A5087138805- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Glaucoma and retinal disorders
- Retinoids in leukemia and cellular processes
- Biotin and Related Studies
- Ocular Diseases and Behçet’s Syndrome
- Cell Adhesion Molecules Research
- Folate and B Vitamins Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Advanced Drug Delivery Systems
- Adenosine and Purinergic Signaling
- Growth Hormone and Insulin-like Growth Factors
- Vitamin D Research Studies
- Drug Transport and Resistance Mechanisms
- Neonatal Health and Biochemistry
- Complement system in diseases
- Retinal and Optic Conditions
- Click Chemistry and Applications
- Antibiotics Pharmacokinetics and Efficacy
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Facial Rejuvenation and Surgery Techniques
- Retinal and Macular Surgery
- Proteins in Food Systems
- HIV/AIDS drug development and treatment
Clearside Biomedical (United States)
2019-2022
Novartis (United States)
2012-2018
Boston Biomedical Research Institute
2018
Novartis (Switzerland)
2015
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010
University of Missouri–Kansas City
2005-2010
Abstract Protein drugs that neutralize vascular endothelial growth factor (VEGF), such as aflibercept or ranibizumab, rescue vision in patients with retinal diseases. Nonetheless, optimal visual outcomes require intraocular injections frequently every month. Here we report a method to extend the intravitreal half-life of protein an alternative either encapsulation chemical modifications polymers. We combine 97-amino-acid peptide human origin binds hyaluronan, major macromolecular component...
Purpose: To compare ocular pharmacokinetics (PK), systemic absorption, and injectability of triamcinolone acetonide (TA) suprachoroidal (SC) intravitreal (IVT) suspensions. Methods: New Zealand White (NZW) rabbits received a bilateral injection 4 mg TA injectable suspension, TRI (TRIESENCE ®; Alcon) through either microneedle-based SC or standard IVT injection. Another group NZW (4 mg) proprietary suspension for use, CLS-TA (Clearside Biomedical). Blood tissues were analyzed over 3 months....
The objective of this research is to characterize a sodium-dependent multivitamin transporter (SMVT) in MDCK-MDR1 cells (Madin-Darby canine kidney transfected with the human MDR1 gene) and investigate feasibility utilizing cell line as an vitro model study permeability biotin-conjugated prodrugs anti-HIV protease inhibitors. Mechanism [3H]biotin uptake transport was delineated. Transepithelial prodrug, i.e., biotin-saquinavir, also studied. Reverse transcription polymerase chain reaction...
Purpose: The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number diseases, but it not investigated ophthalmic diseases. Here, we evaluated the functional interleukin-1β (IL-1β), IL-6, IL-17A, and tumor necrosis factor (TNF) induction ocular inflammation.Materials Methods: We delivered adeno-associated virus (AAV) vectors expressing IL-1β, or TNF intravitreally naïve C57/BL6 mice compared contrasted inflammatory effects eye 5 weeks after AAV-mediated gene...
The highly specific S1 serine protease factor D (FD) plays a central role in the amplification of complement alternative pathway (AP) innate immune system. Genetic associations humans have implicated AP activation age-related macular degeneration (AMD), and dysfunction predisposes individuals to disorders such as paroxysmal nocturnal hemoglobinuria (PNH) atypical hemolytic uremic syndrome (aHUS). combination structure-based hit identification subsequent optimization center (S)-proline-based...
Drug delivery to the suprachoroidal space (SCS®) has become a clinical reality after 2021 FDA approval of CLS-TA, triamcinolone acetonide injectable suspension for use (XIPERE®), administered via microneedle-based device, SCS Microinjector®. Suprachoroidal (SC) facilitates targeting, compartmentalization, and durability small molecule suspensions, thereby potentially addressing some efficacy, safety, treatment burden limitations current retinal therapies. Herein, design features...
Purpose: This study evaluated ocular tolerability and transfectability of nonviral DNA nanoparticles (DNPs) after microneedle-based suprachoroidal (SC) administration, in comparison to subretinal (SR) administration. Methods: The DNPs consisted a single copy plasmid with polyubiquitin C/luciferase transcriptional cassette compacted 10 kDa PEG-substituted lysine 30-mer peptides (CK30PEG10k). New Zealand White rabbits (n = 4 per group) received unilateral SC injection (0.1 mL via microneedle...
Purpose: The overall aim of this research work was to evaluate a series dipeptide monoester prodrugs an antiviral agent, ganciclovir (GCV), for oligopeptide transporter-targeted transscleral drug delivery rabbit retina. Methods: permeability and enzymatic hydrolysis GCV were evaluated using freshly excized retinal pigment epithelium (RPE)-choroidsclera (RCS) sclera tissue preparations. Affinity transport mechanism these their translocation across RCS investigated through competitive...
Purpose: Axitinib, a tyrosine kinase inhibitor, is potent inhibitor of vascular endothelial growth factor (VEGF) receptors −1, −2 and −3. Suprachoroidal (SC) delivery axitinib, combined with pan-VEGF inhibition activity has the potential to provide additional benefits compared current standard care intravitreal anti–VEGF-A agents. This study evaluated ocular pharmacokinetics systemic disposition axitinib after SC administration in rabbits. Methods: Rabbits received as either single injection...
Purpose: The aim of this study was to determine vitreal pharmacokinetics a series dipeptide monoester ganciclovir (GCV) prodrugs and their interaction with the retinal peptide transporter. Methods: New Zealand albino male rabbits were selected as animal model. Ocular microdialysis technique employed delineate GCV, L-valine-GCV GCV (L-valine-L-valine, L-tyrosine-L-valine, L-glycine- L-valine) following intravitreal administration. Results: Val-GCV Val-Val-GCV inhibited uptake [3H]Gly-Sar by...
Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is becoming an important technology to determine the distribution of drugs and their metabolites in tissue preclinical species after dosing. Interest IMS growing ophthalmology field, but little work this point has been done investigate ocular drug transit using technology. Information on where how a distributing through eye understanding efficacy whether it reaching desired target tissue. For study, brimonidine...
Drug delivery to the retina is a challenging task owing its complex physiology and presence of blood-retinal barrier (BRB), which regulates permeation substances from blood into retina. Transporter-targeted drug has become clinically significant drug-delivery approach for enhancing bioavailability various drugs. Different nutrient transporters have been reported be expressed on Riboflavin (vitamin B2), an essential nutritional vitamin development maintenance surface structures functions...
The purpose of this study was to evaluate the implication an ex vivo model for carrier-mediated retinal drug delivery using Ussing chamber system.Dutch Belted Pigmented rabbits weighing 2-2.5 kg were used in these studies. Excised posterior segment tissues (RPE-choroid-sclera and sclera), mounted on chamber, as model. Transport studies carried out across sclera RPE-choroid-sclera (RCS) tissue preparations retina (S --> R) (R S) directions 3 hr at 37 degrees C. validated by permeability with...
Purpose. The purpose of this study was to evaluate partitioning into and transport across posterior segment tissues (sclera, retinal pigment epithelium (RPE)–choroid) AL-4940, the active metabolite angiostatic cortisene anecortave acetate (AL-3789). Methods. Transport [14C]-AL-4940 measured through RPE–choroid–sclera (RCS) sclera, excised from Dutch Belted pigmented rabbits' eyes, in directions scleral vitreal (S→V) (V→S) for 3 h at 37°C using Ussing chambers. Tissue integrity monitored by...