Protein Transduction Domain-Containing Microemulsions as Cutaneous Delivery Systems for an Anticancer Agent

Pepe, Dominique; Mccall, Melissa; Zheng, Haian; Lopes, Luciana B.

doi:10.1002/jps.23482

Cited by 41 publications

(39 citation statements)

References 70 publications

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“…13 A surfactant mixture was composed of BRIJ:ethanol:propylene glycol at 2:1:1 (w/w/w) and was mixed with monocaprylin (oil phase) at 1.3:1 ratio, followed by addition of the aqueous phase at 43%. This concentration of water has been demonstrated to be sufficient to create an oil-in-water system.…”

Section: Methods Preparation Of Mesmentioning

confidence: 99%

“…This concentration of water has been demonstrated to be sufficient to create an oil-in-water system. 13 The pH of the formulations was kept between 5 and 5.5, because the skin surface pH ranges between 5 and 5.9, and formulations displaying pH closer to this range are generally considered safe. 24 Paclitaxel was incorporated in the oil phase to obtain a final concentration of 0.5% (w/w), whereas penetratin, transportan, or TAT was added to the aqueous phase to obtain a final concentration of 1 mM.…”

Section: Methods Preparation Of Mesmentioning

confidence: 99%

“…13 All PTD-containing formulations were cationic, and thus, differences among the nature of charge (cationic versus anionic) should not interfere with formulation-mediated delivery as suggested by Baspinar and Borchert. 38 …”

Section: Formulation Characterizationmentioning

confidence: 96%

“…Microemulsions (MEs) were selected as nanocarriers due to their simple preparation (since there is no special requirement in terms of energy supply), thermodynamic stability, and versatility of composition, which can reduce costs. 11,12 Considering that drug penetration can be enhanced when cationic lipids, protein transduction domains (PTDs), and pore-forming antimicrobial peptides are included in nanocarriers, [13][14][15][16] we evaluated the effects of adding three different types of PTDs on the microemulsion safety and penetration-enhancing ability.…”

Section: Introductionmentioning

confidence: 99%

“…17,19,20 Penetratin, representative of secondary amphipathic PTDs, was used due to its penetration-enhancing effect demonstrated by our group and others. 13,21 Secondary amphipathic PTDs display their amphipathic properties after interacting with certain lipids and adoption of a helical structure separating charged and uncharged residues. 17 TAT, one of the most studied PTDs, was selected to represent nonamphipathic peptides.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Pepe¹,

Carvalho²,

Mccall³

et al. 2016

IJN

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In this study, the ability of nanocarriers containing protein transduction domains (PTDs) of various classes to improve cutaneous paclitaxel delivery and efficacy in skin tumor models was evaluated. Microemulsions (MEs) were prepared by mixing a surfactant blend (polyoxyethylene 10 oleoyl ether, ethanol and propylene glycol), monocaprylin, and water. The PTD transportan (ME-T), penetratin (ME-P), or TAT (ME-TAT) was added at a concentration of 1 mM to the plain ME. All MEs displayed nanometric size (32.3–40.7 nm) and slight positive zeta potential (+4.1 mV to +6.8 mV). Skin penetration of paclitaxel from the MEs was assessed for 1–12 hours using porcine skin and Franz diffusion cells. Among the PTD-containing formulations, paclitaxel skin (stratum corneum + epidermis and dermis) penetration at 12 hours was maximized with ME-T, whereas ME-TAT provided the lowest penetration (1.6-fold less). This is consistent with the stronger ability of ME-T to increase transepidermal water loss (2.4-fold compared to water) and tissue permeability. The influence of PTD addition on the ME irritation potential was assessed by measuring interleukin-1α expression and viability of bioengineered skin equivalents. A 1.5- to 1.8-fold increase in interleukin-1α expression was induced by ME-T compared to the other formulations, but this effect was less pronounced (5.8-fold) than that mediated by the moderate irritant Triton. Because ME-T maximized paclitaxel cutaneous localization while being safer than Triton, its efficacy was assessed against basal cell carcinoma cells and a bioengineered three-dimensional melanoma model. Paclitaxel-containing ME-T reduced cells and tissue viability by twofold compared to drug solutions, suggesting the potential clinical usefulness of the formulation for the treatment of cutaneous tumors.

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Section: Methods Preparation Of Mesmentioning

confidence: 99%

Section: Methods Preparation Of Mesmentioning

confidence: 99%

Section: Formulation Characterizationmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Pepe¹,

Carvalho²,

Mccall³

et al. 2016

IJN

Self Cite

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Bioengineered Biomimetic and Bioinspired Noninvasive Drug Delivery Systems

Rahamim

Azagury

2021

Adv Funct Materials

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The main purpose herein is to provide an up-to-date review on noninvasive biomimetic, bioinspired, and bioengineered drug delivery system (DDS). Noninvasive DDS is an ever-growing field critical for the applicability of drugs. It offers noninvasive administration routes with improved controlled, targeted, and triggered drug delivery. Noninvasive DDS employ many approaches and strategies, such as, nano-and microparticles, lipid-based systems, sonophoresis, electrophoresis and iontophoresis, penetration enhancers, microneedles, and gels. The last decade seen a surge in research papers employing the paradigms of biomimicry, bioinspiration, and bioengineering. However, since the use of these terms in noninvasive DDS field is often inconsistent and unclear, some generalized perspectives are provided on the possible usage of these terms in future publications. Additionally, a critical discussion on the novelty and origins of these paradigms is provided. The advantages and disadvantages of each of the noninvasive routes and their current main limitations are summarized. The main aspects of indicated fields are discussed: The unique physiology of the related tissues, the main hurdles for mass transport, the various DDS tested, and materials selection. Finally, the basic concepts and therapeutic effects of these DDS are discussed and future venues for noninvasive biomimetic, bioinspired, and bioengineered DDS research are proposed.

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Development of a method for quantitative determination of the cytotoxic agent piplartine (piperlongumine) in multiple skin layers

Carvalho

Giacone

Costa-Lotufo

et al. 2018

Biomedical Chromatography

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This study reports the development of a simple and reproducible method, with high rates of recovery, to extract the cytotoxic agent piplartine from skin layers, and a sensitive and rapid UV-HPLC method for its quantification. Considering the potential of piplartine for topical treatment of skin cancer, this method may find application for formulation development and pharmacokinetics studies to assess cutaneous bioavailability. Porcine skin was employed as a model for human tissue. Piplartine was extracted from the stratum corneum (SC) and remaining viable skin layers (VS) using methanol, vortex homogenization and bath sonication, and subsequently assayed by HPLC using a C 18 column, and 1:1 (v/v) acetonitrile-water (adjusted to pH 4.0 with acetic acid 0.1%) as mobile phase. The quantification limit of piplartine was 0.2 μg/mL (0.6 μM), and the assay was linear up to 5 μg/mL (15.8 μM), with within-day and between-days assay coefficients of variation and relative errors <15%. Piplartine recovery from SC and VS varied from 86 to 96%. The method was suitable to assay samples from skin penetration studies, enabling detection of differences in cutaneous delivery in different skin compartments resulting from treatment with various formulations and time periods.

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Protein Transduction Domain-Containing Microemulsions as Cutaneous Delivery Systems for an Anticancer Agent

Cited by 41 publications

References 70 publications

Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel

Bioengineered Biomimetic and Bioinspired Noninvasive Drug Delivery Systems

Development of a method for quantitative determination of the cytotoxic agent piplartine (piperlongumine) in multiple skin layers

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