• Title/Summary/Keyword: systemic delivery

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Protective Immunity Induced by Systemic and Mucosal Delivery of DNA Vaccine Expressing Glycoprotein B of Pseudorabies Virus

  • Yoon, Hyun-A;Han, Young-Woo;Aleyas, Abi George;George, June Abi;Kim, Seon-Ju;Kim, Hye-Kyung;Song, Hee-Jong;Cho, Jeong-Gon;Eo, Seong-Kug
    • Journal of Microbiology and Biotechnology
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    • v.18 no.3
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    • pp.591-599
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    • 2008
  • A murine model immunized by systemic and mucosal delivery of plasmid DNA vaccine expressing glycoprotein B (pCIgB) of pseudorabies virus (PrV) was used to evaluate both the nature of the induced immunity and protection against a virulent virus. With regard to systemic delivery, the intramuscular (i.m.) immunization with pCIgB induced strong PrV-specific IgG responses in serum but was inefficient in generating a mucosal IgA response. Mucosal delivery through intranasal (i.n.) immunization of pCIgB induced both systemic and mucosal immunity at the distal mucosal site. However, the levels of systemic immunity induced by i.n. immunization were less than those induced by i.m. immunization. Moreover, i.n. genetic transfer of pCIgB appeared to induce Th2-biased immunity compared with systemic delivery, as judged by the ratio of PrV-specific IgG isotypes and Th1- and Th2-type cytokines produced by stimulated T cells. Moreover, the immunity induced by i.n. immunization did not provide effective protection against i.n. challenge of a virulent PrV strain, whereas i.m. immunization produced resistance to viral infection. Therefore, although i.n. immunization was a useful route for inducing mucosal immunity at the virus entry site, i.n. immunization did not provide effective protection against the lethal infection of PrV.

Anti-Hyperalgesic Effects of Meloxicam Hydrogel via Phonophoresis in Acute Inflammation in Rats; Comparing Systemic and Topical Application

  • Kim, Tae-Youl;Kim, Young-Il;Seo, Sam-Ki;Kim, Soo-Hyeun;Yang, Kyu-Ho;Shin, Sang-Chul
    • Biomolecules & Therapeutics
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    • v.17 no.3
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    • pp.305-310
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    • 2009
  • The aim of this study was to determine if a meloxicam hydrogel could be administered in vivo via phonophoretic transdermal delivery using pulsed ultrasound by examining its anti-hyperalgesic effects in a rat carrageenan inflammation model. Carrageenan (1%) was injected into the plantar surface of the right hindpaw, and meloxicam hydrogel was administered via phonophoretic transdermal delivery. Changes in the mechanical and thermal hyperalgesia, as well as swelling, showed that phonophoretic delivery of meloxicam exhibited significantly better anti-hyperalgesic and anti-inflammatory effects than pulsed ultrasound. Topical and systemic application of meloxicam hydrogel using phonophoresis showed similar anti-hyperalgesic effects. These findings suggest that the transdermal administration of a meloxicam hydrogel using phonophoresis by pulsed ultrasound might be useful for treating acute inflammation.

Enhanced mucosal and systemic immune responses by mucosally administered hepatitis B surface antigen: effects of vaccine delivery vehicles and adjuvants

  • Park, Jeong-Sook;Kim, Chong-Kook
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.121-121
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    • 2003
  • The purpose of this study is to investigate the effect of mucosal vaccine delivery vehicles and adjuvants on the local and systemic antibody responses following mucosal immunization of mice with hepatitis B surface antigen (HBsAg). Mice were immunized on days 0 and 21 by administration of hepatitis B surface antigen B (HBsAg) into the vagina. HBsAg was delivered in saline or poloxamer(Pol)-based vehicle containing mucoadhesive polycarbophil (PC). (omitted)

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Recent Advances in Intranasal Drug Delivery (경비 약물전달체계의 최근의 진보)

  • Park, Gee-Bae;Lee, Yong-Suk;Lee, Kwang-Pyo
    • Journal of Pharmaceutical Investigation
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    • v.22 no.2
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    • pp.77-96
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    • 1992
  • In recent years intranasal administration of drugs has received great attention as a convenient and efficent method of drug delivery because of its potential to improve the systemic effect of substances with a poor oral bioavailability. In addition to offering advantages such as rapid absorption, fast onset of action and avoiding the first -pass effect, it provides for delivery of drugs from very lipophilic drugs such as steroids to polar and hydrophilic drugs such as peptides and proteins. However, little is still known about the nature of various barriers existing in the nasal mucosae as well as mechanism by which these molecules are absorbed. This review article therefore intends to discuss nasal physiology, experimental methods and evaluation of absorption from the nasal cavity, factors influencing nasal absorption, mechanism of nasal absorption, approaches to improve the residence time and to obtain the sustained-release effect of intranasally administered drugs, promoters and mechanism for the enhancement of nasal absorption, Several examples for intranasal delivery of various systemically effective drugs will be reviewed and illustrated. Drug metabolism in the nasal mucosae and problems associated with intranasal administration of drugs will be also discussed.

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Research progress on hydrogel-based drug therapy in melanoma immunotherapy

  • Wei He;Yanqin Zhang;Yi Qu;Mengmeng Liu;Guodong Li;Luxiang Pan;Xinyao Xu;Gege Shi;Qiang Hao;Fen Liu;Yuan Gao
    • BMB Reports
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    • v.57 no.2
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    • pp.71-78
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    • 2024
  • Melanoma is one of the most aggressive skin tumors, and conventional treatment modalities are not effective in treating advanced melanoma. Although immunotherapy is an effective treatment for melanoma, it has disadvantages, such as a poor response rate and serious systemic immune-related toxic side effects. The main solution to this problem is the use of biological materials such as hydrogels to reduce these side effects and amplify the immune killing effect against tumor cells. Hydrogels have great advantages as local slow-release drug carriers, including the ability to deliver antitumor drugs directly to the tumor site, enhance the local drug concentration in tumor tissue, reduce systemic drug distribution and exhibit good degradability. Despite these advantages, there has been limited research on the application of hydrogels in melanoma treatment. Therefore, this article provides a comprehensive review of the potential application of hydrogels in melanoma immunotherapy. Hydrogels can serve as carriers for sustained drug delivery, enabling the targeted and localized delivery of drugs with minimal systemic side effects. This approach has the potential to improve the efficacy of immunotherapy for melanoma. Thus, the use of hydrogels as drug delivery vehicles for melanoma immunotherapy has great potential and warrants further exploration.

Smart Polymeric Micelles as Nanocarriers for Gene and Drug Delivery

  • Kataoka, Kazunori
    • Proceedings of the Polymer Society of Korea Conference
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    • 2006.10a
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    • pp.54-55
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    • 2006
  • Polymeric micelles, supramolecular assemblies of block copolymers, are useful nanocarriers for the systemic delivery of drugs and genes. Recently, novel polymeric micelles with various functions such as the targetability and stimuli-sensitivity have been emerged as promising carriers that enhance the efficacy of drugs and genes with minimal side effects. This presentation focuses our recent approach to the preparation of functional block copolymers that are useful for constructing smart micellar delivery systems in advanced therapeutics, including chemo-gene therapy. Particular emphasis is placed on the characteristic behaviors of intracellular environment-sensitive micelles that selectively exert drug activity and gene expression in live cells.

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Application of in situ gelling mucoadhesive delivery system for plasmid DNA as a macromolecule

  • Park, Jeong-Sook;Oh, Yu-Kyoung;Kim, Chong-Kook
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.236.1-236.1
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    • 2002
  • Mucosal administration of drug or therapeutic gene is emerging as a new route of delivery for systemic and local therapeutics. Previously. in situ gelling system has been applied to chemical drug such as acetaminophen. insulin. prostaglandin E1. and clotrimazole. Plasmid DNA has not been delivered in form of in situ gelling vehicles. To improve the intranasal absorption of plasmid DNA. we designed delivery systems composed of provide of in 냐셔 gelling and mucoadhesive polymers. (omitted)

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Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

  • Kang, Eun-Ah;Yun, Chae-Ok
    • BMB Reports
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    • v.43 no.12
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    • pp.781-788
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    • 2010
  • An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene therapy is its limited capacity for effective systemic delivery. Although primary tumors can be treated effectively with intralesional injection of conventional Ad vectors, systemic metastasis is difficult to cure. Systemic administration of conventional naked Ads leads to acute accumulation of Ad particles in the liver, induction of neutralizing antibody, short blood circulation half-life, non-specific biodistribution in undesired organs, and low selective accumulation in the target disease site. Versatile strategies involving the modification of viral surfaces with polymers and nanomaterials have been designed for the purpose of maximizing Ad anti-tumor activity and specificity by systemic administration. Integration of viral and non-viral nanomaterials will substantially advance both fields, creating new concepts in gene therapeutics. This review focuses on current advances in the development of smart Ad hybrid nanocomplexes based on various design-based strategies for optimal Ad systemic administration.

Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors

  • Choi, Sun-Hye;Lee, Na-Eun;Cho, Hee-Jung;Lee, Ra Mi;Rhim, Hyewhon;Kim, Hyoung-Chun;Han, Mun;Lee, Eun-Hee;Park, Juyoung;Kim, Jeong Nam;Kim, Byung Joo;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.264-272
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    • 2021
  • Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

An In sight into Novel Drug Delivery System: In Situ Gels

  • Bashir, Rabiah;Maqbool, Mudasir;Ara, Irfat;Zehravi, Mehrukh
    • 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.