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( Jong Min Kim ),( Tae Sung Han ),( Myoung Hwan Kim ),( Daniel S. Oh ),( Seong Soo Kang ),( Gon Hyung Kim ),( Tae Yub Kwon ),( Kyo Han Kim ),( Kyu Bok Lee ),( Jun Sik Son ),( Seok Hwa Choi ) 한국조직공학·재생의학회 2012 조직공학과 재생의학 Vol.9 No.3
The goal of this study was to develop a bioactive hydroxyapatite (HA) scaffold as a calcium phosphatebased bioceramic using drug-loaded polymeric microspheres for bone regeneration. Dexamethasone (DEX) as a model bioactive molecule and poly (lactic-co-glycolic acid) (PLGA) microspheres as a carrier were employed. Polyethyleneimine was coated on DEX-loaded PLGA microsphere surfaces, resulting in a net positively-charged surface. With such modification of the PLGA microsphere surfaces, DEX-loaded PLGA microspheres were immobilized on the negatively charged HA scaffold surfaces. The release profile of DEX over a 4-week immersion study indicated an initial burst release followed by a sustained release. In vivo evaluation of the defects filled with DEX-loaded HA scaffolds indicated that new bone formation was enhanced when compared to defects that were either unfilled or filled only with HA scaffold. This innovative platform for bioactive molecule delivery more potently induced osteogenesis in vivo, which may be exploited in implantable bone graft substitutes for stem cell therapy or improved in vivo performance.
Jun‑Pil Jee,Won Young Lee,Md. Asadujjaman 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.4
Background Long-acting injectable formulations (LAIFs) have received substantial attention recently due to their advantages over conventional formulations, including easy administration, continuous and controlled release of drug over months, and the ability to maintain drug concentrations within the therapeutic range. The constant advances in biotechnology produce complex active pharmaceuticals that might be difficult to administer by conventional means. In particular, peptides, proteins, and antibodies are hard to administer orally given their physicochemical instability in the gastrointestinal tract and short half lives in blood. Therefore, LAIFs are a good candidate delivery system for such drugs. LAIFs reduce the frequency of application and improve patient compliance. For instance, LAIF-based antipsychotics can be more effective in patients with bipolar disorder and schizoaffective disorder. Area covered This review provides an overview of the various drug delivery technologies using LAIFs. Poly (lactic-coglycolic acid) microspheres, hydrogels, organogels, and liquid crystals were chosen as representative LAIFs, and their preparation methods, advantages, limitations, challenges, and prospects are discussed. Expert opinion LAIFs are an attractive delivery system for bio-macromolecules that might participate in the new drug paradigm in the future. While each LAIF-based delivery technology has its own unique advantages, there are still some limitations that need to be overcome, and studies are being performed to understand and address these limitations.
Sellers, D.L.,Kim, T.H.,Mount, C.W.,Pun, S.H.,Horner, P.J. IPC Science and Technology Press 2014 Biomaterials Vol.35 No.31
Components of the blood have been proposed as potential therapeutic targets for improving cellular regeneration after injury and neurodegenerative disease. In this work, thrombin is shown to increase endogenous neural progenitor proliferation in the intact murine spinal cord. A local injection of heparin before a spinal cord injury reduces cell proliferation and astrogliogenesis associated with scarring. We sought to create depot-formulations of PLGA microsphere and Pluronic F-127 for sustained local delivery of two thrombin inhibitors, heparin and hirudin. Each hydrogel depot-formulation showed delayed drug release compared to microspheres or hydrogel alone. Animals with a lateral demyelination lesion showed a reduction in CD68+ macrophages when treated with hirudin-loaded PLGA/F-127 gels compared to control and heparin-treated animals. Moreover, hirudin-loaded materials showed an accelerated recovery in coordinated stepping and increased oligodendrocyte densities. Together, these data demonstrate that controlled delivery of hirudin accelerates functional recovery from a demyelination lesion in the spinal cord.
Kim Joon-Kyu,Go Eun-Jin,Ko Kyoung-Won,오현지,Han Jieun,Han Dong Keun,박우람 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.4
BACKGROUND: Poly(lactic-co-glycolic acid) (PLGA) microspheres have been actively used in various pharmaceutical formulations because they can sustain active pharmaceutical ingredient release and are easy to administer into the body using a syringe. However, the acidic byproducts produced by the decomposition of PLGA cause inflammatory reactions in surrounding tissues, limiting biocompatibility. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive because it has an acid-neutralizing effect. METHODS: To improve the encapsulation efficiency of hydrophilic MH, the MH particles were capped with hydrophobic ricinoleic acid (RA-MH). PLGA microspheres encapsulated with RA-MH particles were manufactured by the O/W method. To assess the in vitro cytotoxicity of the degradation products of PLGA, MH/PLGA, and RA-MH/PLGA microspheres, CCK-8 and Live/Dead assays were performed with NIH-3T3 cells treated with different concentrations of their degradation products. In vitro anti-inflammatory effect of RA-MH/PLGA microspheres was evaluated with quantitative measurement of pro-inflammatory cytokines. RESULTS: The synthesized RA-MH was encapsulated in PLGA microspheres and displayed more than four times higher loading content than pristine MH. The PLGA microspheres encapsulated with RA-MH had an acid-neutralizing effect better than that of the control group. In an in vitro cell experiment, the degradation products obtained from RA-MH/PLGA microspheres exhibited higher biocompatibility than the degradation products obtained from PLGA microspheres. Additionally, the RA-MH/PLGA microsphere group showed an excellent anti-inflammatory effect. CONCLUSION: Our results proved that RA-MH-encapsulated PLGA microspheres showed excellent biocompatibility with an anti-inflammatory effect. This technology can be applied to drug delivery and tissue engineering to treat various incurable diseases in the future.
( Shiva Pathak ),( Biki Gupta ),( Bijay Kumar Poudel ),( Tuan Hiep Tran ),( Shibha Regmi ),( Tung Thanh Pham ),( Raj Kumar Thapa ),( Min Soo Kim ),( Chul Soon Yong ),( Jong Oh Kim ),( Jee Heon Jeong ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Tacrolimus-loaded poly(lactic-co-glycolic acid) micro spheres (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 clcctrospray method, and to prepare T AC-PLGA-M with a high payload and desirable release properties. TAC-PLGA-M were prepared using the electrospray method. III vitro characterization and evaluation were performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Drug-loading efficiency was greater than 80% in all formulations with a maximum loading capacity of 16.81±0.37%. XRD and DSC studies suggested that the drug was incorporated in an amorphous state or was molecularly dispersed in the microspheres. The ill vitro release study showed prolonged release patterns. TAC-PLGA-M with enhanced drug loading and prolonged-release patterns were successfully prepared using the electro-spray method.
Regmi, Shobha,Cao, Jiafu,Pathak, Shiva,Gupta, Biki,Kumar Poudel, Bijay,Tung, Pham Thanh,Yook, Simmyung,Park, Jun-Beom,Yong, Chul Soon,Kim, Jong Oh,Yoo, Jin-Wook,Jeong, Jee-Heon Elsevier 2017 International journal of pharmaceutics Vol.520 No.1
<P><B>Abstract</B></P> <P>Stem cell therapy is an attractive approach to bone tissue regeneration. Nitric oxide (NO) has been reported to facilitate osteogenic differentiation of stem cells. To enhance osteogenic differentiation of gingiva-derived mesenchymal stem cells (GMSCs), we designed a method for <I>in situ</I> delivery of exogenous NO to these cells. A NO donor, polyethylenimine/NONOate, was incorporated into poly(lactic-co-glycolic acid) microspheres to deliver NO to the cells for an extended period of time under <I>in vitro</I> culture conditions. A hybrid aggregate of GMSCs and NO-releasing microspheres was prepared by the hanging drop technique. Confocal microscopy revealed homogeneous arrangement of the stem cells and microspheres in heterospheroids. Western blot analysis and live–dead imaging showed no significant change in cell viability. Importantly, the <I>in situ</I> delivery of NO within the heterospheroids enhanced osteogenic differentiation indicated by a 1.2-fold increase in alkaline phosphatase activity and an approximately 10% increase in alizarin red staining. In addition, a low dose of NO promoted proliferation of the GMSCs in this 3D system. Thus, delivery of the NO-releasing microsphers to induce differentiation of stem cells within this three dimensional system may be one of possible strategies to direct differentiation of a stem cell-based therapeutic agent toward a specific lineage.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
배윤주,조치흥,이우종,허증수,임정옥 한국조직공학과 재생의학회 2016 조직공학과 재생의학 Vol.13 No.1
Growth factors play multiple and critical roles in wound repair processes. Platelet-derived growth factor (PDGF) is a potent growth factor that is particularly important in the early inflammatory phase of wound healing. In order to extend the half-life of PDGF, polymeric encapsulation is used. In the current study, Poly (lactic-co-glycolic acid) (PLGA) microspheres containing recombinant human (rh) PDGF-BB were prepared to prolong the effectiveness of this growth factor. PLGA microspheres were optimized using a modified w/o/w-double-emulsion/solvent evaporation method by changing the processing conditions of stirring speed and emulsifier (polyvinyl alcohol) concentration. Microspheres prepared using the optimized method released rhPDGF-BB for up to three weeks. An in vitro migration assay showed a significant decrease in the wound area in cells treated with rhPDGF-BB microspheres compared to control cells. These findings demonstrate the potential of rhPDGF-BB encapsulated in microspheres to enhance wound healing.
Pathak, Shiva,Regmi, Shobha,Gupta, Biki,Poudel, Bijay K.,Pham, Tung Thanh,Kim, Jae-Ryong,Park, Pil-Hoon,Yong, Chul Soon,Kim, Jong Oh,Bae, Young Kyung,Kim, Sang Kyoon,Jeong, Jee-Heon American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.39
<P>Hypoxic or near-anoxic conditions that occur in the core of transplanted islets induce necrosis and apoptosis during the early stages after transplantation, primarily due to loss of vascularization during the isolation process. Moreover, secretion of various cytokines from pancreatic islets is detrimental to the viability of islet cells in vitro. In this study, we aimed to protect pancreatic islet cells against apoptosis by establishing a method for in situ delivery of curcumin to the pancreatic islets. Self-assembled heterospheroids composed of pancreatic islet cells and curcumin-loaded polymeric micro spheres were prepared by the three-dimensional cell culture technique. Release of curcumin in the microenvironment of pancreatic islets promoted survival of the islets. In hypoxic culture conditions, which mimic the in vivo conditions after transplantation, viability of the islets was significantly improved, as indicated by a decreased expression of pro-apoptotic protein and an increased expression of anti-apoptotic protein. Additionally, oxidative stress-induced cell death was suppressed. Thus, unlike co-transplantation of pancreatic islets and free microspheres, which provided a wide distribution of microspheres throughout the transplanted area, the heterospheroid transplantation resulted in colocalization of pancreatic islet cells and microspheres, thereby exerting beneficial effects on the cells.</P>