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1.
Int J Mol Sci ; 25(14)2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39062852

ABSTRACT

Therapeutic needs for hair loss are intended to find small interfering ribonucleic acid (siRNA) therapeutics for breakthrough. Since naked siRNA is restricted to meet a druggable target in clinic,, delivery systems are indispensable to overcome intrinsic and pathophysiological barriers, enhancing targetability and persistency to ensure safety, efficacy, and effectiveness. Diverse carriers repurposed from small molecules to siRNA can be systematically or locally employed in hair loss therapy, followed by the adoption of new compositions associated with structural and environmental modification. The siRNA delivery systems have been extensively studied via conjugation or nanoparticle formulation to improve their fate in vitro and in vivo. In this review, we introduce clinically tunable siRNA delivery systems for hair loss based on design principles, after analyzing clinical trials in hair loss and currently approved siRNA therapeutics. We further discuss a strategic research framework for optimized siRNA delivery in hair loss from the scientific perspective of clinical translation.


Subject(s)
Alopecia , RNA, Small Interfering , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , RNA, Small Interfering/therapeutic use , Humans , Alopecia/therapy , Alopecia/genetics , Animals , Nanoparticles/chemistry , Genetic Therapy/methods , Drug Delivery Systems/methods , Gene Transfer Techniques
2.
Pharm Dev Technol ; 23(4): 407-413, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29095656

ABSTRACT

Megestrol acetate (MGA) is used as a progestagen to treat advanced cancers in the breast or uterus and anorexia-cachexia syndrome in cancer patients. Due to its low solubility (BCS class II), MGA bioavailability needs to be enhanced for efficacy and safety. We developed MGA-encapsulated Eudragit® L100 (EUD) nanoparticles (MGA-EUD (1:1) and MGA-EUD (2:1)) using an ultrasonic nebulization method. MGA-EUD (1:1) and MGA-EUD (2:1) consisted of MGA and EUD at the mass ratios of 1:1 and 2:1. Their physicochemical properties, i.e. particle size, loading efficiency, morphology, and crystallinity were determined. Dissolution tests were performed using USP method II. For pharmacokinetics, they were orally administered at 50 mg/kg to mice. Microcrystalline MGA suspension (MGA-MC, Megace®, BMS) was used as control. MGA-EUD (1:1) and MGA-EUD (2:1) had a smooth and spherical shape of 0.70 and 1.05 µm in diameter with loading efficiencies of 93 and 95% showing amorphous states of MGA. They significantly enhanced the dissolution potential of MGA. Oral bioavailability of MGA-EUD (1:1) and MGA-EUD (2:1) increased 2.0- and 1.7-fold compared to that of MGA-MC. It suggests that ultrasonic nebulization method for the fabrication of polymeric nanoparticles is a promising approach to improve the bioavailability of poorly soluble drugs.


Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Appetite Stimulants/administration & dosage , Megestrol Acetate/administration & dosage , Nanoparticles/chemistry , Polymethacrylic Acids/chemistry , Administration, Oral , Animals , Antineoplastic Agents, Hormonal/chemistry , Antineoplastic Agents, Hormonal/pharmacokinetics , Appetite Stimulants/chemistry , Appetite Stimulants/pharmacokinetics , Biological Availability , Male , Megestrol Acetate/chemistry , Megestrol Acetate/pharmacokinetics , Mice , Mice, Inbred BALB C , Particle Size , Phase Transition , Solubility , Sonication , Suspensions , Ultrasonics
3.
Biomed Chromatogr ; 28(11): 1565-87, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25294385

ABSTRACT

Third-generation cephalosporins are semi-synthetic antibiotics with enhanced activity against Gram-negative organisms. The cephalosporins in biological samples are mostly determined using high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS/MS). In recent years, numerous bioanalytical methods have been developed to improve the sensitivity and specificity of cephalosporin quantification using the powerful LC-MS/MS systems that are common in research laboratories. This review article presents recently developed bioanalytical methods by HPLC or LC-MS(/MS) for 12 third-generation cephalosporins, including five oral third-generation cephalosporins, and further discusses their application in pharmacokinetic studies of animals and humans.


Subject(s)
Cephalosporins/analysis , Cephalosporins/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Animals , Cephalosporins/chemistry , Humans
4.
Front Pharmacol ; 15: 1434961, 2024.
Article in English | MEDLINE | ID: mdl-39221145

ABSTRACT

Therapeutic antibodies (Abs) have been anticipated as promising alternatives to conventional treatments such as topical minoxidil and oral finasteride for androgenetic alopecia (AGA). Due to the high molecular weight of typical Abs, the half-life of subcutaneous Abs exceeds 2 weeks, allowing an administration intervals of once a month or longer. Direct injection into the areas of hair loss is also feasible, potentially enhancing treatment efficacy while minimizing systemic side effects. However, therapeutic Abs are rarely developed for AGA therapy due to the requirement to be responsiveness to androgens and to exist in the extracellular fluid or cell surface surrounding the hair follicle. In this review, we introduce recent progress of antibody therapeutics in AGA targeting the prolactin receptor, Interleukin-6 receptor, C-X-C motif chemokine ligand 12, and dickkopf 1. As therapeutic Abs for AGA are still in the early stages, targets need further validation and optimization for clinical application.

5.
J Pharm Pharm Sci ; 15(3): 467-82, 2012.
Article in English | MEDLINE | ID: mdl-22974792

ABSTRACT

PURPOSE: Long-term stable cationic solid lipid nanoparticles (cSLNs) were formulated to transfer SMAD3 antisense oligonucleotides (ASOs) into the cells to enhance the intracellular activity of the ASOs. The SMAD3 ASOs were designed to block the inflammatory processes linked to TGFß/SMAD3 pathway. METHODS: The cSLN formulation was prepared by high-pressure homogenization method composed of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), dioleoylphosphoethanolamine (DOPE), Tween 20, and tricaprin as a solid lipid core (1:1:1:1.67, w/w). The size and the zeta potential of the prepared cSLNs were measured by light scattering. The cSLN/ASO complexes were generated and introduced into the murine macrophage cells. After the treatment of the complexes, the cellular uptake of the complexes was determined by flow cytometry and the intracellular activity of SMAD3 ASOs from the complexes was evaluated by western blotting of SMAD3. In addition, TGFß1, an upstream molecule of TGFß/SMAD3 pathway, was monitored by ELISA. RESULTS: The nano-scale sized cSLNs were positively charged and physically stable at 4oC during the storage up to 24 months. The uptake efficiency of the cSLN/ASO complexes into macrophage cells was enhanced up to 80% without cytotoxicity. After the treatment of the cSLN/ASO complexes, SMAD3 as well as TGFß1 was significantly suppressed based on the SMAD3 ASO activity in the macrophage cells. In addition, the cSLN/ASO complexes prevented the morphological change to dendritic shape in the activated macrophage cells. CONCLUSION: These results suggest that the cSLNs have a potential to deliver the SMAD3 ASOs to intracellular compartments for the anti-inflammatory effect. The development of this strategy might lead to anti-inflammatory and anti-fibrotic therapies in immunological disorders.


Subject(s)
Drug Carriers/administration & dosage , Macrophages/metabolism , Nanoparticles/administration & dosage , Oligonucleotides, Antisense/administration & dosage , Smad3 Protein/genetics , Animals , Cell Line , Drug Carriers/chemistry , Fatty Acids, Monounsaturated/chemistry , Macrophages/drug effects , Mice , NIH 3T3 Cells , Nanoparticles/chemistry , Oligonucleotides, Antisense/chemistry , Phosphatidylethanolamines/chemistry , Quaternary Ammonium Compounds/chemistry , Transforming Growth Factor beta1/metabolism
6.
Data Brief ; 42: 108137, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35496475

ABSTRACT

Zinc oxide (ZnO) nanoparticles (NPs) have been applied as high-performance intelligent materials to create a hierarchical multimodal-porous architectures for application in biomedical research fields [1]. They were microfluidically synthesized via dual-step nanofabrication compared to the conventional particles including ZnO NPs synthesized at single-pot macroscale, nanosized ZnO, and hybrid ZnO. The physicochemical properties were characterized, including morphology, particle size distribution, atomic composition, crystallinity, purity, reactant viscosity, surface charge, photocatalysis, photoluminescence, and porosity. A hierarchical multimodal-porous three-dimensional (3D) architecture of ZnO NPs was generated and optimized on the solid plate substrate of cellulose paper sheet after solvent evaporation. The dataset provides the nanomaterial design and architecture generation of ZnO NPs, explaining multi-physics phenomena in association with performance optimization processes.

7.
Bioconjug Chem ; 22(3): 466-74, 2011 Mar 16.
Article in English | MEDLINE | ID: mdl-21344902

ABSTRACT

Although bioactive polymers such as cationic polymers have demonstrated potential as drug carriers and nonviral gene delivery vectors, high toxicity and uncontrolled, instantaneous cellular interactions of those vectors have hindered the successful implementation In Vivo. Fine control over the cellular interactions of a potential drug/gene delivery vector would be thus desirable. Herein, we have designed nanohybrid systems (100-150 nm in diameter) that combine the polycations with protective outer layers consisting of biodegradable polymeric nanoparticles (NPs) or liposomes. A commonly used polycation polyethylenimine (PEI) was employed after conjugation with rhodamine (RITC). The PEI-RITC conjugates were then encapsulated into (i) polymeric NPs made of either poly(lactide-co-glycolide) (PLGA) or poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA); or (ii) PEGylated liposomes, resulting in three nanohybrid systems. Through the nanohybridization, both cellular uptake and cytotoxicity of the nanohybrids were kinetically controlled. The cytotoxicity assay using MCF-7 cells revealed that liposome-based nanohybrids exhibited the least toxicity, followed by PEG-PLGA- and PLGA-based NPs after 24 h incubation. The different kinetics of cellular uptake was also observed, the liposome-based systems being the fastest and PLGA-based systems being the slowest. The results present a potential delivery platform with enhanced control over its biological interaction kinetics and passive targeting capability through size control.


Subject(s)
Liposomes/chemistry , Liposomes/metabolism , Nanoparticles/chemistry , Polymers/chemistry , Biological Transport , Cell Line, Tumor , Humans , Kinetics , Liposomes/pharmacokinetics , Liposomes/toxicity , Nanoparticles/toxicity , Rhodamines/chemistry
8.
Nanomaterials (Basel) ; 11(2)2021 Jan 20.
Article in English | MEDLINE | ID: mdl-33498491

ABSTRACT

Zinc oxide (ZnO) nano/microparticles (NPs/MPs) have been studied as antibiotics to enhance antimicrobial activity against pathogenic bacteria and viruses with or without antibiotic resistance. They have unique physicochemical characteristics that can affect biological and toxicological responses in microorganisms. Metal ion release, particle adsorption, and reactive oxygen species generation are the main mechanisms underlying their antimicrobial action. In this review, we describe the physicochemical characteristics of ZnO NPs/MPs related to biological and toxicological effects and discuss the recent findings of the antimicrobial activity of ZnO NPs/MPs and their combinations with other materials against pathogenic microorganisms. Current biomedical applications of ZnO NPs/MPs and combinations with other materials are also presented. This review will provide the better understanding of ZnO NPs/MPs as antibiotic alternatives and aid in further development of antibiotic agents for industrial and clinical applications.

9.
Pharmaceutics ; 13(2)2021 Feb 06.
Article in English | MEDLINE | ID: mdl-33561936

ABSTRACT

Antimicrobial activity of multiscale metal oxide (MO) particles against Escherichia coli (E. coli) and M13 bacteriophage (phage) was investigated under dual ultraviolet (UV) irradiation. Zinc oxide (ZnO), magnesium oxide (MgO), cuprous oxide (Cu2O), and cupric oxide (CuO) were selected as photocatalytic antimicrobials in MO particles. Physicochemical properties including morphology, particle size/particle size distribution, atomic composition, crystallinity, and porosity were evaluated. Under UV-A and UV-C irradiation with differential UV-C intensities, the antimicrobial activity of MO particles was monitored in E. coli and phage. MO particles had nano-, micro- and nano- to microscale sizes with irregular shapes, composed of atoms as ratios of chemical formulae and presented crystallinity as pure materials. They had wide-range specific surface area levels of 0.40-46.34 m2/g. MO particles themselves showed antibacterial activity against E. coli, which was the highest among the ZnO particles. However, no viral inactivation by MO particles occurred in phage. Under dual UV irradiation, multiscale ZnO and CuO particles had superior antimicrobial activities against E. coli and phage, as mixtures of nano- and microparticles for enhanced photocatalytic antimicrobials. The results showed that the dual UV-multiscale MO particle hybrids exhibit enhanced antibiotic potentials. It can also be applied as a next-generation antibiotic tool in industrial and clinical fields.

10.
Food Chem ; 325: 126751, 2020 Apr 04.
Article in English | MEDLINE | ID: mdl-32387941

ABSTRACT

Mass-produced Spirulina powder was characterized based on biomarkers for quality assessment. Other Spirulina powder products for functional foods and animal feeds were used as controls. In this study, Spirulina platensis was mass-cultured in modified Spirulina medium using a dispersive two-ton scale reactor for 30 days. After processing, the Spirulina powder was evaluated using FE-SEM and XPS. In the extracts, chlorophylls were determined using TLC and Q-TOF. SDS-PAGE and DSC were used to analyze protein biomarkers and to monitor thermal stability. The powder presented a microscale distorted sphere. Zinc, iron and calcium were detected on the powder surface. In the extracts, chlorophylls-a, -b, and -c, allophycocyanin, and phycocyanin-C were detected. Despite the similar morphology of all Spirulina products, the mass-produced Spirulina powder showed prolonged protein stability in biochemical compositions. The results suggest that mass-produced Spirulina powder can be characterized using biomarker-based advanced techniques. This protocol can be extended to other microalgae.

11.
Mater Sci Eng C Mater Biol Appl ; 115: 110843, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32600674

ABSTRACT

Transition metal-doped titanium dioxide nanoparticles (M-TiO2 NPs) have been studied to enhance the activity of TiO2 NPs in biomedical applications. In this study, in vitro and in vivo toxicological aspects of M-TiO2 NPs were reported to assess the safety of these materials. M-TiO2 NPs were synthesized via a photo-deposition technique. Nickel (Ni) and platinum (Pt) were used as dopants. Physicochemical properties, cytotoxicity, phototoxicity, gene ontology (GO) and dermal toxicity of M-TiO2 NPs were investigated. Ni-TiO2 (Ni, 1.02%) and Pt-TiO2 (Pt, 0.26%) NPs were sphere shape crystals with nanoscale size. ARPE-19 cells were more susceptible to Pt-TiO2 NPs (EC50, 0.796 mg/mL) than Ni-TiO2 NPs (EC50, 2.945 mg/mL). M-TiO2 NPs were rated as probably phototoxic to phototoxic. GO suggested binding function and metabolic processes as a risk mechanism of M-TiO2 NPs. In vivo toxicological effects of Ni-TiO2 NPs were not observed on body weight, serum aspartate transaminase/alanine transaminase levels, and skin histology at 61.5-6150 mg/kg. Specifically, skin thickness was not significantly modified (max. 33.2 ± 8.7 µm) and inflammation grade was less than level 2 (max. 1.2 ± 0.4). From these results, Ni-TiO2 and Pt-TiO2 NPs show promise as enhanced photocatalysts for safe and sustainable usage.


Subject(s)
Nickel/chemistry , Platinum/chemistry , Skin/drug effects , Titanium/pharmacology , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Cell Line , Cell Survival/drug effects , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Mice , Models, Animal , Titanium/chemistry , Toxicity Tests
12.
J Gene Med ; 11(1): 26-37, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19006098

ABSTRACT

BACKGROUND: Interleukin (IL)-13, overproduced in the skin of atopic dermatitis (AD), has been shown to play an essential role in the pathogenesis of the disease. Thus, inhibition of IL-13 production should provide a key step to alleviate disease conditions of the atopic skin. In the present study, IL-13 antisense oligonucleotide (ASO) was designed and formulated with cationic elastic liposome (cEL) to improve transdermal delivery. METHODS: ASOs were generated against murine IL-13 mRNA (+4 to + 23) and complexed with cEL. Physicochemical properties of IL-13 ASO/cEL complex were examined by DNA retardation and DNase I protection assay. An in vitro inhibition study was performed in T-helper 2 (Th2) cells and cytotoxicity was tested by the XTT assay. The in vivo effect of IL-13 ASO/cEL complex was tested in a murine model of AD. RESULTS: In vitro, the IL-13 ASO/cEL complex showed dose- and ratio-dependent inhibition of IL-13 secretion in Th2 cells. At the IL-13 ASO/cEL ratio of 6, maximum inhibition of IL-13 secretion was observed. When applied to the ovalbumin-sensitized murine model of AD, topically administered IL-13 ASO/cEL complex dramatically suppressed IL-13 production (by up to 70% of the control) in the affected skin region. In addition, the levels of IL-4 and IL-5 were also significantly reduced. Moreover, IL-13 ASO/cEL-treated AD mice showed reduced infiltration of inflammatory cells into the epidermal and dermal areas, with concomitant reduction of skin thickness. CONCLUSIONS: These data suggests that IL-13 ASO/cEL complex can provide a potential therapeutic tool for the treatment of AD and also be applied to other immune diseases associated with the production of Il-13.


Subject(s)
Dermatitis, Atopic/drug therapy , Interleukin-13/antagonists & inhibitors , Liposomes/chemistry , Oligonucleotides, Antisense/administration & dosage , Administration, Topical , Animals , Dermatitis, Atopic/immunology , Humans , Interleukin-13/genetics , Interleukin-4/immunology , Interleukin-5/immunology , Mice , Mice, Inbred BALB C , NIH 3T3 Cells , Tumor Cells, Cultured
13.
Pharmacol Res ; 60(1): 57-60, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19427587

ABSTRACT

We investigated the pharmacokinetics of 2 microg calcitriol in eight healthy human after a single oral administration. Plasma calcitriol was analyzed by sensitive and quantitative enzyme immunoassay following intra- and inter-day validation. In subjects, AUC(0-infinity) and AUC(0-24h) were 267 and 246 pg h ml(-1), respectively. Although the mean plasma concentration of calcitriol in human subjects did not return to baseline at 24h post-dosing, the mean ratio of AUC(0-24h) to AUC(0-infinity) was greater than 80%. The C(max) of calcitriol was measured at 3.4h after administration as 50.0 pg ml(-1). From our results, it can offer new opportunities to design and determine individually appropriate therapeutic dosage regimens based on a pharmacokinetic profile and be used for bioequivalence and reevaluation study of generic drug.


Subject(s)
Calcitriol/blood , Calcitriol/pharmacokinetics , Administration, Oral , Adult , Area Under Curve , Blood Pressure/drug effects , Calcitriol/administration & dosage , Calcitriol/adverse effects , Calcium/blood , Dose-Response Relationship, Drug , Heart Rate/drug effects , Humans , Immunoenzyme Techniques , Phosphates/blood , Reproducibility of Results , Young Adult
14.
Pharmaceutics ; 11(11)2019 Nov 04.
Article in English | MEDLINE | ID: mdl-31689932

ABSTRACT

Zinc oxide (ZnO) nanoparticles have been studied as metal-based drugs that may be used for biomedical applications due to the fact of their biocompatibility. Their physicochemical properties, which depend on synthesis techniques involving physical, chemical, biological, and microfluidic reactor methods affect biological activity in vitro and in vivo. Advanced tool-based physicochemical characterization is required to identify the biological and toxicological effects of ZnO nanoparticles. These nanoparticles have variable morphologies and can be molded into three-dimensional structures to enhance their performance. Zinc oxide nanoparticles have shown therapeutic activity against cancer, diabetes, microbial infection, and inflammation. They have also shown the potential to aid in wound healing and can be used for imaging tools and sensors. In this review, we discuss the synthesis techniques, physicochemical characteristics, evaluation tools, techniques used to generate three-dimensional structures, and the various biomedical applications of ZnO nanoparticles.

15.
Int J Nanomedicine ; 14: 1737-1751, 2019.
Article in English | MEDLINE | ID: mdl-30880977

ABSTRACT

BACKGROUND: Zinc oxide (ZnO) nanoparticles and their networks have been developed for use in various applications such as gas sensors and semiconductors. AIM: In this study, their antibacterial activity against Escherichia coli under dual ultraviolet (UV) irradiation for disinfection was investigated. MATERIALS AND METHODS: ZnO nanoparticles were synthesized and immobilized onto silicon (Si) wafers by self-assembly. The physicochemical properties and antibacterial activity of ZnO nanoparticles and their networks were evaluated. Gene ontology was analyzed and toxicity levels were also monitored. RESULTS: Synthesized ZnO nanoparticles were spherical nanocrystals (<100 nm; Zn, 47%; O, 53%) that formed macro-mesoporous three-dimensional nanostructures on Si wafers in a concentration-dependent manner. ZnO nanoparticles and their networks on Si wafers had an excellent antibacterial activity against E. coli under dual UV irradiation (>3log CFU/mL). Specifically, arrayed ZnO nanoparticle networks showed superior activity compared with free synthesized ZnO nanoparticles. Oxidative stress-responsive proteins in E. coli were identified and categorized, which indicated antibacterial activity. Synthesized ZnO nanoparticles were less cytotoxic in HaCaT with an IC50 of 6.632 mg/mL, but phototoxic in Balb/c 3T3. CONCLUSION: The results suggested that ZnO nanoparticles and their networks can be promising photocatalytic antibiotics for use in next-generation disinfection systems. Their application could also be extended to industrial and clinical use as effective and safe photocatalytic antibiotics.


Subject(s)
Anti-Bacterial Agents/pharmacology , Disinfection/methods , Nanoparticles/chemistry , Ultraviolet Rays , Zinc Oxide/pharmacology , Catalysis , Cell Line , Crystallization , Escherichia coli/drug effects , Escherichia coli/radiation effects , Eye/cytology , Humans , Microbial Sensitivity Tests , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Particle Size , Silicon/pharmacology , Skin/cytology , Zinc Oxide/toxicity
16.
Eur J Pharm Biopharm ; 68(3): 545-54, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17881199

ABSTRACT

Mutations in the p53 tumor suppressor gene are the most common molecular genetic abnormalities to be described in lung cancer. However, there have been few reports of nonviral vector-mediated p53 gene delivery in lung cancer. A new formulation of cationic solid lipid nanoparticles (SLNs) for gene delivery was produced by the melt homogenization method with slight modification, and the SLNs were formulated by mixing tricaprin (TC) as a core, 3beta[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol), dioleoylphosphatidylethanolamine (DOPE) and Tween 80 in various ratios. Plasmid DNA (pp53-EGFP)/SLNs complexes were transfected into human non-small cell lung cancer cells (H1299 cells) and transfection efficiency was determined by FACS analysis. The gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. The cellular growth inhibition and apoptosis of treated cells with pp53-EGFP/SLNs complexes were assessed by trypan blue exclusion assay and annexin V staining, respectively. In vivo biodistribution of plasmid DNA was investigated by PCR and RT-PCR. The transfection efficiency of SLN1 (TC:DC-Chol:DOPE:Tween 80=0.3:0.3:0.3:1), which showed the highest transfection efficiency among the SLN formulations, was higher than that of commercially available Lipofectin. The SLNs-mediated transfection of the p53 gene resulted in efficient high levels of wild-type p53 mRNA and protein expression levels in H1299 cells. The efficient reestablishment of wild-type p53 function in lung cancer cells restored the apoptotic pathway. Taken together, our results reveal that cationic SLN-mediated p53 gene delivery may have potential for clinical application as a nonviral vector-mediated lung cancer therapy due to its effective induction of apoptosis and tumor growth inhibition.


Subject(s)
Gene Transfer Techniques , Genes, p53 , Genetic Therapy , Lipids/administration & dosage , Lung Neoplasms/therapy , Nanoparticles/administration & dosage , Animals , Apoptosis , Cell Line, Tumor , Freeze Drying , Humans , Lipids/chemistry , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Particle Size , Plasmids , Tissue Distribution
17.
Invest Ophthalmol Vis Sci ; 48(2): 699-704, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17251468

ABSTRACT

PURPOSE: To determine the usefulness of slow-releasing tranilast in polytetrafluoroethylene/polylactide-co-glycolide (PTFE/PLGA) laminate for delayed adjustable strabismus surgery. METHODS: A prospective, masked-observer, controlled study was performed in 25 rabbits. Fifty rabbit eyes were divided randomly into three groups. After a recession of the superior rectus muscle (SRM), a PTFE/PLGA laminate containing tranilast, PTFE alone, or balanced salt solution was applied beneath and over the SRM in the PTFE/PLGA-tranilast group (group P-T), the PTFE group (group P), and the control group, respectively. Delayed adjustment was performed by a masked observer once on each SRM 3 or 5 weeks after surgery. Adjustability, adjustment lengths, forces required, and adhesion degrees were evaluated. RESULTS: In the control group, adjustment was impossible in any eye 3 or 5 weeks after surgery. In group P, adjustment was possible in 5 of 8 eyes 3 weeks after surgery and in 5 of 10 eyes 5 weeks after surgery. In group P-T, adjustment was possible in 8 of 10 eyes 3 and 5 weeks after surgery. On comparing adjustability, a significant difference was observed between group P-T and the control group 3 and 5 weeks after surgery (P = 0.006, P = 0.006, respectively). A significant difference was observed between group P-T and the control group (P = 0.016) in terms of adhesion between SRMs and conjunctivae 5 weeks after surgery. CONCLUSIONS: Slow-releasing tranilast in PTFE/PLGA was found to reduce adhesion and allowed delayed adjustment in most eyes for up to 5 weeks after surgery.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Lactic Acid , Polyglycolic Acid , Polymers , Polytetrafluoroethylene , Postoperative Complications/prevention & control , Strabismus/surgery , Suture Techniques , ortho-Aminobenzoates/administration & dosage , Animals , Delayed-Action Preparations , Drug Carriers , Models, Animal , Oculomotor Muscles/drug effects , Oculomotor Muscles/pathology , Polylactic Acid-Polyglycolic Acid Copolymer , Prospective Studies , Rabbits , Sclera/drug effects , Sclera/pathology , Tissue Adhesions/prevention & control
18.
Int J Pharm ; 528(1-2): 172-179, 2017 Aug 07.
Article in English | MEDLINE | ID: mdl-28549974

ABSTRACT

Tacrolimus sorption to tubes was evaluated using pump and drip methods For tubes, polyvinylchloride (PVC)- and non-PVC-based (polyurethane [PU] and polyolefin [PO]) tubes were used. First, inner surface properties of tubes were analyzed using field emission scanning electron microscopy and X-ray photoelectron spectroscopy. Tacrolimus was quantitatively analyzed using high-performance liquid chromatography with UV detection. For kinetic sorption analysis, diluted tacrolimus to 10µg/mL was passed through 1-m-long tubes at 10mL/h. Samples were collected at 1-4h. The inner surface of PO-based tubes was relatively smooth and soft compared with those of PVC- and PU-based tubes. Atomic compositions of tubes matched chemical formulas of polymers excluding low-level impurity in PVC-based tubes. Tacrolimus was successfully analyzed and linearly determined at 2.5-20µg/mL. From both methods, PVC- and PO-based tubes exhibited the highest and the lowest (<10%) sorption levels to tacrolimus, respectively. Tacrolimus was stably delivered using the pump method. Results suggested that the pump method can estimate tacrolimus sorption in administration set tubes and evaluate other sorptional drugs used at low concentrations. PO-based tubes also have promising potential as an alternative for administration set tubes.


Subject(s)
Polyurethanes/chemistry , Polyvinyl Chloride/chemistry , Tacrolimus/chemistry , Photoelectron Spectroscopy , Polymers
19.
Int J Nanomedicine ; 12: 8057-8070, 2017.
Article in English | MEDLINE | ID: mdl-29138562

ABSTRACT

Metal oxide (MO) nanoparticles have been studied as nano-antibiotics due to their antimicrobial activities even in antibiotic-resistant microorganisms. We hypothesized that a hybrid system of dual UV irradiation and MO nanoparticles would have enhanced antimicrobial activities compared with UV or MO nanoparticles alone. In this study, nanoparticles of ZnO, ZnTiO3, MgO, and CuO were selected as model nanoparticles. A dual UV collimated beam device of UV-A and UV-C was developed depending upon the lamp divided by coating. Physicochemical properties of MO nanoparticles were determined using powder X-ray diffractometry (PXRD), Brunauer-Emmett-Teller analysis, and field emission-scanning electron microscopy with energy-dispersive X-ray spectroscopy. Atomic force microscopy with an electrostatic force microscopy mode was used to confirm the surface topology and electrostatic characteristics after dual UV irradiation. For antimicrobial activity test, MO nanoparticles under dual UV irradiation were applied to Escherichia coli and M13 bacteriophage (phage). The UV-A and UV-C showed differential intensities in the coated and uncoated areas (UV-A, coated = uncoated; UV-C, coated ≪ uncoated). MO nanoparticles showed sharp peaks in PXRD patterns, matched to pure materials. Their primary particle sizes were less than 100 nm with irregular shapes, which had an 8.6~25.6 m2/g of specific surface area with mesopores of 22~262 nm. The electrostatic properties of MO nanoparticles were modulated after UV irradiation. ZnO, MgO, and CuO nanoparticles, except ZnTiO3 nanoparticles, showed antibacterial effects on E. coli. Antimicrobial effects on E. coli and phages were also enhanced after cyclic exposure of dual UV and MO nanoparticle treatment using the uncoated area, except ZnO nanoparticles. Our results demonstrate that dual UV-MO nanoparticle hybrid system has a potential for disinfection. We anticipate that it can be developed as a next-generation disinfection system in pharmaceutical industries and water purification systems.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteriophage M13/drug effects , Escherichia coli/drug effects , Escherichia coli/radiation effects , Metal Nanoparticles/chemistry , Anti-Infective Agents/chemistry , Bacteriophage M13/radiation effects , Metal Nanoparticles/administration & dosage , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Particle Size , Spectrometry, X-Ray Emission , Static Electricity , Ultraviolet Rays , X-Ray Diffraction , Zinc Oxide/chemistry , Zinc Oxide/pharmacology
20.
J Vis Exp ; (121)2017 03 11.
Article in English | MEDLINE | ID: mdl-28362410

ABSTRACT

Administration sets are delivery tools for the direct application of drugs into the body and are composed of a spike, a drip chamber, tubes, Luer adapters (connectors), a needle cover for protection, and other accessories. Drug sorption to tubes of administration sets is a critical issue in terms of safety and efficacy. Although drug sorption is an important factor in the quality of an administration set, there are no standard evaluation methods for the regulation of drug sorption to the tubes. Here, we describe an evaluation protocol for drug sorption to tubes of administration sets. Tubes made of polyvinyl chloride (PVC)- and non-PVC-based polymeric materials were cut to 1 m in length. Diazepam and tacrolimus were used as model drugs. In the kinetic sorption study, we selected the drug concentration and flow rate based on the clinical usage of these drugs. After the dilution of each drug in a glass bottle, the diluted drug solution was delivered through tubes of administration sets using a pump. Samples were collected in amber vials at appropriate time points and the drugs were analyzed using high-performance liquid chromatography. Drug concentrations and sorption levels to tubes of the administration sets were calculated. Acceptable criteria to ensure the quality of administration sets are recommended.


Subject(s)
Pharmaceutical Preparations/chemistry , Polyvinyl Chloride/chemistry , Adsorption , Chromatography, High Pressure Liquid , Diazepam/analysis , Diazepam/chemistry , Drug Administration Routes , Equipment Design , Pharmaceutical Preparations/analysis , Tacrolimus/analysis , Tacrolimus/chemistry
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