31P solid-state NMR based monitoring of permeation of cell penetrating peptides into skin

Desai, Pinaki R.; Cormier, Ashley R.; Shah, Priyanka; Patlolla, Ram R.; Paravastu, Anant K.; Singh, Mandip

doi:10.1016/j.ejpb.2013.05.003

Cited by 14 publications

(2 citation statements)

References 38 publications

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“…A lot of research strategies have been exploited to overcome the skin barrier temporarily in order to deliver therapeutic agents into the skin. Diverse permeation enhancers including cell penetrating peptides (CPP), fatty acids, lipids, polymers and surfactants have been employed to either create channels or aqueous pores within the stratum corneum to enhance permeation (Desai et al, 2014; Marepally et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers

Boakye

Patel

Singh

2015

International Journal of Pharmaceutics

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The objectives of this study were to develop an innovative investigative model using doxorubicin as a fluorophore to evaluate the skin permeation of nanocarriers and the impact of size and surface characteristics on their permeability. Different doxorubicin-loaded liposomes with mean particle size <130nm and different surface chemistry were prepared by ammonium acetate gradient method using DPPC, DOPE, Cholesterol, DSPE-PEG 2000 and 1,1-Di-((Z)-octadec-9-en-1-yl)pyrrolidin-1-ium chloride (CY5)/DOTAP/1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) as the charge modifier. There was minimal release of doxorubicin from the liposomes up to 8 h; indicating that fluorescence observed within the skin layers was due to the intact liposomes. Liposomes with particle sizes >600nm were restricted within the stratum corneum. DOTAP (p<0.01) and CY5 (p<0.05) liposomes demonstrated significant permeation into the skin than DOPA and PEG liposomes. Tape stripping significantly (p<0.01) enhanced the skin permeation of doxorubicin liposomes but TAT-decorated doxorubicin liposomes permeated better (p<0.005). Blockage of the hair follicles resulted in significant reduction in the extent and intensity of fluorescence observed within the skin layers. Overall, doxorubicin liposomes proved to be an ideal fluorophore-based model. The hair follicles were the major route utilized by the liposomes to permeate skin. Surface charge and particle size played vital roles in the extent of permeation.

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Section: Introductionmentioning

confidence: 99%

Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers

Boakye

Patel

Singh

2015

International Journal of Pharmaceutics

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“…15,16 To date, CPPs have been successfully applied to transport "cargo" across cells, 17 the blood-brain barrier, 18,19 and the skin. 20,21 In the current study, we prepared a dendrimer-based gene vector modified by gadolinium (Gd) chelation and CPPs. We then used MRI to administer and monitor gene delivery in the tumor stroma.…”

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Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer

Wang¹,

Li²,

An³

et al. 2015

IJN

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Background Gene therapy is a very promising technology for treatment of pancreatic ductal adenocarcinoma (PDAC). However, its application has been limited by the abundant stromal response in the tumor microenvironment. The aim of this study was to prepare a dendrimer-based gene-free loading vector with high permeability in the tumor stroma and explore an imaging-guided local gene delivery strategy for PDAC to promote the efficiency of targeted gene delivery. Methods The experimental protocol was approved by the animal ethics committee of Zhongshan Hospital, Fudan University. Third-generation dendrigraft poly-L-lysines was selected as the nanocarrier scaffold, which was modified by cell-penetrating peptides and gadolinium (Gd) chelates. DNA plasmids were loaded with these nanocarriers via electrostatic interaction. The cellular uptake and loaded gene expression were examined in MIA PaCa-2 cell lines in vitro. Permeability of the nanoparticles in the tumor stroma and transfected gene distribution in vivo were studied using a magnetic resonance imaging-guided delivery strategy in an orthotopic nude mouse model of PDAC. Results The nanocarriers were synthesized with a dendrigraft poly-L-lysine to polyethylene glycol to DTPA ratio of 1:3.4:8.3 and a mean diameter of 110.9±7.7 nm. The luciferases were strictly expressed in the tumor, and the luminescence intensity in mice treated by Gd-DPT/plasmid luciferase (1.04×10 4 ±9.75×10 2 p/s/cm 2 /sr) was significantly ( P <0.05) higher than in those treated with Gd-DTPA (9.56×10 2 ±6.15×10 p/s/cm 2 /sr) and Gd-DP (5.75×10 3 ± 7.45×10 2 p/s/cm 2 /sr). Permeability of the nanoparticles modified by cell-penetrating peptides was superior to that of the unmodified counterpart, demonstrating the improved capability of nanoparticles for diffusion in tumor stroma on magnetic resonance imaging. Conclusion This study demonstrated that an image-guided gene delivery system with a stroma-permeable gene vector could be a potential clinically translatable gene therapy strategy for PDAC.

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Core‐multishell nanotransporters enhance skin penetration of the cell‐penetrating peptide low molecular weight protamine

Weindl

Fleige

et al. 2014

Polymers for Advanced Techs

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Several peptides may enable innovative, sophisticated therapeutic approaches. Their hydrophilic nature and high molecular weight, however, often limit the applicability to topical and transdermal treatment. Aiming to enhance drug delivery to the skin, we examined the loading of two model peptides—the Cell‐Penetrating Peptides (CPPs) Low Molecular Weight Protamine (LMWP) and penetratin—to Core‐Multishell (CMS) nanotransporters which are well tolerated and known to enhance skin penetration most efficiently. Furthermore, we followed skin penetration of dye‐tagged LMWP in the presence of CMS nanotransporters taking enzymatic peptide cleavage into account. As expected, Isothermal Titration Calorimetry indicated that the large peptides do not interact with CMS nanotransporters. Additionally, size exclusion chromatography and Dynamic Light Scattering confirmed no loading of CPPs to CMS nanoparticles. Due to less LMWP aggregation, concomitant topical application of LMWP and CMS nanotransporters did not enhance the penetration of intact LWMP but enhanced the penetration of peptide fragments in viable layers of human skin ex vivo. Conclusively, our results indicate that CMS nanotransporters impair the skin barrier function leading to increased skin penetration of less voluminous peptides, which may be of future clinical relevance—in particular with those failing to be CPPs. Copyright © 2014 John Wiley & Sons, Ltd.

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31P solid-state NMR based monitoring of permeation of cell penetrating peptides into skin

Cited by 14 publications

References 38 publications

Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers

Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers

Magnetic resonance-guided regional gene delivery strategy using a tumor stroma-permeable nanocarrier for pancreatic cancer

Core‐multishell nanotransporters enhance skin penetration of the cell‐penetrating peptide low molecular weight protamine

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