as scaffold for tissue engineering.

We present here preparation of mechanically strong and biocompatible cryogel composites based on hyaluronic acid (HA) and halloysite nanotubes (HNTs) of various compositions, and their applications as scaffold for different cell growing media. Uniaxial compression tests reveal that the incorporation of HNTs into HA cryogels leads to a ~2.5-fold increase in their Young moduli, e.g., from 38 ±â€¯1 to 99 ±â€¯4 kPa at a HA:HNTs weight ratio of 1:2. Although HA:HNTs based cryogels were found to be blood compatible with 1.37 ±â€¯0.11% hemolysis ratio at a HA:HNTs weight ratio of 1:2, they trigger thrombogenic activity with a blood clotting index of 17.3 ±â€¯4.8. Remarkably, HA:HNTs cryogel composites were found to be excellent scaffold materials in the proliferation of rat mesenchymal stem cells (MSC), human cervical carcinoma cells (HeLa), and human colon cancer cells (HCT116). The cell studies revealed that an increased amount of HNT embedding into HA cryogels leads to an increase of MSC proliferation.

Mesoporous, degradable hyaluronic acid microparticles for sustainable drug delivery application.

Porous and degradable hyaluronic acid (HA) microparticles was synthesized in a single step using different ratio of crosslinker, divinylsulfone (DVS) ranging between 2.5 and 100% mole ratio of HA repeating unit. HA particles less than 25% (≤10%) crosslinker ratio were found to be mesoporous and provided the highest surface area, calculated as 21.54±10.31 m2/g for 2.5% crosslinked HA particles via BET analysis. Hydrolytic degradation of 2.5% crosslinked HA microparticles in PBS (pH 7.4) and at 37.5 ºC revealed a linear weight loss up to 20 days and 94.5±4.5% weight loss for 30 days was attained. A wide spectrum antibiotic, Vancomycin as a model drug was loaded to mesoporous HA particles via directly loading from aqueous corresponding solution and by chemical conjugation method to obtain controllable and sustained release profiles from HA particles. Up to 168 h linear vancomycin release (50.5±4.2 mg/g) was accomplished from 2.5% DVS crosslinked HA particles.