Pretreatment with Epidermal Growth Factor Enhances Naked Plasmid DNA Transfer onto Gastric Serosal Surface in Mice

Miyamoto, Hirotaka; Baba, Sumie; Nakajima, Sayuri; Mine, Toyoharu; Yoshikawa, Naoki; Fumoto, Shintaro; Nishida, Koyo

doi:10.1248/bpb.35.903

Cited by 2 publications

(1 citation statement)

References 45 publications

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“…As for the organ surface instillation method, we succeeded in enhancing the transfection efficiency of naked plasmid DNA by several strategies. Pretreatment with epidermal growth factor (EGF) enhanced transgene expression and increased transgene-positive cells on the stomach after instillation of naked plasmid DNA onto it [162]. Rubbing the gastric serosal surface with a medical spoon after instillation of naked plasmid DNA onto the stomach was more effective than EGF pretreatment [163].…”

Section: Improving Methods For Targeted Gene Deliverymentioning

confidence: 99%

Targeted Gene Delivery: Importance of Administration Routes

Fumoto¹,

Kawakami²,

Hashida³

et al. 2013

Novel Gene Therapy Approaches

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Section: Improving Methods For Targeted Gene Deliverymentioning

confidence: 99%

Targeted Gene Delivery: Importance of Administration Routes

Fumoto¹,

Kawakami²,

Hashida³

et al. 2013

Novel Gene Therapy Approaches

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Organ surface application method-new DDS for digestive diseases

Nishida

Fumoto

2018

Official Journal of the Japan Society of Drug Delivery System

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For therapy of digestive diseases, generally drug treatment has been employed. There have been problems due to even drug distribution in the target and non-target organ. Since it is difficult to attain local drug activity after conventional administration such as intravenous and oral routes, we have tried to develop a new administration system utilizing drug absorption from the organ surface such as liver in the peritoneal cavity. As a non-invasive procedure, endoscopic surgery would enable us to achieve drug targeting to the diseased region in the peritoneal cavity. Although direct drug application to the organ surface could yield local drug availability, drug absorption characteristics from the organ surface such as liver surface had not been reported in the literature.Therefore, we first analyzed the efficiency of absorption of several organic anions and dextrans of various molecular weights, as marker compounds, following application to the rat liver surface in vivo employing a cylindrical diffusion cell. Each compound was absorbed from the rat liver surface with the different rates depending on the physicochemical properties. The absorption process from the liver surface might not obey an active transport system because of no detectable effect by dose and transport inhibitors. In addition, molecular weight and lipophilicity were found to be one of determinant factors of absorption through the liver surface. The ability of targeting to the desired region in the liver was enhanced significantly by application to the liver surface, compared to intravenous administration. Viscous additives, absorption enhancer, and vasomodulaters were proved to be effective to improve the drug availability in the target region. We also have obtained several expecting results from the application of this new drug delivery system for anticancer drugs. On the other hand, I have clarified the characteristics of drug absorption from the surfaces of the kidney, stomach, cecum and small intestine, and expect to apply the physiological findings to other fields. Furthermore, it is possible to apply the organ surface administration to genetic medicine. We successfully enhanced transgene expression onto the organ surface based on various strategies. 消化器疾患の治療では、全身および非病巣への薬物分布による重篤な副作用が大きな障壁となっている。この問題を解決するための、消化器疾患に対する新たな DDS 手段として、腹腔内の臓器表面から薬物を浸透させる臓器表面投与法を考案した。円筒状の拡散セルにより吸収部位が肝臓表面に限定された実験系を新たに構築して、腹腔内の消化器の代表例として肝臓表面からの薬物吸収性を検討した。物性の異なる各種マーカー化合物は、分子量や脂溶性などの物理化学的性質に基づいて、肝臓表面より良好に吸収される可能性を初めて証明した。さらに、抗がん薬に対する本投与形態の適用に関して、肝臓内の投与部位近傍における5 -FU の高度な分布を認めた。他の腹腔内臓器である腎臓や消化管漿膜表面からの薬物吸収性や臓器分布についても検討を加えている。また、臓器表面投与法は遺伝子医薬品にも応用可能で、さまざまな戦略により遺伝子発現を促進できることも明らかにした。

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Pretreatment with Epidermal Growth Factor Enhances Naked Plasmid DNA Transfer onto Gastric Serosal Surface in Mice

Cited by 2 publications

References 45 publications

Targeted Gene Delivery: Importance of Administration Routes

Targeted Gene Delivery: Importance of Administration Routes

Organ surface application method-new DDS for digestive diseases

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