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Plga immunosuppressant

Muhammad Naeem, Junhwan Bae, Murtada A Oshi, Min-Soo Kim, Hyung Ryong Moon, Bok Luel Lee, Eunok Im, Yunjin Jung, Jin-Wook Yoo
Background: Colon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer...
2018: International Journal of Nanomedicine
Michelle L Ratay, Stephen C Balmert, Ethan J Bassin, Steven R Little
Dry eye disease (DED), also known as keratoconjunctivitis sicca, is an ocular surface disease characterized by T-cell-mediated inflammation. Current therapeutics, such as immunosuppressive agents, act to suppress the clinical signs and inflammation. However, long-term usage of these treatments can cause severe side effects. In this study, we present an alternative therapeutic approach that utilizes a histone deacetylase inhibitor (HDACi) to regulate transcription of a variety of immunomodulatory genes. Specifically, HDACi have emerged as a potential anti-inflammatory agent, which can modulate the functions of a subset of suppressive T lymphocytes known as regulatory T cells (Tregs), enhancing FoxP3 acetylation and subsequently guarding the transcription factor from proteasomal degradation...
April 15, 2018: Acta Biomaterialia
Ruixiang Li, Jianming Liang, Yuwei He, Jing Qin, Huining He, Seungjin Lee, Zhiqing Pang, Jianxin Wang
The outcome of scaffold-based stem cell transplantation remains unsatisfied due to the poor survival of transplanted cells. One of the major hurdles associated with the stem cell survival is the immune rejection, which can be effectively reduced by the use of immunosuppressant. However, ideal localized and sustained release of immunosuppressant is difficult to be realized, because it is arduous to hold the drug delivery system within scaffold for a long period of time. In the present study, the sustained release of immunosuppressant for the purpose of improving the survival of stem cells was successfully realized by a nanoparticle-anchoring hydrogel scaffold we developed...
2018: Theranostics
Tung Thanh Pham, Tiep Tien Nguyen, Shiva Pathak, Shobha Regmi, Hanh Thuy Nguyen, Tuan Hiep Tran, Chul Soon Yong, Jong Oh Kim, Pil-Hoon Park, Min Hui Park, Young Kyung Bae, Jeong Uk Choi, Youngro Byun, Cheol-Hee Ahn, Simmyung Yook, Jee-Heon Jeong
This study aims to develop a novel surface modification technology to prolong the survival time of pancreatic islets in a xenogenic transplantation model, using 3,4-dihydroxyphenethylamine (DOPA) conjugated poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (DOPA-NPs) carrying immunosuppressant FK506 (FK506/DOPA-NPs). The functionalized DOPA-NPs formed a versatile coating layer for antigen camouflage without interfering the viability and functionality of islets. The coating layer effectively preserved the morphology and viability of islets in a co-culture condition with xenogenic lymphocytes for 7 days...
February 2018: Biomaterials
Annette Sommershof, Lisa Scheuermann, Julia Koerner, Marcus Groettrup
Animal tumor models and human cancer studies have provided convergent evidence that chronic psychological stress plays a decisive role in modulating anti-tumor T cell immunity. However, whether chronic stress also affects anti-cancer vaccine strategies that rely on the induction of functional tumor-specific TCD8+ cells has not been investigated yet. In this study we provide direct evidence that chronic stress suppresses the therapeutic efficacy of a biodegradable poly(d,l-lactide-co-glycolide) microsphere (PLGA-MS) based cancer vaccine in a murine melanoma model...
October 2017: Brain, Behavior, and Immunity
Yan Liang Fan, Han Wei Hou, Hui Min Tay, Wei Mei Guo, Per-Olof Berggren, Say Chye Joachim Loo
Rapamycin is commonly used in chemotherapy and posttransplantation rejection suppression, where sustained release is preferred. Conventionally, rapamycin has to be administered in excess due to its poor solubility, and this often leads to cytotoxicity and undesirable side effects. In addition, rapamycin has been shown to be hydrolytically unstable, losing its bioactivity within a few hours. The use of drug delivery systems is hypothesized to preserve the bioactivity of rapamycin, while providing controlled release of this otherwise potent drug...
October 2017: AAPS PharmSciTech
S Kuchler-Bopp, A Larrea, L Petry, Y Idoux-Gillet, V Sebastian, A Ferrandon, P Schwinté, M Arruebo, N Benkirane-Jessel
The innervation of teeth mediated by axons originating from the trigeminal ganglia is essential for their function and protection. Immunosuppressive therapy using Cyclosporine A (CsA) was found to accelerate the innervation of transplanted tissues and particularly that of bioengineered teeth. To avoid the CsA side effects, we report in this study the preparation of CsA loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles, their embedding on polycaprolactone (PCL)-based scaffolds and their possible use as templates for the innervation of bioengineered teeth...
March 1, 2017: Acta Biomaterialia
Shi-Jie Gao, Yang Liu, Han-Jie Wang, De-Xiang Ban, Shi-Zhao Cheng, Guang-Zhi Ning, Liang-Liang Wang, Jin Chang, Shi-Qing Feng
Cyclosporine-A (CsA) is an immunosuppressant agent that has shown effectiveness as a neuroprotective drug; however, it does not readily cross the blood-spinal cord barrier (BSCB), which constrains the clinical applications of CsA for the treatment of spinal cord injury (SCI). Our group recently tested the ability of novel polyethylene glycol (PEG)-transactivating-transduction protein (TAT)-modified CsA-loaded cationic multifunctional polymeric liposome-poly(lactic-co-glycolic acid) (PLGA) core/shell nanoparticles (PLGA/CsA NPs) to transport and deliver CsA across the BSCB to treat SCI...
January 2017: Journal of Drug Targeting
Koshiro Sonomoto, Kunihiro Yamaoka, Hiroaki Kaneko, Kaoru Yamagata, Kei Sakata, Xiangmei Zhang, Masahiro Kondo, Yukichi Zenke, Ken Sabanai, Shingo Nakayamada, Akinori Sakai, Yoshiya Tanaka
INTRODUCTION: Mesenchymal stem cells (MSCs) have immunosuppressive activity and can differentiate into bone and cartilage; and thus seem ideal for treatment of rheumatoid arthritis (RA). Here, we investigated the osteogenesis and chondrogenesis potentials of MSCs seeded onto nano-fiber scaffolds (NFs) in vitro and possible use for the repair of RA-affected joints. METHODS: MSCs derived from healthy donors and patients with RA or osteoarthritis (OA) were seeded on poly-lactic-glycolic acid (PLGA) electrospun NFs and cultured in vitro...
2016: PloS One
Shiva Pathak, Biki Gupta, Bijay Kumar Poudel, Tuan Hiep Tran, Shobha Regmi, Tung Thanh Pham, Raj Kumar Thapa, Min-Soo Kim, Chul Soon Yong, Jong Oh Kim, Jee-Heon Jeong
Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres (TAC-PLGA-M) can be administered for the long-term survival of transplanted organs due to their immunosuppressive activity. The purpose of our study was to optimize the parameters of the electrospray method, and to prepare TAC-PLGA-M with a high payload and desirable release properties. TAC-PLGA-M were prepared using the electrospray method. In vitro characterization and evaluation were performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy...
2016: Chemical & Pharmaceutical Bulletin
Sima Rahimian, Marieke F Fransen, Jan Willem Kleinovink, Maryam Amidi, Ferry Ossendorp, Wim E Hennink
Immunotherapy of cancer is a promising therapeutic approach which aims to eliminate malignancies by inducing or enhancing an immune response against the tumor. Immunotherapy, however, faces several challenges such as local immunosuppression in the tumor area leading to immunological tolerance. To overcome these challenges, particulate formulations such as nano- and microparticles containing immunotherapeutics have been developed to increase therapeutic efficacy and reduce toxicity of immunotherapy. Particulate formulations based on biodegradable aliphatic polyesters such as poly(lactic-co-glycolic acid) (pLGA) have been extensively used with promising results...
2015: Current Pharmaceutical Design
Ryo Kojima, Takatsune Yoshida, Hiroaki Tasaki, Hiroyuki Umejima, Masashi Maeda, Yasuyuki Higashi, Shunsuke Watanabe, Naoto Oku
The objective of this study was to elucidate the release and absorption mechanisms of tacrolimus loaded into microspheres composed of poly(lactic-co-glycolic acid) (PLGA) and/or polylactic acid (PLA). Tacrolimus-loaded microspheres were prepared by the o/w emulsion solvent evaporation method. The entrapment efficiency correlated with the molecular weight of PLGA, and the glass transition temperature of PLGA microspheres was not decreased by the addition of tacrolimus. These results indicate that intermolecular interaction between tacrolimus and the polymer would affect the entrapment of tacrolimus in the microspheres...
August 15, 2015: International Journal of Pharmaceutics
Kasra Tajdaran, Molly S Shoichet, Tessa Gordon, Gregory H Borschel
Despite substantial improvement in microsurgical techniques for nerve repair, recovery after peripheral nerve injury is usually incomplete. FK506, an FDA approved immunosuppressant, improves functional recovery and reinnervation following peripheral nerve injury in animal models. However, systemically delivered FK506 causes undesirable global immunosuppression. We have, therefore, engineered a biodegradable local delivery system for FK506 using fibrin gel as a drug reservoir that could be placed at a site of nerve injury...
September 2015: Biotechnology and Bioengineering
K R Jyothi, Jagadish Beloor, Ara Jo, Minh Nam Nguyen, Tae Gyu Choi, Jin-Hwan Kim, Salima Akter, Sang-Kyung Lee, Chi Hoon Maeng, Hyung Hwan Baik, Insug Kang, Joohun Ha, Sung Soo Kim
Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles...
2015: International Journal of Nanomedicine
Tae-Ha Song, Jinah Jang, Yeong-Jin Choi, Jin-Hyung Shim, Dong-Woo Cho
Systemic administration of the immunosuppressive drug cyclosporin A (CsA) is frequently associated with a number of side effects; therefore, sometimes it cannot be applied in sufficient dosage after allogeneic or xenogeneic cell transplantation. Local delivery is a possible solution to this problem. We used 3D printing to develop a CsA-loaded 3D drug carrier for the purpose of local and sustained delivery of CsA. The carrier is a hybrid of CsA-poly(lactic-co-glycolic acid) (PLGA) microsphere-loaded hydrogel and a polymeric framework so that external force can be endured under physiological conditions...
2015: Cell Transplantation
Qing Pan, Qingguo Xu, Nicholas J Boylan, Nicholas W Lamb, David G Emmert, Jeh-Chang Yang, Li Tang, Tom Heflin, Saeed Alwadani, Charles G Eberhart, Walter J Stark, Justin Hanes
Immunologic graft rejection is one of the main causes of short and long-term graft failure in corneal transplantation. Steroids are the most commonly used immunosuppressive agents for postoperative management and prevention of corneal graft rejection. However, steroids delivered in eye drops are rapidly cleared from the surface of the eye, so the required frequency of dosing for corneal graft rejection management can be as high as once every 2h. Additionally, these eye drops are often prescribed for daily use for 1 year or longer, which can result in poor patient compliance and steroid-related side effects...
March 10, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Tan Ding, Chao Zhu, Zhen-Zhen Kou, Jun-Bin Yin, Ting Zhang, Ya-Cheng Lu, Li-Ying Wang, Zhuo-Jing Luo, Yun-Qing Li
AIMS: To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. MAIN METHODS: We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1...
September 1, 2014: Life Sciences
Hongling Liu, Yanyan Zhang, Haiyan Ma, Chunmei Zhang, Shaoying Fu
BACKGROUND: Posterior capsule opacification (PCO) is a common complication after cataract surgery. The purpose of this study was to determine the effects of three administering ways of rapamycin (RAPA) on the formation of PCO in rabbit eyes for 12 weeks. METHODS: Eighty rabbits were divided into four groups, according to the different administrations of RAPA which they received. These were: (1) the control group, (2) the irrigation-treated group - 5 ng/ml intraoperative RAPA irrigation solution, (3) the eye-drop-treated group - 2 mg/ml RAPA eye drops, and (4) the IOL-treated group - RAPA-poly(lactic-co-glycolic) acid (PLGA) loaded on the surface of intraocular lens (IOLs) (RAPA-PLGA-IOLs)...
July 2014: Graefe's Archive for Clinical and Experimental Ophthalmology
Jamal S Lewis, Chris Roche, Ying Zhang, Todd M Brusko, Clive H Wasserfall, Mark Atkinson, Michael J Clare-Salzler, Benjamin G Keselowsky
Microparticulate systems are beginning to show promise for delivery of modulatory agents for immunotherapeutic applications which modulate dendritic cell (DC) functions. Co-administration of multiple factors is an emerging theme in immune modulation which may prove beneficial in this setting. Herein, we demonstrate that localized, controlled delivery of multiple factors can be accomplished through poly (lactic-co-glycolic acid) (PLGA) microparticle systems fabricated in two size classes of phagocytosable and unphagocytosable microparticles (MPs)...
May 7, 2014: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Basavaraj Binjawadagi, Varun Dwivedi, Cordelia Manickam, Kang Ouyang, Yun Wu, Ly James Lee, Jordi B Torrelles, Gourapura J Renukaradhya
Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRRS outbreaks. Recently, we have shown that poly(lactic-co-glycolic) acid (PLGA) nanoparticle-entrapped inactivated PRRSV vaccine (NP-KAg) induces a cross-protective immune response in pigs. To further improve its cross-protective efficacy, the NP-KAg vaccine formulation was slightly modified, and pigs were coadministered the vaccine twice intranasally with a potent adjuvant: Mycobacterium tuberculosis whole-cell lysate...
2014: International Journal of Nanomedicine
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