Publications

"Vision loss is a major complication in common ocular infections and diseases such as bacterial keratitis, age-related macular degeneration (AMD) and diabetic retinopathy (DR). The prevalence of such ophthalmic diseases represents an urgent need to develop safe, effective, and long-term treatments. Current therapies are riddled with drawbacks and limitations which calls for the exploration of alternative drug delivery mechanisms. Toxicity of the inorganic metals and metal oxides used for drug delivery raise safety concerns that are alleviated with the alternate use of, a natural and organic polymer which is both biocompatible and environmentally friendly. Carbon dots (CDs) represent a great potential in novel biomedical applications due to their tunable fluorescence, biocompatibility, and ability to be conjugated with diverse therapeutic materials. There is a growing interest on the exploitation of these properties for drug delivery with enhanced bio-imaging. However, there are limited reports of CD applications for ophthalmic indications. In this review, we focus on the CD potential and the development of translational therapies for ophthalmic diseases. The current review presents better understanding of fabrication of CDs and how it may be useful in delivering anti-bacterial agents, anti-VEGF molecules as well as imaging for ophthalmic applications."

"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 $\pm$ 8 to 355 $\pm$ 11 mg/g HA particles for vancomycin. The amounts of vancomycin and ciprofloxacin that were released linearly was estimated as 64.35 $\pm$ 7.35 and 25.00 $\pm$ 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."

"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 $\pm$ 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 $\pm$ 0.1 $μ$mol 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 $μ$g/mL."

"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 $\pm$ 1 to 99 $\pm$ 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 $\pm$ 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 $\pm$ 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."

"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% ($łeq$10%) crosslinker ratio were found to be mesoporous and provided the highest surface area, calculated as 21.54$\pm$10.31 m2/g for 2.5% crosslinked HA particles via BET analysis. Hydrolytic degradation of 2.5% crosslinked HA microparticles in PBS (pH 7.4) and at 37.5 ºC revealed a linear weight loss up to 20 days and 94.5$\pm$4.5% weight loss for 30 days was attained. A wide spectrum antibiotic, Vancomycin as a model drug was loaded to mesoporous HA particles via directly loading from aqueous corresponding solution and by chemical conjugation method to obtain controllable and sustained release profiles from HA particles. Up to 168 h linear vancomycin release (50.5$\pm$4.2 mg/g) was accomplished from 2.5% DVS crosslinked HA particles."

"HYPOTHESIS: Lactose (LAC) is a primary carbohydrate and energy source of milk has received intensive attention due to its unique functional and nutritional properties. Many biological beneficences of LAC make it an appealing molecule to seek for designing functional interfaces. Therefore, crosslinked poly(lactose) (p(LAC)) microgel from lactose disaccharides for potential biomedical applications was pursued as biocolloids for the first time. EXPERIMENT: p(LAC) microgels prepared by chemical crosslinking with DiVinyl Sulfone (DVS) were chemically modified with ethylenediamine (EDA) to obtain amine-modified p(LAC) (p(LAC)-EDA) microgels to induce new functionalities and properties. Blood compatibilities of bare p(LAC)-EDA microgels were tested through hemolysis and blood clotting tests. Rosmarinic acid (RA) used as a model drug was loaded into p(LAC) and p(LAC)-EDA microgels to demonstrate their applicability to be used in drug loading and release applications. FINDINGS: A facile preparation of p(LAC) microgels with high yield, 90 $\pm$ 5% and 0.5-50 µm size range was accomplished via water-in-oil (w/o) microemulsion crosslinking method. Upon chemical modification, the isoelectric point (IEP) from pH 1.8 for p(LAC) microgels changed to pH 7.7 for p(LAC)-EDA microgels, and the blood compatibility studies revealed that both microgels can be considered as blood compatible up to 2 mg/mL concentration, and only slight decrease in blood clotting index (BCI) of p(LAC)-EDA microgels was observed. Rosmarinic Acid (RA) was demonstrated to be released up to 4 days in phosphate buffer saline (PBS) with a linear release profile for p(LAC)-EDA microgels."

"Poly(hyaluronic acid) (p(HA)) particles with sizes from few hundred nm to few tens of micrometer were synthesized by using epoxy groups containing crosslinker glycerol diglycidyl ether (GDE) with high yield, 94$\pm$5%. P(HA) particles were oxidized by treatment with sodium periodate and then reacted with cationic polyethyleneimine (PEI) at 1:0.5, 1:1, and 1:2 wt ratio of p(HA):PEI to obtain p(HA)-PEI particles. From zeta potential measurements, isoelectronic points of bare p(HA) particles increased to pH 8.7 from 2.7 after modification with cationic PEI. New properties, such as antibacterial property, were attained for p(HA)-PEI after modification. The highest minimum bactericidal concentration (MBC) values were 0.5, 1, and 0.5mg/mL against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis species for 1:0.5 ratio of p(HA)-PEI at 72h incubation time. Moreover, the p(HA)-PEI particles were found to be biocompatible with L929 fibroblast cells, and interestingly, p(HA)-PEI particles were found to inhibit MDA-MB-231 breast and H1299 cancer cell growth depending on amount of PEI in p(HA)-PEI particles."

"OBJECTIVE: To create and test a slow-release antifibrotic drug-coated glaucoma drainage device using in vitro and in vivo experiments. METHODS: A slow-release device incorporating mitomycin C in poly(2-hydroxyethyl methacrylate) disks was developed using redox-polymerization techniques. A standardized preparation of this drug delivery device was attached to the Ahmed glaucoma valve (model FP7; New World Medical, Inc, Rancho Cucamonga, California). Semicircular disks (5 x 6 mm) of P(HEMA)-mitomycin C containing varying concentrations of mitomycin C per gram dry weight of the gel were attached to the lower half of an Ahmed glaucoma valve plate. Water was pumped through the modified Ahmed glaucoma valve at a rate comparable to that of aqueous humor outflow, and mitomycin C release was measured. Modified and unmodified Ahmed glaucoma valves were implanted in a rabbit model, and drug release and fibrosis were assessed after 3 months. RESULTS: The P(HEMA)-mitomycin C device released mitomycin C in vitro over 1 to 2 weeks. Studies in rabbits revealed that mitomycin C was released from the disks during the 3-month implantation. Histologic analysis demonstrated a significant reduction in inflammatory reaction and fibrosis in the resulting blebs. CONCLUSION: Our slow-release drug-coated glaucoma drainage device decreased fibrosis and inflammation in the resulting bleb in a rabbit model. CLINICAL RELEVANCE: This device could reduce the failure rate of glaucoma drainage devices."

"Glaucoma drainage devices (GDDs) create an alternate aqueous pathway by channeling aqueous from the anterior chamber through a long tube to an equatorial plate, inserted under the conjunctiva, which promotes bleb formation. GDDs are being used more frequently in the treatment of glaucoma, both as the primary procedure of choice and following failure of trabeculectomy operations. This article outlines the current concepts involving different GDDs, surgical techniques and a review of the current literature. In addition, the importance of the biomaterial and its implications for the success of the operation are discussed."