Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Citation - WoS: 13Citation - Scopus: 15Prevention of Cisplatin-Induced Nephrotoxicity by Kidney-Targeted siRNA Delivery(Elsevier, 2022-11) Aydin, Erkin; Cebeci, Aysun; Lekesizcan, AycaCisplatin is a potent and widely used chemotherapy agent, however, nephrotoxicity limits its use. Many patients need to pause or withdraw from chemotherapy to prevent acute kidney injury. To prevent cisplatin damage, we designed chitosan/siRNA nanoparticleswhich are nontoxic and are readily taken up by HEK293 cells. The nanoparticles contained siRNA against cationic membrane transport (OCT1&2) and apoptosis related proteins (p53, PKC8, and gamma GT). In mice treated with cisplatin, serum creatinine levels increased from 15 to 88 mg/dL and blood urea nitrogen levels increased from 0.25 to 1.7 mg/dL, however, siRNA nanoparticles significantly limited these levels to 30 mg/dL and 0.55 mg/dL, respectively. Western and IHC analyses showed lower p53, PKC8, and gamma GT expressions in siRNA treated mice. Histomorphological evaluation revealed high-level protection of kidney proximal tubules from cisplatin damage. Protein expressions and extent of kidney protection were directly correlated with number of siRNA applications. Our results suggest that this novel approach for kidney -targeted delivery of select siRNAs may represent a promising therapy for preventing cisplatin-induced nephro-toxicity. Furthermore, this or other similarly sized nanocarriers could potentially be utilized to passively target kidneys for diagnostic, protective, or treatment purposes.Article Citation - Scopus: 15Development of a Nanoparticle-Embedded Chitosan Sponge for Topical and Local Administration of Chemotherapeutic Agents(American Society of Mechanical Engineers (ASME) infocentral@asme.org, 2014-11-01) Goldberg, Manijeh; Manzi, Aaron; Aydin, Erkin; Singh, Gurtej; Khoshkenar, Payam; Birdi, Amritpreet; Chen, Julie Y.; Langer, RobertThe following work describes the development of a novel noninvasive transmucosal drug delivery system, the chitosan sponge matrix (CSM). It is composed of cationic chitosan (CS) nanoparticles (NPs) that encapsulate cisplatin (CDDP) embedded within a polymeric mucoadhesive CS matrix. CSM is designed to swell up when exposed to moisture, facilitating release of the NPs via diffusion across the matrix. CSM is intended to be administered topically and locally to mucosal tissues, with its initial indication being oral cancer (OC). Currently, intravenous (IV) administered CDDP is the gold standard chemotherapeutic agent used in the treatment of OC. However, its clinical use has been limited by its renal and hemotoxicity profile. We aim to locally administer CDDP via encapsulation in CS NPs and deliver them directly to the oral cavity with CSM. It is hypothesized that such a delivery device will greatly reduce any systemic toxicity and increase antitumor efficacy. This paper describes the methods for developing CSM and maintaining the integrity of CDDP NPs embedded in the CSM. © 2016 Elsevier B.V., All rights reserved.