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Plga immunosuppressant

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...
June 2, 2016: 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
Min Beom Heo, Mi Young Cho, Yong Taik Lim
In this study, we report on polymer nanoparticles (NPs) that can induce an enhanced immune response in dendritic cell (DC)-based cancer immunotherapy by the combined delivery of tumor antigen and small interference RNA (siRNA) for the immunosuppressive gene to DCs. DCs are specialized antigen-presenting cells (APCs) that capture, process and present antigens and induce an antigen-specific cytotoxic T lymphocyte response. Because the suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of the APC-based immune response, the inhibition of SOCS1 gene expression is essential for DCs to enhance antigen-specific anti-tumor immunity...
May 2014: Acta Biomaterialia
Marcela C M Souza, Sílvia L Fialho, Pedro A F Souza, Gustavo O Fulgêncio, Gisele R Da Silva, Armando Silva-Cunha
PURPOSE: To evaluate the in vivo release and ocular toxicity of a tacrolimus-loaded PLGA intravitreal implant. METHODS: Tacrolimus-loaded PLGA implants were inserted into the vitreous cavity of rabbits' eye. At different time points, the vitreous was retrieved and the concentration of tacrolimus released from the implants was determined. Clinical examination was performed to evaluate the implant tolerance. RESULTS: PLGA implants provided controlled and prolonged release of tacrolimus...
January 2014: Current Eye Research
Michael Look, W Mark Saltzman, Joe Craft, Tarek M Fahmy
Targeting dendritic cells with nanoparticles is an attractive modality for instigating immunity or inducing immunosuppression. An important aspect of successful delivery of antigen and immune modulators to these cells is the efficacy of nanoparticle internalization, which can dictate the strength and robustness of immune responses; optimizing particulate uptake is thus key. We compared the internalization of two nanoparticulate platforms: a vesicular "nanogel" platform with a lipid exterior, and the widely-used solid biodegradable poly(lactic-co-glycolic acid) (PLGA) system...
January 2014: Biomaterials
Christian Lautenschläger, Carsten Schmidt, Claus-Michael Lehr, Dagmar Fischer, Andreas Stallmach
INTRODUCTION: The systemic therapy of inflammatory bowel diseases (IBD) by oral administration of anti-inflammatory and immunosuppressive agents is characterized by an increased probability of adverse drug reactions. A successful treatment with a simultaneous reduction in adverse events may be achieved by the administration of micro- and nanosized targeted drug delivery systems, which accumulate selectively in inflamed mucosal areas without systemic absorption. We described in a first in vivo study in IBD patients a significantly enhanced, but minor accumulation of non-functionalized poly(lactic-co-glycolic acid) (PLGA) microparticles in ulcerous lesions very recently...
November 2013: European Journal of Pharmaceutics and Biopharmaceutics
Tamiru Negash, Martin Liman, Silke Rautenschlein
Infectious bursal disease virus (IBDV) is an immunosuppressive virus of chickens. The virus protein (VP) 2 induces neutralizing antibodies, which protect chickens against the disease. The aim of this study was to develop a cationic poly(d,l-lactide-co-glycolide) (PLGA) microparticle (MP) based IBDV-VP2 DNA vaccine (MP-IBDV-DNA) for chickens to be delivered orally and by eye drop route. The tested IBDV-VP2 DNA vaccines were immunogenic for specific-pathogen-free chickens and induced an antibody response after intramuscular application...
August 12, 2013: Vaccine
Lalit Kumar, Shivani Verma, Sumit Jamwal, Shubha Vaidya, Bhuvaneshwar Vaidya
Cutaneous candidiasis is a common topical fungal infection which may be more prominent in patients associated with AIDS. It is usually treated by conventional formulations such as cream, gel, which show various adverse effects on skin along with systemic absorption. To overcome these drawbacks, various novel drug delivery systems have been explored. Poly(lactic-co-glycolic acid) (PLGA)-based microparticulate systems have shown good dermal penetration after topical application. Therefore, in the present study clotrimazole-loaded PLGA microspheres were prepared for targeted dermal delivery...
May 2014: Pharmaceutical Development and Technology
Varun Dwivedi, Cordelia Manickam, Basavaraj Binjawadagi, Dechamma Joyappa, Gourapura J Renukaradhya
Biodegradable nanoparticle-based vaccine development research is unexplored in large animals and humans. In this study, we illustrated the efficacy of nanoparticle-entrapped UV-killed virus vaccine against an economically important respiratory viral disease of pigs called porcine reproductive and respiratory syndrome virus (PRRSV). We entrapped PLGA [poly (lactide-co-glycolides)] nanoparticles with killed PRRSV antigens (Nano-KAg) and detected its phagocytosis by pig alveolar macrophages. Single doses of Nano-KAg vaccine administered intranasally to pigs upregulated innate and PRRSV specific adaptive responses...
2012: PloS One
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