Synthesis and Physicochemical Characterization of Biodegradable PLGA-based Magnetic Nanoparticles Containing Amoxicilin

Somayeh Alimohammadi,Roya Salehi, Niloofar Amini,Soodabeh Davaran,Niloofar Amini 대한화학회 2012 Bulletin of the Korean Chemical Society Vol.33 No.10

The purposes of this research were to synthesize amoxicillin-carrying magnetic nanoparticles. Magnetic nanoparticles were prepared by a chemical precipitation of ferric and ferrous chloride salts in the presence of a strong basic solution. PLGA and PLGA-PEG copolymers were prepared by ring opening polymerization of lactide (LA) and glycolide (GA) (mole ratio of LA: GA 3:1) with or without polyethylene glycol (PEG). Amoxicillin loaded magnetic PLGA and PLGA-PEG nanoparticles were prepared by an emulsion-evaporation process (o/w). Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) photomicrographs showed that the magnetic nanoparticles have the mean diameter within the range of 65-260 nm also they were almost spherical in shape. Magnetic nanoparticles prepared with PLGA showed more efficient entrapment (90%) as compared with PLGA-PEG (48-52%) nanoparticles. In-vitro release of amoxicillin from magnetic PLGA nanoparticles showed that 78% of drug was released over 24 hours. The amount of amoxicillin released from PLGA-PEG s was higher than PLGA.

Synthesis and Physicochemical Characterization of Biodegradable PLGA-based Magnetic Nanoparticles Containing Amoxicilin

Alimohammadi, Somayeh,Salehi, Roya,Amini, Niloofar,Davaran, Soodabeh Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.10

The purposes of this research were to synthesize amoxicillin-carrying magnetic nanoparticles. Magnetic nanoparticles were prepared by a chemical precipitation of ferric and ferrous chloride salts in the presence of a strong basic solution. PLGA and PLGA-PEG copolymers were prepared by ring opening polymerization of lactide (LA) and glycolide (GA) (mole ratio of LA: GA 3:1) with or without polyethylene glycol (PEG). Amoxicillin loaded magnetic PLGA and PLGA-PEG nanoparticles were prepared by an emulsion-evaporation process (o/w). Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) photomicrographs showed that the magnetic nanoparticles have the mean diameter within the range of 65-260 nm also they were almost spherical in shape. Magnetic nanoparticles prepared with PLGA showed more efficient entrapment (90%) as compared with PLGA-PEG (48-52%) nanoparticles. In-vitro release of amoxicillin from magnetic PLGA nanoparticles showed that 78% of drug was released over 24 hours. The amount of amoxicillin released from PLGA-PEG s was higher than PLGA.

Blood-Compatible and Biodegradable Polymer-Coated Drug-Eluting Stent

박준규,나재운,김동곤,배인호,임경섭,정명호,최창용,최수경,김상채 한국고분자학회 2015 Macromolecular Research Vol.23 No.3

A drug-eluting stent (DES) is a metal stent that has been coated with a drug known to suppress restenosis. To prepare a novel DES, a bare metal stent (BMS) was coated with sirolimus (SRL) in a blood-compatible, biodegradablepolymer, poly lactic-glycolic acid, grafted with poly ethylene glycol (PLGA-PEG), by an ultrasonic spraymethod. The PLGA-PEG-coated DES was designed to control the drug release-rate by varying the PEG content inthe polymer. The release behavior of SRL from the DES showed a burst-release pattern in 7 days and then sustainedreleaseover 21 days. The amount of SRL released increased with increasing PEG content in the polymer up to 15%. The PLGA-PEG copolymer coated on the stent showed the potential to act as a bio-degradable drug reservoir. In anin vitro platelet adhesion test, the PLGA-PEG15-coated DES showed significantly reduced platelet deposition versusthe BMS. The DES revealed anti-thrombotic activity and blood-compatibility presumably due to the increasedhydrophilicity of the surface of the stent and the amount of SRL loading corresponding to the high PEG content in thepolymer. In an animal study, the restenosis rate was reduced in the PLGA-PEG15-coated DES group (20.2±11.02%)versus the BMS group (44.2±12.11%). The PLGA-PEG15-coated DES inhibited smooth muscle cell (SMC) proliferationand prevented in-stent restenosis (ISR) in in vivo test. We successfully obtained the PLGA-PEG15-coatedDES with smooth surface and sustained drug-release properties.

골조직 재생을 위한 자유형상제작 기반 BMP-2 서방출형 HA-PLGA 인공지지체 개발

심진형(Jin-Hyung Shim),박정규(Jung Kyu Park),김종영(Jong Young Kim),강경신(Kyung Shin Kang),한세광(Sei Kwang Hahn),조동우(Dong-Woo Cho) 대한기계학회 2010 대한기계학회 춘추학술대회 Vol.2010 No.11

Solid freeform fabrication (SFF) based three dimensional scaffolds for bone regeneration were successfully fabricated with blend of poly(lactic-co-glycolic acid) grafted hyaluronic acid (HA-PLGA) and polyethyleneglycol (PEG) encapsulating intact BMP-2. HA-PLGA was synthesized by the conjugation between adipic acid modified HA (HA-ADH) and PLGA. PEG was blended with HA-PLGA to encapsulate BMP-2 in chloroform without denaturation, which were exploited to fabricate tissue engineered scaffolds. Multi-head deposition system, a SFF technology, was used to fabricate 3D scaffolds. In-vitro release tests confirmed the sustained release of intact BMP-2 from the scaffolds up to a month. After the in-vitro assessments of proliferation and differentiation, the blended HA-PLGA/PEG/BMP-2 scaffolds were implanted into the calvarial bone defects in SD rats. Micro-CT and histological analyses revealed effects of HA-PLGA/PEG/BMP-2 scaffolds on bone regeneration.

Preparation and characterization of biodegradable nanoparticles entrapping immunodominant peptide conjugated with PEG for oral tolerance induction

Lee, Woo-kyoung,Park, Jong-yeun,Jung, Sangho,Yang, Chul Woo,Kim, Wan-Uk,Kim, Ho-Youn,Park, Jae-Hun,Park, Jong-sang Elsevier 2005 Journal of controlled release Vol.105 No.1

<P><B>Abstract</B></P><P>PEG-conjugated immunodominant peptides for collagen-induced arthritis (CIA) were prepared for oral tolerance induction instead of whole Type II collagen (CII), because a small peptide can be converted to a macromolecule soluble in methylene chloride by the coupling of poly-ethylene glycol (PEG). PEG-pep1 was synthesized from a peptide and mPEG-NH<SUB>2</SUB> (Mw ∼5000) using SPDP as a linker, whereas PEG-pep2 was prepared by the direct disulfide coupling between PEG-OD (Mw ∼10,000) and the peptide. PEG-pep1 and PEG-pep2 were purified by gel permeation chromatography (GPC), and the peak fractions of GPC were identified by GPC and MALDI-TOF mass spectroscopy. The peptide coupling gave much earlier retention times for PEG-pep1 (11.26 min) and PEG-pep2 (10.61 min) than for mPEG-SPDP (15.63 min) and mPEG-OD (14.58 min). The Mw's of mPEG-NH<SUB>2</SUB>, mPEG-SPDP, PEG-pep1, mPEG-OD and PEG-pep2 were 5451, 5588, 7035, 10,360 and 11,826, respectively, suggesting that PEG-pep1 and PEG-pep2 of high purity could be obtained. The nanoparticles entrapping PEG-pep1 and PEG-pep2 (NP/PEG-pep1 and NP/PEG-pep2) were prepared by the o/w solvent evaporation method, whereas the peptide-loaded nanoparticles (NP/pep) were prepared by the w/o/w double emulsion method. Although all the nanoparticles had a similar spherical morphology under scanning electron microscopy, NP/pep showed up as having a larger mean size than the others, which was confirmed by dynamic light scattering analysis (NP/pep, 499.7±27.2 nm; NP/PEG-pep1, 333.0±16.8 nm; NP/PEG-pep2, 342.4±15.1 nm). The lower encapsulation efficiency of NP/pep (21.0±1.6%) than NP/PEG-pep1 (66.5±5.0%) and NP/PEG-pep2 (73.8±5.5%) can also be attributed to the preparation method. In in vitro release studies, NP/PEG-pep1 and NP/PEG-pep2 displayed a similar release profile, close to a linear release pattern, whereas NP/pep displayed a tri-phasic release profile. From these results, it was demonstrated that nanoparticles entrapping a PEG-conjugated peptide could be an alternative delivery method for the induction of oral tolerance rather than CII and peptide.</P>

Upregulation of Mir-34a in AGS Gastric Cancer Cells by a PLGA-PEG-PLGA Chrysin Nano Formulation

Mohammadian, Farideh,Abhari, Alireza,Dariushnejad, Hassan,Zarghami, Faraz,Nikanfar, Alireza,Pilehvar-Soltanahmadi, Yones,Zarghami, Nosratollah Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18

Background: Nano-therapy has the potential to revolutionize cancer therapy. Chrysin, a natural flavonoid, was recently recognized as having important biological roles in chemical defenses and nitrogen fixation, with anti-inflammatory and anti-oxidant effects but the poor water solubility of flavonoids limitstheir bioavailability and biomedical applications. Objective: Chrysin loaded PLGA-PEG-PLGA was assessed for improvement of solubility, drug tolerance and adverse effects and accumulation in a gastric cancer cell line (AGS). Materials and Methods: Chrysin loaded PLGA-PEG copolymers were prepared using the double emulsion method (W/O/W). The morphology and size distributions of the prepared PLGA-PEG nanospheres were investigated by 1H NMR, FT-IR and SEM. The in vitro cytotoxicity of pure and nano-chrysin was tested by MTT assay and miR-34a was measured by real-time PCR. Results: 1H NMR, FT-IR and SEM confirmed the PLGA-PEG structure and chrysin loaded on nanoparticles. The MTT results for different concentrations of chrysin at different times for the treatment of AGS cell line showed IC50 values of 68.2, 56.2 and $42.3{\mu}M$ and 58.2, 44.2, $36.8{\mu}M$ after 24, 48, and 72 hours of treatment, respectively for chrysin itslef and chrysin-loaded nanoparticles. The results of real time PCR showed that expression of miR-34a was upregulated to a greater extent via nano chrysin rather than free chrysin. Conclusions: Our study demonstrates chrysin loaded PLGA-PEG promises a natural and efficient system for anticancer drug delivery to fight gastric cancer.

MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head

Zhang Ying,Li Chuan,Wei Qiushi,Yuan Qiang,He Wei,Zhang Ning,Dong Yiping,Jing Zhenhao,Zhang Leilei,Wang Haibin,Cao Xiangyang 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.1

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH. BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

Poly(ethylene glycol)-poly(lactic-co-glycolic acid) core-shell microspheres with enhanced controllability of drug encapsulation and release rate.

Cha, Chaenyung,Jeong, Jae Hyun,Kong, Hyunjoon VSP 2015 Journal of Biomaterials Science. Polymer Edition Vol.26 No.13

<P>Poly(lactic-co-glycolic acid) (PLGA) microspheres have been widely used as drug carriers for minimally invasive, local, and sustained drug delivery. However, their use is often plagued by limited controllability of encapsulation efficiency, initial burst, and release rate of drug molecules, which cause unsatisfactory outcomes and several side effects including inflammation. This study presents a new strategy of tuning the encapsulation efficiency and the release rate of protein drugs from a PLGA microsphere by filling the hollow core of the microsphere with poly(ethylene glycol) (PEG) hydrogels of varying cross-linking density. The PEG gel cores were prepared by inducing in situ cross-linking reactions of PEG monoacrylate solution within the PLGA microspheres. The resulting PEG-PLGA core-shell microspheres exhibited (1) increased encapsulation efficiency, (2) decreased initial burst, and (3) a more sustained release of protein drugs, as the cross-linking density of the PEG gel core was increased. In addition, implantation of PEG-PLGA core-shell microspheres encapsulated with vascular endothelial growth factor (VEGF) onto a chicken chorioallantoic membrane resulted in a significant increase in the number of new blood vessels at an implantation site, while minimizing inflammation. Overall, this strategy of introducing PEG gel into PLGA microspheres will be highly useful in tuning release rates and ultimately in improving the therapeutic efficacy of a wide array of protein drugs.</P>

In vitro controlled release of tuberculosis drugs by amphiphilic branched copolymer nanoparticles

Mani Gajendiran,조희정,김효범,Sengottuvelan Balasubramanian 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.77 No.-

Poly(lactic-co-glycolic acid) (PLGA)-poly ethylene glycol (PEG) based amphiphilic branched copolymernanoparticles (NPs) have been developed for controlled release of tuberculosis (TB) drugs which includerifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ). The drug loading efficiency and the percentagedrug content of polymer NPs increase by increasing the amount of PEG content in polymer NPs. Thebranched PLGA-PEG based copolymer NPs exhibit initial burst release followed by sustained release ofRIF for 840 h, INH for 72 h, and PYZ for 720 h. The branched citrate-PEG-PLGA copolymer NPs can act aspotential drug carriers when compared to their linear analogues.

Comparison of Inhibitory Effect of 17-DMAG Nanoparticles and Free 17-DMAG in HSP90 Gene Expression in Lung Cancer

Mellatyar, Hassan,Akbarzadeh, Abolfazl,Rahmati, Mohammad,Ghalhar, Masoud Gandomkar,Etemadi, Ali,Nejati-Koshki, Kazem,Zarghami, Nosratallah,Barkhordari, Amin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: Up-regulation of hsp90 gene expression occurs in numerous cancers such as lung cancer. D,L-lactic-co-glycolic acid-poly ethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG may inhibit the expression. The purpose of this study was to examine whether nanocapsulating 17DMAG improves the anti cancer effect over free 17DMAG in the A549 lung cancer cell line. Materials and Methods: Cells were grown in RPMI 1640 supplemented with 10% FBS. Capsulation of 17DMAG is conducted through double emulsion, then the amount of loaded drug was calculated. Other properties of this copolymer were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity on the grown of lung cancer cell line was carried out through MTT assay. After treatment, RNA was extracted and cDNA was synthesized. In order to assess the amount of hsp90 gene expression, real-time PCR was performed. Results: In regard to the amount of the drug load, IC50 was significant decreased in nanocapsulated(NC) 17DMAG in comparison with free 17DMAG. This was confirmed through decrease of HSP90 gene expression by real-time PCR. Conclusions: The results demonstrated that PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of hsp90 expression by enhancing uptake by cells. Therefore, PLGA-PEG could be a superior carrier for this kind of hydrophobic agent.