Cell entry of cell penetrating peptides: tales of tails wagging dogs

Jones, Arwyn Tomos; Sayers, Edward J.

doi:10.1016/j.jconrel.2012.04.003

Cited by 215 publications

(200 citation statements)

References 134 publications

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“…Incorporation into the delivery system of new methods to increase the membrane (27,28). CPPs comprise short polycationic peptides based on hydrophobic sequences derived from signal peptides, viral peptides, or other sources (29), and are recognized as promising tools for the intracellular delivery of macromolecular medicines (30)(31)(32)(33). Our recent study has shown that the absorption of insulin and other medicinal peptides and proteins across the epithelial mucosal membrane can be improved significantly by the coadministration of new CPPs with biodrug cargos (13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across the Rat Small Intestinal Membrane

Khafagy

Iwamae

Kamei

et al. 2015

AAPS J

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Abstract. We have reported that the cell-penetrating peptide (CPP) penetratin acts as a potential absorption enhancer in oral insulin delivery systems and that this action occurs through noncovalent intermolecular interactions. However, the region-dependent role of CPPs in intestinal insulin absorption has not been clarified. To identify the intestinal region where CPPs have the most effect in increasing insulin absorption, the region-dependent action of penetratin was investigated using in situ closed intestinal loops in rats. The order of the insulin area under the insulin concentration-time curve (AUC) increase effect by L-penetratin was ileum>jejunum>duodenum>colon. By contrast, the AUC order after coadministration of insulin with D-penetratin was colon>duodenum≥jejunum and ileum. We also compared the effects of the L-and D-forms of penetratin, R8, and PenetraMax on ileal insulin absorption. Along with the CPPs used in this study, L-and D-PenetraMax produced the largest insulin AUCs. An absorption study using ilea pretreated with CPPs showed that PenetraMax had no irreversible effect on the intestinal epithelial membrane. The degradation of insulin in the presence of CPPs was assessed in rat intestinal enzymatic fluid. The half-life (t 1/2 ) of insulin increased from 14.5 to 23.7 and 184.7 min in the presence of L-and D-PenetraMax, respectively. These enzymatic degradation-resistant effects might contribute partly to the increased ileal absorption of insulin induced by D-PenetraMax. In conclusion, this study demonstrated that the ability of the L-and D-forms of penetratin to increase intestinal insulin absorption was maximal in the ileum and the colon, respectively, and that D-PenetraMax is a powerful but transient enhancer of oral insulin absorption.

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Section: Discussionmentioning

confidence: 99%

Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across the Rat Small Intestinal Membrane

Khafagy

Iwamae

Kamei

et al. 2015

AAPS J

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“…These include HIVderived HGP-peptide (Kwon et al 2010), TATfusion peptide (Wadia et al 2004), influenza virus hemagglutinin HA-2 amino-terminal fusogenic peptide (Wagner et al 1992), and papillomavirus L240 peptide (Kwon et al 2008). These natural cell-penetrating peptides have also inspired several synthetic strategies, and several artificial peptides have been proposed to favor cellular delivery (Subbarao et al 1987;Wyman et al 1997;Stayton et al 2000;Jones and Sayers 2012). There is still much unknown about the cell penetration and poration mechanisms of these peptides as well as concerns regarding immunogenicity and cytotoxicity (Jones and Sayers 2012).…”

Section: Endosome Escape Strategiesmentioning

confidence: 99%

“…These natural cell-penetrating peptides have also inspired several synthetic strategies, and several artificial peptides have been proposed to favor cellular delivery (Subbarao et al 1987;Wyman et al 1997;Stayton et al 2000;Jones and Sayers 2012). There is still much unknown about the cell penetration and poration mechanisms of these peptides as well as concerns regarding immunogenicity and cytotoxicity (Jones and Sayers 2012). One way around the intrinsic immunogenicity of pathogen-derived peptides is to design synthetic polymers and lipids that enhance endosomal escape.…”

Section: Endosome Escape Strategiesmentioning

confidence: 99%

Exploiting Endocytosis for Nanomedicines

Akinc

Battaglia

2013

Cold Spring Harbor Perspectives in Biology

190

169

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In this article, we briefly review the endocytic pathways used by cells, pointing out their defining characteristics and highlighting physical limitations that may direct the internalization of nanoparticles to a subset of these pathways. A more detailed description of these pathways is presented in the literature. We then focus on the endocytosis of nanomedicines and present how various nanomaterial parameters impact these endocytic processes. This topic is an area of active research, motivated by the recognition that an improved understanding of how nanomaterials interact at the molecular, cellular, and whole-organism level will lead to the design of better nanomedicines in the future. Next, we briefly review some of the important nanomedicines already on the market or in clinical development that serve to exemplify how endocytosis can be exploited for medical benefit. Finally, we present some key unanswered questions and remaining challenges to be addressed by the field.

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“…Potential intracellular drug delivery carriers, such as Tat-derived peptides (93), have also been studied. FRAP was used to investigate the intracellular mobility of Tat-peptides with cargoes of different molecular weights below and above the threshold for diffusion through the nuclear pores (94).…”

Section: Drug Delivery Inside Cellsmentioning

confidence: 99%

FRAP in Pharmaceutical Research: Practical Guidelines and Applications in Drug Delivery

et al. 2013

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Fluorescence recovery after photobleaching (FRAP) is a fluorescence microscopy technique that has attracted a lot of interest in pharmaceutical research during the last decades. The main purpose of FRAP is to measure diffusion on a micrometer scale in a non-invasive and highly specific way, making it capable of measurements in complicated biomaterials, even in vivo. This has proven to be very useful in the investigation of drug diffusion inside different tissues of the body and in materials for controlled drug delivery. FRAP has even found applications for the improvement of several medical therapies and for the field of diagnostics. In this review, an overview is given of the different applications of FRAP in pharmaceutical research, together with essential guidelines on how to perform and analyse FRAP experiments.

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Cell entry of cell penetrating peptides: tales of tails wagging dogs

Cited by 215 publications

References 134 publications

Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across the Rat Small Intestinal Membrane

Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across the Rat Small Intestinal Membrane

Exploiting Endocytosis for Nanomedicines

FRAP in Pharmaceutical Research: Practical Guidelines and Applications in Drug Delivery

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