Browsing by Author "Acharya, Ghanashyam"

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    Combination Nanomedicine Strategy for Preventing High-Risk Corneal Transplantation Rejection
    (American Chemical Society, 2024) Meng, Tuo; Zheng, Jinhua; Shin, Crystal S.; Gao, Nan; Bande, Divya; Sudarjat, Hadi; Chow, Woon; Halquist, Matthew Sean; Yu, Fu-Shin; Acharya, Ghanashyam; Xu, Qingguo
    High-risk (HR) corneal transplantation presents a formidable challenge, with over 50% of grafts experiencing rejection despite intensive postoperative care involving frequent topical eyedrop administration up to every 2 h, gradually tapering over 6–12 months, and ongoing maintenance dosing. While clinical evidence underscores the potential benefits of inhibiting postoperative angiogenesis, effective antiangiogenesis therapy remains elusive in this context. Here, we engineered controlled-release nanomedicine formulations comprising immunosuppressants (nanoparticles) and antiangiogenesis drugs (nanowafer) and demonstrated that these formulations can prevent HR corneal transplantation rejection for at least 6 months in a clinically relevant rat model. Unlike untreated corneal grafts, which universally faced rejection within 2 weeks postsurgery, a single subconjunctival injection of the long-acting immunosuppressant nanoparticle alone effectively averted graft rejection for 6 months, achieving a graft survival rate of ∼70%. Notably, the combination of an immunosuppressant nanoparticle and an anti-VEGF nanowafer yielded significantly better efficacy with a graft survival rate of >85%. The significantly enhanced efficacy demonstrated that a combination nanomedicine strategy incorporating immunosuppressants and antiangiogenesis drugs can greatly enhance the ocular drug delivery and benefit the outcome of HR corneal transplantation with increased survival rate, ensuring patient compliance and mitigating dosing frequency and toxicity concerns.
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    Design and Fabrication of Functional Materials in Biomedical Application
    (2023-04-20) Adumbumkulath, Aparna; Pulickel, Ajayan M; Acharya, Ghanashyam
    Advances in materials engineering have led to the development of several biomaterials for surgical implants, catheters, sutures, grafts, and drug delivery systems. However, most of the currently available biomaterials are immunogenic and fibrogenic with compliance mismatch with the host tissue and often produce toxic byproducts at the implant site. Therefore, there is an unmet need for the development of novel functional biomaterials with anti-inflammatory, anti-thrombogenic, and pro-regenerative properties, along with the ability to improve the drug efficiency by increasing the drug residence time when needed. We developed a new class of functional biopolymers incorporated with inflammation modulatory and pro-regenerative attributes and demonstrated their utility in biomedical and drug delivery applications. By programming the zeta potential, surface pH, and mechanical properties of our functional biopolymers we fabricated bioscaffolds and demonstrated their immunomodulatory properties in rat ventral hernia repair model. This study demonstrated the bioscaffold ability to modulate inflammation and fibrosis and promote regenerative healing rather than healing through tissue scarring. We developed a thromboresistant vascular graft with tunable physicochemical and mechanical properties that can mimic the surface of the host vessel and maintain long-term patency. The thromboresistance of the graft was tested in vivo in a rat aorta. The second part of this thesis focuses on the non-invasive ocular drug delivery system. Current standard of care, eyedrop treatment for eye injuries and diseases are ineffective because of the ocular surface barriers that prevent drug diffusion into the eye. In this context, we developed non-invasive drug delivery systems that can surmount the ocular barriers for the delivery of drugs for an extended period to improve the drug efficiency and patient compliance.
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    Metal-Free Dual Modal Contrast Agents Based on Fluorographene Quantum Dots
    (Wiley, 2016) Radhakrishnan, Sruthi; Samanta, Atanu; Sudeep, Parambath M.; Maldonado, Kiersten L.; Mani, Sendurai A.; Acharya, Ghanashyam; Tiwary, Chandra Sekhar; Singh, Abhishek K.; Ajayan, Pulickel M.
    Fluorographene quantum dots prepared from fluorinated graphene oxide (FGO) show a linear dependence of the magnetization on the applied field. This is further supported by DFT calculations taking into account a few possible systems of functionalized graphene quantum dots. The inherent magnetism, high concentration of fluorine and cyto-compatibility of these quantum dots promise potential application as a dual modal agent for proton and 19F based Magnetic Resonance Imaging which is investigated here. A metal free dual modal contrast agent would bring about a great change in the efficiency and resolution of this widely used imaging tool.