Development of cell-penetrating peptide-modified MPEG-PCL diblock copolymeric nanoparticles for systemic gene delivery

Tanaka, Ko; Kanazawa, Takanori; Shibata, Yasunori; Suda, Yumiko; Fukuda, Tsunehiko; Takashima, Yuuki; Okada, Hiroaki

doi:10.1016/j.ijpharm.2010.06.028

Cited by 64 publications

(46 citation statements)

References 23 publications

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“…In addition, it was clearly observed that no drug crystals surrounded the NPs, suggesting that the preparation process was free from drug crystallization. The MPEG-PCL spectrum was also in line with previous reports [7,24] , further implying that MPEG-PCL was successfully synthesized. There was little or no interaction between the drug and carrier demon- …”

Section: Discussionsupporting

confidence: 89%

“…Grafting PCL to other watersoluble polymers has been widely reported to enhance its biodegradation rate. Methoxy poly(ethylene glycol) (MPEG)-based modification has attracted increasing attention in the field of drug delivery due to its relatively low melting point that enables it to be fabricated by existing melt processing techniques and the ability to stabilize the delivery vehicle against undesirable aggregation and non-specific electrostatic www.nature.com/aps Peng W et al Acta Pharmacologica Sinica npg interactions with its surroundings [7] . Furthermore, PEG segments also counteract protein absorption, which increase the circulatory half-life in the body [8][9][10] due to its chain flexibility, high surface density and the absence of functional groups.…”

Section: Introductionmentioning

confidence: 99%

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Oral delivery of capsaicin using MPEG-PCL nanoparticles

et al. 2014

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Aim: To prepare a biodegradable polymeric carrier for oral delivery of a water-insoluble drug capsaicin (CAP) and evaluate its quality. Methods: CAP-loaded methoxy poly (ethylene glycol)-poly(ε-caprolactone) nanoparticles (CAP/NPs) were prepared using a modified emulsification solvent diffusion technique. The quality of CAP/NPs were evaluated using transmission electron microscopy, powder X-ray diffraction, differential scanning calorimetry and Fourier transform infrared techniques. A dialysis method was used to analyze the in vitro release profile of CAP from the CAP/NPs. Adult male rats were orally administered CAP/NPs (35 mg/kg), and the plasma concentrations of CAP were measured with a validated HPLC method. The morphology of rat gastric mucosa was studied with HE staining. Results: CAP/NPs had an average diameter of 82.54±0.51 nm, high drug-loading capacity of 14.0%±0.13% and high stability. CAP/NPs showed a biphasic release profile in vitro: the burst release was less than 25% of the loaded drug within 12 h followed by a more sustained release for 60 h. The pharmacokinetics study showed that the mean maximum plasma concentration was observed 4 h after oral administered of CAP/NPs, and approximately 90 ng/mL of CAP was detected in serum after 36 h. The area under the curve for the CAP/NPs group was approximately 6-fold higher than that for raw CAP suspension. Histological studies showed that CAP/NPs markedly reduced CAP-caused gastric mucosa irritation. Conclusion: CAP/NPs significantly enhance the bioavailability of CAP and markedly reduce gastric mucosa irritation in rats.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Oral delivery of capsaicin using MPEG-PCL nanoparticles

et al. 2014

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“…28,29) Both analogs were used after purification by reverse-phase HPLC. The molecular weight of each analog was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS): Tat analog, 1627; AT1002 analog, 939.…”

Section: Methodsmentioning

confidence: 99%

Development of an Efficient Transdermal Delivery System of Small Interfering RNA Using Functional Peptides, Tat and AT-1002

Uchida

Kanazawa

Takashima

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The Tat analog, which consists of Cys-Gly-NH2 added to the N terminus of HIV-Tat (48 -57), and the AT1002 analog, which consists of Gly and Cys-Gly-NH2 added to the C and N termini of AT1002 (Table 2), were synthesized as PTD or permeability peptides using the 9-fluorenylmethyloxycarbonyl solid-phase peptide synthesis method with an ABI 433A peptide synthesizer (Applied Biosystems, Tokyo, Japan) as reported previously (Tanaka et al, 2010;Uchida et al, 2011). Both analogs were used after purification by reverse-phase high-performance liquid chromatography.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effects on Atopic Dermatitis by Anti-RelA Short Interfering RNA Combined with Functional Peptides Tat and AT1002

Uchida

Kanazawa²,

Kawai³

et al. 2011

J Pharmacol Exp Ther

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Atopic dermatitis (AD) has high morbidity and poor prognosis because safe and effective treatments are scarce. Recently, short interfering RNA (siRNA) has shown promise as an effective treatment for targeting specific aberrantly expressed genes. However, naked siRNAs are too inefficient because of various enzymatic, membrane, and cellular barriers. We previously reported that a Tat analog acting as a cell-penetrating peptide, combined with AT1002, which reversibly increases paracellular transport of molecules across the epidermal barrier in epidermis-disrupted mice and enhances the skin permeation of water-soluble siRNA. In the present study, to develop a novel treatment for AD, we determined the intradermal permeation of siRNAs and the antiallergic effects of a siRNA that silences RelA, a member of the nuclear factor-B family, using Tat and AT1002 peptides in an AD mouse model. We first showed that the Tat analog and AT1002 delivered siRNA into the skin of ICR mice and, upon topical application to the AD-induced ears of NC/Nga mice, changed zonula occludens protein 1 expression. In addition, the silencing effects on the mRNA of RelA in JAWS II cells transfected with siRNA oligonucleotides for mouse RelA, complexed with Tat, were as effective as a commercial vector. Furthermore, the ear thickness, clinical skin severity, topical cytokine levels, and serum IgE production in AD model mice treated with anti-RelA siRNA with Tat and AT1002 were improved.

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Development of cell-penetrating peptide-modified MPEG-PCL diblock copolymeric nanoparticles for systemic gene delivery

Cited by 64 publications

References 23 publications

Oral delivery of capsaicin using MPEG-PCL nanoparticles

Oral delivery of capsaicin using MPEG-PCL nanoparticles

Development of an Efficient Transdermal Delivery System of Small Interfering RNA Using Functional Peptides, Tat and AT-1002

Therapeutic Effects on Atopic Dermatitis by Anti-RelA Short Interfering RNA Combined with Functional Peptides Tat and AT1002

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