• Title/Summary/Keyword: drug carriers

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pH-Sensitivity Control of PEG-Poly(${\beta}$-amino ester) Block Copolymer Micelle

  • Hwang, Su-Jong;Kim, Min-Sang;Han, Jong-Kwon;Lee, Doo-Sung;Kim, Bong-Sup;Choi, Eun-Kyung;Park, Heon-Joo;Kim, Jin-Seok
    • Macromolecular Research
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    • v.15 no.5
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    • pp.437-442
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    • 2007
  • Poly(ethylene glycol) methyl ether (PEG)-poly(${\beta}$-amino ester) (PAE) block copolymers were synthesized using a Michael-type step polymerization, and the construction of pH-sensitive polymeric micelles (PM) investigated. The ${\beta}$-amino ester block of the block copolymers functioned as a pH-sensitive moiety as well as a hydrophobic block in relation to the ionization of PAE, while PEG acted as a hydrophilic block, regardless of ionization. The synthesized polymers were characterized using $^1H-NMR$, with their molecular weights measured using gel permeation chromatography. The $pK_b$ values of the pH-sensitive polymers were measured using a titration method. The pH-sensitivity and critical micelle concentration (CMC) of the block copolymers in PBS solution were estimated using fluorescence spectroscopy. The pH dependent micellization behaviors with various bisacrylate esters varied within a narrow pH range. The critical micelle concentration at pH 7.4 decreased from 0.032 to 0.004 mg/mL on increasing the number of methyl group in the bisacrylate from 4 to 10. Also, the particle size of the block copolymer micelles was determined using dynamic light scattering (DLS). The DLS results revealed the micelles had an average size below 100 nm. These pH-sensitive polymeric micelles may be good carriers for the delivery of an anticancer drug.

Clinical Application of Exosomes for COVID-19 and Diagnosis (COVID-19 치료 및 진단을 위한 Exosome의 임상적 적용)

  • June Seok HEO
    • Korean Journal of Clinical Laboratory Science
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    • v.56 no.1
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    • pp.1-9
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    • 2024
  • Exosomes are nano-sized membrane-bound extracellular vesicles containing various biological molecules, such as nucleic acids, proteins, and lipids, which can be used to modulate physiological processes. The exosomal molecules secreted by cells can be extensively used as tools for diagnosis and therapy. Exosomes carry specific molecules released by the cells they originate from, which can be transferred to surrounding cells or tissues by the exosome. For these reasons, exosomes can be exploited as biomarkers for diagnosis, carriers for drug delivery, as well as therapeutics. In stem cell technology, exosomes have been an attractive option because they can be used as safer therapeutic agents for stem cell-based cell-free therapy. Recently, studies have demonstrated the safety and efficacy of mesenchymal stem cell-derived exosomes in alleviating symptoms associated with coronavirus disease 2019 as they have anti-inflammatory and immunomodulatory potential. Performing multiple studies on exosomes would provide innovative next-generation options for clinical diagnostics and therapy. This review summarizes the use of exosomes focusing on their diverse roles. In addition, the potential of exosomes is illustrated with a focus on how exosomes can be exploited as powerful tools in the days to come.

Effect of PEG chain additive on 6,8-dichloro-2-phenylimidazo[1,2-a] pyridineacetamide (CB185) as a TSPO-binding ligand

  • Lee, Won Chang;Lee, Sang Hee;Denora, Nunzio;Laquintana, Valentino;Lee, Byung Chul;Kim, Sang Eun
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.2
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    • pp.89-100
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    • 2019
  • In our previous studies, we developed a 18F-labeled TSPO-binding ligand, named [18F]CB251, which has been proved to be a promising TSPO-binding PET radiotracer for the detection and monitoring of TSPO expression in pathological diseases. (Ki = 0.27 nM for TSPO, 1.96% ID/g of tumor uptake at 1h post-injection) Based on these results, we utilized 6,8-dichloro-2-phenylimidazo[1,2-a]pyridineacetamide analogs, CB185 (1) as a targeting moiety for the selective delivery of probes and anticancer molecules to TSPO-overexpressed tissues. In this study, we designed CB185 derivatives contains different PEG chains (n = 1, 3 and 5) and fluorescence dye (Cy5) to identify the necessary space between a TSPO-binding ligand and an anticancer agent. Three CB185 derivatives (11a-c) which contains Cy5 and PEG chain, were synthesized and the effect of PEG additive on their TSPO-binding affinities were evaluated using in vitro assays. The binding affinity for compounds 11a-c was lower than that of PK11195 (Ki = 3.2 nM), but still characterized by nanomolar binding affinity for TSPO (Ki = 46.5 nM for 11a, 51.0 nM for 11b, and 388.5 nM for 11c). These results showed that the conjugates are characterized by a moderate binding affinity toward TSPO except for compound 11c, which PEG chain consist of five PEG monomers. Our finding might add useful information to decide the appropriate PET chain length for developing new TSPO-targeting drug carriers.

Dissolution and Duodenal Permeation Characteristics of Lovastatin from Bile Salt Solid Dispersions (담즙산염과의 고체분산체로부터 로바스타틴의 용출 및 십이지장 점막 투과 특성)

  • Chun, In-Koo
    • Journal of Pharmaceutical Investigation
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    • v.39 no.2
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    • pp.97-106
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    • 2009
  • Although lovastatin (LS) is widely used in the treatment of hypercholesterolemia, its bioavailability is known to be around 5%. This study was aimed to increase the solubility and dissolution-permeation rates of LS using solid dispersions (SDs) with bile salts. The solubilities of LS in water, aqueous bile salt solutions and non-aqueous vehicles were determined, and effects of bile salts on the cellulose or duodenal permeation of LS from SDs were evaluated using a horizontal permeation system. SDs were prepared at various ratios of LS to carriers, such as sodium deoxycholate (SDC), sodium glycocholate (SGC) and/or 2-hydroxypropyl-$\beta$-cyclodextrin (HPCD). The addition of bile salts (25 mM) in water increased markedly the solubility of LS by the micellar solubilization. Some non-aqueous vehicles were effective in solubilizing LS. From differential scanning calorimetric studies, it was found that the crystallinity of LS in SDs disappeared, indicating a formation of amorphous state. The SDs showed markedly enhanced dissolution compared with those of their physical mixtures (PMs) and drug alone. In the dissolution-permeation studies using a cellulose membrane, the donor and receptor solutions were maintained as a sink condition using pH 7.0 phosphate buffer containing 0.05% sodium lauryl sulfate (SLS). The flux of LS alone was nearly same as that of LS-SDC-HPCD (1:3:6) PM. However, the flux of LS-SDC-HPCD (1:3:6) SD slightly increased compared with drug alone and PM, suggesting that entrapment of LS in micelles does not significantly hinder the permeation across cellulose membrane. In the dissolution-duodenal permeation studies using a LS-HPCD-SDC (1:3:6) SD, the addition of various bile salts in donor solutions (25 mM) enhanced the permeation of LS markedly, and the fluxes were found to be $0.69{\pm}0.41$, $0.87{\pm}0.51$, $0.84{\pm}0.46$, $0.47{\pm}0.17$ and $0.68{\pm}0.32{\mu}g/cm^2/hr$ for sodium cholate (SC), SDC, SGC, sodium taurodeoxycholate (STDC) and sodium taurocholate (STC), respectively. The stepwise increase of donor SGC concentration increased the flux dose-dependently. From the relationship of donor SGC concentration and flux, the concentration of SGC initiating the permeation across the duodenal mucosa was calculated to be 11.1 mM, which is nearly same as the critical micelle concentration (CMC, 11.6 mM) of SGC. However, with no addition of bile salts and below CMC, the permeation was very limited and irratic, indicating that LS itself is very poor permeable. Higher protions of bile salt in SD such as LS-SDC or LS-SGC (1 : 49 and 1 : 69) showed highly promoted fluxes. In conclusion, SD systems with bile salts, which may form their micelles in intestinal fluids, might be a promising means for providing enhanced dissolution and intestinal permeation of practically insoluble and non-absorbable LS.

The Release of Albumin from PLGA and PCL Wafers Containing Natural and Synthetic Additives for Protein Delivery (단백질 전달체로서 천연 및 합성재료의 첨가에 따른 PLGA와 PCL웨이퍼로부터 알부민의 방출거동)

  • Hyun Hoon;Lee Jae Ho;Seo Kwang Su;Kim Moon Suk;Rhee Jhon M.;Lee Hai Bang;Khang Gilson
    • Polymer(Korea)
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    • v.29 no.5
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    • pp.468-474
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    • 2005
  • PLGA and PCL copolymers initiated by carbitol as drug carriers were synthesized by ring-opening polymerization of L-lactide (LA), glycolide (GA), and $\varepsilon-caprolactone(\varepsilon-CL)$. Implantable wafers were simply fabricated by direct compression method after physical mixing of copolymers and bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) as a model protein drug. The release amounts of BSA-FITC from wafers were determined by fluorescence intensity using the fluorescence spectrophotometer. Also, the release behavior of BSA-FITC on wafers was controlled by adding the additives such as collagen, small intestinal submucosa (SIS), poly(vinyl pyrrolidone) (PVP), and poly(thylene glycol) (PEG). The wafer prepared by PLGA and PCL exhibited slow release within $10\%$ for 30 days. But, those prepared by a variety of additives exhibited the controlled BSA release patterns with a dependence on the additive contents. furthermore, the wafers containing natural materials such as collagen and SIS showed more zero-order release profile than that with synthetic materials such as PVP and PEG. It was confirmed that the release of BSA from implantable wafers could be easily controlled by adding natural additives.

Genetic origin identification of Siberian chipmunks (Tamias sibiricus) in pet shops of South Korea

  • Lee, Seo-Jin;Jung, Gil-A;Min, Mi-Sook;Kim, Chuel-Kyu;Lee, Hang;Kim, Chang-Bae;Lee, Mu-Yeong
    • Animal cells and systems
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    • v.15 no.2
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    • pp.161-168
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    • 2011
  • Siberian chipmunks, Tamias sibiricus, are one of several popular companion animals found in the pet shops of South Korea. At present, however, there have been no studies done in South Korea examining their origin even though they could be potential carriers of zoonotic diseases, and are a species of concern for efficient conservation and management strategies. Sequences of the mitochondrial cytochrome b gene (1140 bp) were determined to investigate the origin of Siberian chipmunks sold in four South Korean pet shops through comparison with sequence data from animals of known locality. Nine Siberian chipmunks were collected from pet shops in South Korea, which resulted in nine haplotypes. One (AR) of these coincided with the haplotype previously described. Phylogenetic and network analyses using 53 haplotypes including 45 haplotypes from GenBank showed three phylogenetic groups in South Korea, almost concordant to locality, designated as northern, central, and southern parts as described in a previous study. Of the nine individuals examined from the pet shops, eight were clustered into the northern phylogroup but one (cgrb9153) was grouped with the southern phylogroup, implying that at least the Siberian chipmunks examined in this study did not originate from other countries. It is likely that most individuals sold in the pet shops of Seoul were caught in the wild in Gyeonggi-do and Gangwon-do, or are maternal descendants of captive-bred individuals originating from the northern part of South Korea. It is recommended that conservation and management units of Korean chipmunks should be examined in further detail.

In Vitro Stability of Liposomes Containing Newly Synthesized Glycolipid (신규 합성 당지질 함유 리포솜의 In Vitro 안정성)

  • Song, Chung-Kil;Jung, Soon-Hwa;Seong, Ha-Soo;Cho, Sun-Hang;Shin, Byung-Cheol
    • Journal of the Korean Chemical Society
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    • v.51 no.1
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    • pp.43-50
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    • 2007
  • Liposomes having particle size from several tens to hundreds nanometers are efficient carriers for injectable drug delivery. Enhancement of liposome stability in bloodstream has been studied because of its relatively short circulation time and fast clearance from human body by reticuloendothelial system (RES) in blood vessel. In this study, new disaccharide-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) derivatives in which lactose or sucrose as the disaccharide molecule was conjugated covalently to DSPE were synthesized. Liposomes of which surface had disaccharide molecules were prepared by incorporating the disaccharide-DSPE into liposomes as one of their lipid components. Particle size of the prepared liposomes was approximately 100 nm. The liposomes of which surface were modified with the disaccharide-DSPE showed -25 mV of zeta potential value due to the presence of hydroxyl groups on their surface, while the unmodified control liposomes showed -10 mV of zeta potential value. Loading efficiency of model drug, doxorubicin, into liposomes was about 90%. Stability of the disaccharide-modified liposomes in vitro was evaluated by monitoring the amount of protein adsorption and particle size of the liposomes in serum. Disaccharide-modified liposomes were more stable in serum than unmodified control liposomes or polyethyleneglycol (PEG)-modified liposomes due to less adsorption of serum protein and hence less increase of their particle size. The liposomes of which surface was modified with disaccharide-DSPE conjugate can be used as long-circulating carriers for drugs having high toxicity or short half-life time due to their enhanced stability in blood circulatory system.

Clinical review of Typhoid Fever Patients (장티브스에 관한 임상적 관찰)

  • 최정신
    • Journal of Korean Academy of Nursing
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    • v.6 no.1
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    • pp.60-71
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    • 1976
  • The author reviewed the medical records of 96 typhoid fever patients who were diagnosed, admitted, and treated at Sea grave Memorial Hospital from January 1 , 1973 through August 31, 1975. Diagnosis was determined by clinical observation, aerology and bacteriology, eighty patients were treated medically, the remaining 16 patients required surgical intervention. The following results were obtained: 1) The age distribution of the patients revealed that 33.3% wert between 10 and 19 years old 21.9% were between 20 and 29, and 19.8% were between 30 and 39. The majority of patients were from these more active age groups. Male to female sex ratio was 1.3 : 1 2) Seasonal distribution was observed. Most illness occurred in the summer and autumn month 5. 3) 84. 3%of the patients came from farm families. 4) Duration between onset and admission averaged 16.0 days. The group without compilations was admitted after an average of 15. 1 days; The group with complications was ad-matted after an average of 19.4 days. 5) Methods of treatment before admission were as follows: 10.4% at medical clinics, 61, 5% at pharmacies (antibiotics 47.9%, other. drugs 13.5%), 7.3% by herb medications, 20.8% had no treatment. 6) Main clinical symptoms were as follows: fever 93.8%, headache 47.9%, abdominal pain 47.9%, chills 38.5%, cough 36.5%, general weakness 26.0%, nausea e vomiting 24.0% and generalized pain 21.9%. 7) Temperature of patients on admission: 22.9% were 39f or more, 67.6% were between 37℃ and 38℃, and 9.4% were 37℃ or less. 8) Occurrence of intensional bleeding after onset of disease averaged 9.3 days; perforation occurred at an average of 19. 1 days. 9) Interval between onset of major complication and surgical intervention averaged 2.8 days. 10) Among the 68 patients who underwent the bacteriological test the positive rate was 44.1% (30). The positive ,ales to, each separate culture method were as follows: 20.4% in the blood culture, 40.4% in the stool culture and 6.7% in the urine culture. Among these bacteriological positive patients 15 patients had a negative results or less than 160 titer of vidal reaction. 11) The initial vidal test of the total group showed a counts of 160 titer or more in 60.4% and less than 160 titer in 39.6%, 12) W. B. C. Counts in the uncomplicated group indicated that 32.5% were 6,000/㎣ or less, 47.5% were between 6,000 and 10,000, arid 20.0% were 10,000/㎣ or more. In the complicated group, 37.6% were 6,000/㎣ or less, 25,0% were 6,000-10,000/㎣ and 37.6% were 10,000/㎣ or more. 13) Duration of hospital stay of the patients averaged 6.4 days in the uncomplicated group and 12.7 days in the complicated group. 14) Subdiaphragmatic free air simple X-ray was found in 91.7% of the perforated cases. 15) Duration of antibiotic therapy until an febrile state was attained averaged 4.8 days in the uncomplicated group and 6.5 days in the complicated group. 16) Operative procedures were as follows: one layer simple closure of their perforation with or without debasement in 56.3%, drainage only in 6.3%, small bowel resection with primary anastomosis in 18.8% , externalization in 6.3%, cholecystectomy in 6.3%, The clinical findings of this study suggest the following recommendations. According to Top's report; 1% of typhoid fever patients treated with chlorarnphenicol and 2% of patients treated with other drugs become chronic carriers. Therefore, importance should be given to the strict control of these carriers. Immunization, improvement of sanitation and living standards are all needed for the prevention and treatment of disease, but a more serious problem is a lack of knowledge on the part of patients and their families. Thus it is most urgent to enlighten the citizens about the transmission and hygiene related to contagious disease. Legal restriction of sale of antibiotics at drug stores without a physician's prescription is an urgent matter for public health administrators. An even more important nursing responsibility is the reemphasis on health education both in the clinical setting and in the home.

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Study of the enzymatic action of the chymopapain using pluronic based nano-carrier system on the cadaveric nucleus pulposus tissue (플루로닉(pluronic) 기반의 나노운반체(nano-carrier)에 충진된 카이모파파인(chymopapain)의 척추 추간판 조직내 작용성에 관한 연구)

  • Choi, Won Il;Tae, Gi Yoong;Hong, Young Ki
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.1
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    • pp.585-592
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    • 2015
  • The objective of this study is to determine if when chymopapain is loaded onto a nano-carrier, an injection of it reduces the spreading range of the drug within the discs. The materials for the experiment, which were conducted for three weeks, included fifteen intervertebral discs taken from two cadavers, which were divided according to the types of injected chymopapain solutions as follows: ordinary chymopapain group and nano-carrier system group. The nano-carrier system group was again divided into two subgroups according to the types of pluronics, the basic material for the nano-carriers: Pluronic F 127(DA-PF 127) in the nano-carrier group and Pluronic F 68(DA-PF 68) in the nano-carrier group. The results showed that the action of chymopapain using a pluronic-based nano-carrier system was localized around the center of the injection site instead of broad spreading, compared to that of the ordinary chymopapain group (p<0.01). This characteristic suggests a possible application to effective agents for minimally invasive spinal treatment through which disc lesions were removed selectively.

Characterization and Improvement of Dissolution Rate of Solid Dispersion of Celecoxib in PVP K30/Eudragit EPO (PVP K30/Eudragit EPO에 의한 셀레콕시브 고체분산체의 용출률 향상 및 특성)

  • Jeon, Dae Yeon;Jang, Ji Eun;Lee, Jeong Hwan;Yang, Jae Won;Park, Sang Mi;Lim, Dongkwon;Khang, Gilson
    • Polymer(Korea)
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    • v.38 no.4
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    • pp.434-440
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    • 2014
  • We prepared nanoparticles containing insoluble celecoxib by the method of solid dispersions using a spray dryer to improve solubility of celecoxib. We used PVP K30 and Eudragit EPO as water-soluble carriers for the solid dispersion, and poloxamer 407 as a surfactant. Characterization of celecoxib solid dispersion was performed by scanning electron microscope (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). The results of SEM, DSC and XRD demonstrated that celecoxib is amorphous in solid dispersion. The dissolution rate measured in intestinal juice showed that the method of solid dispersion improved celecoxib solubility as compared with a conventional drug (Celebres$^{(R)}$). In conclusion, solid dispersion formulation prepared by a spray dryer would improve the solubility of celecoxib in oral administration.