• Biomedical Science Letters
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• v.29 no.4
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• pp.231-241
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• 2023

Messenger RNA (mRNA)-based vaccines and treatments have recently emerged as a promising strategy. Naked mRNA presents various limitations for direct delivery. Therefore, in this paper, Lipid Nanoparticles (LNPs) were utilized for the delivery of mRNA. Lipid nanoparticle (LNP) mRNA systems are highly effective as vaccines, but their efficacy for pulmonary delivery has not yet been fully established. Additionally, research on effective delivery systems and administration methods for vaccines is required to resolve the stability and degradation issues associated with naked mRNA delivery. This study aimed to determine mRNA delivery efficiency via the inhalation of a lipid nanoparticle (LNP) formulation designed specifically for pulmonary delivery. To this purpose, we built a library of seven LNP configurations with different lipid molar and N/P ratios and evaluated their encapsulation efficiency using gel retardation assay. Among the tested LNPs, LNP1, LNP2-2, and LNP3-2 demonstrated high transfection efficiency in vitro based on FACS analyses luciferase assays, and intracellular accumulation tests. The mRNA delivery efficiencies of the selected LNPs after inhalation and intravenous injection were compared and evaluated. LNP2-2 showed the highest mRNA expression in healthy mouse lungs when aerosolized and was found to be non-toxic. These results indicate that LNP2-2 is a promising carrier for lung mRNA delivery via inhalation.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.167-172
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• 2001

All-trans retinoic acid (ATRA), vitamin A acid, has been shown to exert anticancer activity in a number of types of cancers, particularly in acute promyelocytic leukaemia (APL). Due to its highly variable bioavailability and induction of its own metabolism after oral treatment, development of parenteral dosage forms are required. However, its poor aqueous solubility and chemical unstability give major drawbacks in parenteral administration. This study was undertaken to investigate a possibility to develop a parenteral formulation of ATRA by employing solid lipid nanoparticle (SLN) as a carrier. By optimizing the production parameters and the composition of SLNs, SLNs with desired mean particle size (<100 nm) as a parenteral dosage form could be produced from trimyristin (as solid lipid), Egg phosphatidylcholine and Tween 80 (as SLN stabilizer). The mean particle size of SLN formulation of ATRA was not changed during storage, suggesting its physical stability. Thermal analysis confirmed that the inner lipid core of SLNs exist at solid state. The mean particle size of ATRA-loaded SLNs was not significantly changed by the lyophilization process. ATRA could be efficiently loaded in SLNs, while maintaining its anticancer activity against HL-60, a well-known APL cell line. Furthermore, by lyophilization, ATRA loaded in SLN could be retained chemically stable during storage. Taken together, our present study demonstrates that physically and chemically stable ATRA formulation adequate for parenteral administration could be obtained by employing SLN technology.

• Journal of Biomedical Engineering Research
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• v.39 no.4
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• pp.147-152
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• 2018

Lung cancer and pulmonary metastasis are the leading cause of cancer mortality worldwide. Survival for patients with lung metastases is about 5%. Nanoparticles have been developed for the imaging and treatment of various cancers, including pulmonary malignancies. In this work, we report lipid coated polymeric nanoparticles (LPNs) with an average diameter of 154 nm. In vivo performance of LPNs was characterized using optical imaging system. We expect this nanoparticle can be used for finding lung cancer or lung metastasis. Eventually loading therapeutic drug with the nanoparticle will be utilized for cancer diagnosis and effective therapy at the same time.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.373-378
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• 2010

In order to develop a topical preparation which has a high occlusive property with skin moisturization, nano-structured lipid carrier (NLC) systems along with solid lipid nanoparticle (SLN) were designed. Various NLC dispersions were successfully formulated with Compritol 888 ATO as a solid lipid, Labrafil M 1944 CS as an oil, and Tween 80 as a surfactant. The increase of oil content (5 to 50%) led to the decrease in the occlusion factor in the order of SLN > NLC-5 > NLC-15 = NLC-30 > NLC-50. Particle size of lipid particulates was in the range of 100 to 160 nm. NLC-based carbogels were prepared by the employment of humectants such as urea, glycerin, and Tinocare GL to carbomer gel. NLC-30 gel formulations containing 4 or 8 % of lipid particles showed improved occlusive effect in vitro, compared to NLC-free gel base. Even though NLC-free gel base revealed comparable occlusion effect by itself, the occlusion factor of 4 % NLC-30 gel was about 2-fold higher than that of NLC-free gel base.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.249-255
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• 1998

Solid Lipid Nanoparticle(SLN), one of the colloidal carrier systems, has many advantages such as good biocompatibility, low toxicity and stability. In this paper, the effects of drug lipophilicity and surfactant on the drug loading capacity, particle size and drug release profile were examined. SLNs were prepared by homogenization of melted lipid dispersed in an aqueous surfactant solution. Ketoprofen, ibuprofen and pranoprofen were used as model drugs and tweens and poloxamers were tested for the effect of surfactant. Mean particle size of prepared SLNs was ranged from 100 to 150nm. The drug loading capacity was improved with the most lipophilic drug and low concentration of surfactant. Particle size and polydispersity of SLNs were changed according to the used lipid and surfactant. The rates of drug release were controlled by the loading drug and surfactant concentration. SLN system with effective drug loading efficiency and proper particle size for the intravenous or oral formulation can be prepared by selecting optimum drug and surfactant.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.125-135
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• 1996

Solid lipid nanoparticles(SLN) are particulate systems for parenteral drug administration and suitable for controlled release. SLN were prepared by homogenization process. Dispersion at increased temperature (molten lipid) was performed to yield SLN loaded with lipophilic drugs. Tetracaine base, lidocaine base, prednisolone, methyltestosterone and ethinylestradiol were used as model drugs to access the loading capacity and to study the release behavior. To investigate production parameters(lipids, surfactant concentration, homogenizing rpm) in the formation of SLN, particle size was performed by laser diffraction analysis. The mean particle size of SLN with stearic acid or trilaurin was below 1 micron. By decreasing the particle size and increasing the surfactant concentration, the release rate was increased especially in the case of highly lipophilic drug loaded SLN. Methyltestosterone or ethinylestradiol loaded SLN showed a distinctly prolonged release over a few days.

• Macromolecular Research
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• v.15 no.6
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• pp.547-552
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• 2007

Water soluble polymer, poly(vinyl pyrrolidone) was chosen to conjugate with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) (N-succinyl DPPE) to make a new drug delivery system. PVP with an amine group (amino-PVP) was polymerized by free radical polymerization. The amine group of amino-PVP was conjugated with the carboxylic group of N-succinyl DPPE. The resultant conjugate could form nanoparticles in the aqueous solution; these nanoparticles were termed a lipid-polymer system. The critical aggregation concentration was measured with pyrene to give a value of $1{\times}10^{-3}g/L$. The particle size of the lipid-polymer system, as measured by DLS, AFM and TEM, was about 70 nm. Lipophilic component in the inner part of the lipid-polymer system could derive the physical interaction with hydrophobic drugs. Griseofulvin was used as a model drug in this study. The loading efficiency and release profile of the drug were measured by HPLC. The loading efficiency was about 54%. The release behavior was sustained for a prolonged time of 12 days. The proposed lipid-polymer system with biodegradable and biocompatible properties has promising potential as a passive-targeting drug delivery carrier because of its small particle size.

• Macromolecular Research
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• v.16 no.8
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• pp.682-685
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• 2008

The aim of this work was to develop and evaluate solid lipid nanoparticles (SLN) containing all-trans-retinoic acid (ATRA) for topical delivery. SLN composed of coconut oil and curdlan improved the suspension instability of ATRA in aqueous solution. The photodegradation of ATRA by light was reduced by incorporation in SLN. The loading efficiency of ATRA in SLN was higher than 95% (w/w). The amounts of ATRA released from SLN at $4^{\circ}C$ and at $37^{\circ}C$ were less than 15% and more than 60% (w/w) for 96 h, respectively. The ATRA-loaded SLN can be used as a potential carrier for topical delivery.

• Journal of Pharmaceutical Investigation
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• v.38 no.1
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• pp.39-43
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• 2008

Cyclosporin A (CyA), a potent immunosuppressive drug used in allogeneic transplants and autoimmune disease, is a typical water-insoluble drug. Recently, nanoparticle carriers were investigated to improve the intestinal absorption of drugs. In this study, CyA-loaded nanostructured lipid carriers (NLCs) were prepared from a hot o/w emulsion using the high pressure homogenization method. The NLCs were consisted of cationic lipids, solid lipids, liquid lipids (oils), surfactant and stabilizer. Encapsulation efficiency of CyA in NLCs was approximately 71%. The average particle size and zeta potential of NLCs were below 250 nm and above +40 mV, respectively. The morphology of NLCs was confirmed by transmission electron microscopy (TEM) analysis. Compared to the CyA powder, higher in vitro release of CyA from NLCs was observed after burst release within 30 min. Thus, CyA-loaded NLCs could be applied not only for parenteral route but also for gastrointestinal administration, which needs further investigation.

• Mass Spectrometry Letters
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• v.8 no.4
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• pp.105-108
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• 2017

Recently, deciduous teeth have been proposed as a promising biomatrix for estimating internal and external chemical exposures of an individual from prenatal periods to early childhood. Therefore, detection of organic chemicals in teeth has received increasing attention. Organic materials in tooth matrix are mostly collagen type proteins, but lipids and other small organic chemicals are also present in the tooth matrix. In this study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) was employed to obtain lipid fingerprints from deciduous teeth. Phospholipids and triacylglcerols (TAGs) from deciduous teeth were successfully detected by MALDI MS with 2,5-dihydroxybenzoic acid (DHB) or gold nanoparticle (AuNP) as a matrix.