• IMMUNE NETWORK
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• v.13 no.3
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• pp.81-85
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• 2013

The mucosal surfaces are constantly exposed to incoming pathogens which can cause infections that result in severe morbidity and/or mortality. Studies have reported that mucosal immunity is important for providing protection against these pathogens and that mucosal vaccination is effective in preventing local infections. For many years, the sublingual mucosa has been targeted to deliver immunotherapy to treat allergic hypersensitivities. However, the potential of vaccine delivery via sublingual mucosal has received little attention until recently. Recent studies exploring such potential have documented the safety and effectiveness of sublingual immunization, demonstrating the ability of sublingual immunization to induce both systemic and mucosal immune responses against a variety of antigens, including soluble proteins, inter particulate antigens, and live-attenuated viruses. This review will summarize the recent findings that address the promising potential of sublingual immunization in proving protection against various mucosal pathogens.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.63-73
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• 2010

Solid lipid nanoparticles (SLNs) have emerged to combine the advantages of polymeric nanoparticles and lipid emulsions in early 1990s. SLNs can present several desirable properties derived from the solid state core. When formulating SLNs, there should be careful considerations about the physical state of the inner solid lipid core and its polymorphism and supercooling behavior. In this review, SLNs were compared to lipid emulsion and emulsion of supercooled melt to understand the unusual behaviors compared to lipid emulsions and to have insights into stability and release mechanism. SLNs have been regarded as biocompatible system because lipids are usually well-tolerable ingredients than polymers. Several studies showed good tolerability of SLNs in terms of cytotoxicity and hemolysis. Similar to various other nanoparticulate drug delivery systems, SLNs can also change biodistribution of the incorporated drugs in a way to enhance therapeutic effect. Most of all, large scale production of SLNs was extablished wihtout using organic solvents. Although there is no SLN product in the market till date, several advantagious properties of SLNs and the progress we have seen so far would make commercial product of SLNs possible before long and encourage research community to apply SLN-based formulations for water-insoluble drugs.

• Biomedical Science Letters
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• v.12 no.3
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• pp.177-183
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• 2006

To demonstrate the effect of formulation conditions and evaluations of structural integrity from ovalbumin containing poly lactide glycolide copolymer (PLGA) microspheres for Vaccine delivery, OVA microspheres were prepared by a W/O/W multiple emulsion solvent extraction technique. Dichloromethan (DCM) and Ethyl acetate (EA) were applied as an organic phase and poly vinyl alcohol (PVA) as a secondary emulsion stabilizer. Microspheres were characterized for particle size, morphology (optical microscopy and Scanning Electron Microscope (SEM)). Protein denaturation was evaluated by size exclusion chromatography (SEC), SDS-PAGE and isoelectric focusing (IEF). Residual organic solvent was estimated by gas chromatography (GC) and differential scanning calorimetry (DSC). Optical photomicrograph and SEM revealed that micro spheres were typically spherical but various morphologies were observed. Mean particle size $(d_{vs})$ of microspheres were in the range of $3{\sim}50{\mu}m$. Also, The protein stability was not affected by the fonnulation process and residual organic solvent was beyond the detection below 0.1ppm. These results demonstrated that micro spheres might be a good candidate for the parenteral vaccine delivery system.

• CELLMED
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• v.11 no.1
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• pp.6.1-6.7
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• 2021

In situ gelling devices, as they enter the body, are dosage forms in the shape of the sol but turn into gel types under physiological circumstances. Transition from sol to gel is contingent on one or a mixture of diverse stimuli, such as transition of pH control of temperature, irradiation by UV, by the occurrence of certain ions or molecules. Such characteristic features may be commonly employed in drug delivery systems for the production of bioactive molecules for continuous delivery vehicles. The technique of in situ gelling has been shown to be impactful in enhancing the potency of local or systemic drugs supplied by non-parenteral pathways, increasing their period of residence at the absorption site. Formulation efficacy is further improved with the use of mucoadhesive agents or the use of polymers with both in situ gelling properties and the ability to bind with the mucosa/mucus. The most popular and common approach in recent years has provided by the use of polymers with different in situ gelation mechanisms for synergistic action between polymers in the same formulation. In situ gelling medicine systems in recent decades have received considerable interest. Until administration, it is in a sol-zone and is able to form gels in response to various endogenous factors, for e.g elevated temperature, pH changes and ions. Such systems can be used in various ways for local or systemic supply of drugs and successfully also as vehicles for drug-induced nano- and micro-particles. In this review we will discuss about various aspects about use of these in situ gels as novel drug delivery systems.

• Journal of Plant Biotechnology
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• v.37 no.3
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• pp.250-261
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• 2010

The expression of vaccine antigens in transgenic plants has the potential to provide a convenient, stable, safe approach for oral vaccination alternative to traditional parenteral vaccines. Over the past two decades, many different vaccine antigens expressed via the plant nuclear genome have elicited appropriate immunoglobulin responses and have conferred protection upon oral delivery. Up to date, efforts to produce antigen proteins in plants have focused on potato, tobacco, tomato, banana, and seed (maize, rice, soybean, etc). The choice of promoters affects transgene transcription, resulting in changes not only in concentration, but also in the stage tissue and cell specificity of its expression. Inclusion of mucosal adjuvants during immunization with the vaccine antigen has been an important step towards the success of plant-derived vaccines. In animal and Phase I clinical trials several plant-derived vaccine antigens have been found to be safe and induce sufficiently high immune response. Future areas of research should further characterize the induction of the mucosal immune response and appropriate dosage for delivery system of animal and human vaccines. This article reviews the current status of development in the area of the use of plant for the development of oral vaccines.

• Journal of Pharmaceutical Investigation
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• v.27 no.1
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• pp.15-22
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• 1997

The mucosal route of administration(nasal, buccal, conjunctival and vaginal) has recently been considered as an alternative to parenteral delivery for many peptide drugs because enzymatic degradation of these agents may be partly avoided. The objective of these study was to establish the optimal mucosal administration dosage form of $LHRH/[D-Ala^6]LHRH$, based on presystemic metabolism. We reported previously the peptidase inhibition effect of medium chain fatty acid salts(sodium caprylate, soadium caprate and sodium laurate), EDTA and STDHF on the proteolysis of $LHRH/[D-Ala^6]LHRH$ in rabbit mucosal homgenates. We also reported that EDTA, STDHF and sodium laurate markedly increased the potency of $LHRH/[D-Ala^6]LHRH$ solution applied vaginally. In the present study, by administration of polycarbophil hydrogel containing LHRH the ovulation inducing activity was 3.3 times greater than solution. These results indicate not only peptidase inhibitor but also polycarbophil hydrogel significantly improved the absorption of this drug. The results of this study would provide the feasibility as a rational dosage form for improving bioavailability and self administration of this hydrogel by the vaginal application.

• Biomedical Science Letters
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• v.12 no.4
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• pp.443-450
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• 2006

To demonstrate their possibilities as an enhanced vaccine delivery system, protein-loaded Poly lactide glycolide copolymer (PLGA) microspheres were prepared with different physical characteristics. Ethyl acetate (EA) solvent extraction process was employed to prepare microspheres and the effects of process parameters on drug release properties were evaluated. The biodeuadability of microspheres was also evaluated by the pH change and GPC (Gel permeation chromatography). Primary IgG antibody responses in BALB/c mice were compared with protein saline solutions as negative controls and adsorbed alum suspensions as positive controls after single subcutaneous injection for in vivo studies. The microspheres showed a erosion with a highly porous structure and did not keep their spherical shape at 45 days and this result could be confirmed by GPC. In vitro release of proteinous drug showed initial burst effect in all batches of microspheres, followed by gradual release over the next 4 weeks. PLGA microspheres were degraded until 45 days and the secondary structure of OVA was not affected by the preparation method. Enzyme-linked immunosorbent assays demonstrated that the single subcutaneous administrations of OVA-loaded PLGA microspheres induced enhanced serum IgG antibody response in comparison to negative and positive controls. These results demonstrated that microspheres providing the controlled release of antigens might be useful in advanced vaccine formulations for the parenteral carrier system.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.225.1-225.1
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• 2003

Purpose. Paclitaxel has demonstrated significant activity in clinical trials against a wide variety of tumors. The clinical application of Taxol$\^$\ulcorner/, a commercial product of solubilized paclitaxel with co solvents of ethanol and Cremophor, however, has been limited largely by hypersensitivity of the excipient. The aim of this study was to formulate paclitaxel-loaded lipid nanodispersions (Px-LN) for i.v. administration without toxic excipients, and to evaluate in vitro characteristics and in vivo pharmacokinetic behaviors. (omitted)

• Nutrition Research and Practice
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• v.5 no.5
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• pp.450-454
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• 2011

The beneficial effects of total parenteral nutrition (TPN) in improving the nutritional status of malnourished patients during hospital stays have been well established. However, recent randomized trials and meta-analyses have reported an increased rate of TPN-associated complications and mortality in critically ill patients. The increased risk of complications during TPN therapy has been linked to the development of hyperglycemia, especially during the first few days of TPN therapy. This retrospective study was conducted to determine whether the amount of dextrose from TPN in the 1st week in the intensive care unit (ICU) was related to the development of hyperglycemia and the clinical outcome. We included 88 non-diabetic critically ill patients who stayed in the medical ICU for more than two days. The subjects were 65 ${\pm}$ 16 years old, and the mean APACHE (Acute Physiology and Chronic Health Evaluation) II score upon admission was 20.9${\pm}$7.1. The subjects received 2.3${\pm}$1.4 g/kg/day of dextrose intravenously. We divided the subjects into two groups according to the mean blood glucose (BG) level during the 1st week of ICU stay: <140 mg/dl vs ${\geq}$ 140 mg/dl. Baseline BG and the amount of dextrose delivered via TPN were significantly higher in the hyperglycemia group than those in the normoglycemia group. Mortality was higher in the hyperglycemia group than in the normoglycemia group (42.4% vs 12.8%, P=0.008). The amount of dextrose from TPN was the only significant variable in the multiple linear regression analysis, which included age, APACHE II score, baseline blood glucose concentration and dextrose delivery via TPN as independent variables. We concluded that the amount of dextrose delivered via TPN might be associated with the development of hyperglycemia in critically ill patients without a history of diabetes mellitus. The amount of dextrose in TPN should be decided and adapted carefully to maintain blood glucose within the target range.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.157-162
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• 2013

Application of vaccine materials through oral mucosal route confers great economical advantage in animal farming industry due to much less vaccination cost compared with that of injection-based vaccination. In particular, oral administration of recombinant protein antigen against foot-and- mouth disease virus (FMDV) is an ideal strategy because it is safe from FMDV transmission during vaccine production and can induce antigen-specific immune response in mucosal compartments, where FMDV infection has been initiated, which is hardly achievable through parenteral immunization. Given that effective delivery of vaccine materials into immune inductive sites is prerequisite for effective oral mucosal vaccination, M cell-targeting strategy is crucial in successful vaccination since M cells are main gateway for luminal antigen influx into mucosal lymphoid tissue. Here, we applied previously identified M cell-targeting ligand Co1 to VP1 of FMDV in order to test the possible oral mucosal vaccination against FMDV infection. M cell-targeting ligand Co1-conjugated VP1 interacted efficiently with M cells of Peyer's patch. In addition, oral administration of ligand-conjugated VP1 enhanced the induction of VP1-specific IgG and IgA responses in systemic and mucosal compartments, respectively, in comparison with those from oral administration of VP1 alone. In addition, the enhanced VP1-specific immune response was found to be due to antigen-specific Th2-type cytokine production. Collectively, it is suggested that the M cell-targeting strategy could be applied to develop efficient oral mucosal vaccine against FMDV infection.