Mechanistic investigation of transcutaneous protein delivery using solid-in-oil nanodispersion: A case study with phycocyanin

Hardiningtyas, Safrina Dyah; Wakabayashi, Rie; Kitaoka, Momoko; Tahara, Yoshiro; Minamihata, Kosuke; Goto, Masahiro; Kamiya, Noriho

doi:10.1016/j.ejpb.2018.01.020

Cited by 14 publications

(8 citation statements)

References 29 publications

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“…While DLC-SON showed a smaller particle size in comparison to DLC-control (P<0.05) since L195 is highly soluble in the organic phase (cyclohexane) and has a low HLB value (≈ 1). 45 The same results were observed with Boswellic acid conjugated vesicles. 46 VEM was classified as a Class IV drug (low solubility and low permeability).…”

Section: Characterization Of the Prepared Dlc-sonsupporting

confidence: 68%

Modified solid in oil nanodispersion containing vemurafenib-lipid complex-in vitro/in vivo study

2022

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Background: Vemurafenib (VEM) was a licensed drug for the treatment of skin melanoma and is available only in the market as oral tablets prescribed in huge doses (1920 mg/day). One reason for the high dose is vemurafenib's low oral bioavailability. Methods: VEM-lipid complex (DLC) was predicted based on Conquest and Mercury programs and prepared using the solvent evaporation method using the lipid (phosphatidylethanolamine). DLC was subjected to characterization (FT-IR, Raman spectroscopy, DSC, TGA, P-XRD, and FESEM) to confirm complexation. DLC was used to prepare solid in oil nanodispersion (DLC-SON) and subjected to in vitro, ex vivo, and in vivo evaluation in comparison to our recently prepared conventional SON (VEM-SON) and DLC-control. Results: Conquest and Mercury predict the availability of intermolecular hydrogen bonding between VEM and phosphatidylethanolamine (PE). All characterization tests of DLC ensure the complexation of the drug with PE. Ex vivo studies showed that the drug in DLC-SON has significantly (P<0.05) higher skin permeation than DLC-control but lower drug permeation than conventional SON but it has a higher % skin deposition (P<0.05) than others. The half-maximal inhibitory concentration (IC50) of the prepared DLC-SON is significantly high (P<0.05) in comparison to the conventional SON and pure VEM. In vivo permeation using confocal laser scanning microscopy (on the rat) results indicated that both conventional SON and DLC-SON can cross the SC and infiltrate the dermis and epidermis but DLC-SON has a higher luminance/gray value after 24 h in the dermis in comparison to the conventional SON. Conclusion: The novel lipid complex for VEM prepared using PE as a lipid and enclosed in SON showed higher anticancer activity and topical permeation as well as sustained delivery and good retention time in the dermis that localize the drug in a sufficient concentration to eliminate early diagnosed skin melanoma.

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Section: Characterization Of the Prepared Dlc-sonsupporting

confidence: 68%

Modified solid in oil nanodispersion containing vemurafenib-lipid complex-in vitro/in vivo study

2022

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“…They are prepared by freezedrying water-in-oil emulsions containing therapeutic cargo followed by dispersion of the surfactant-medicine complexes into an oil vehicle that has affinity to the SC 50 . This system is attractive as a nanocarrier for peptides such as antigens and vaccine components owing to the high encapsulation efficacy for hydrophilic molecules and capacity for co-loading immunomodulatory agents like adjuvants [51][52][53] .…”

Section: Solid-in-oil Systemsmentioning

confidence: 99%

Section: Noninvasive Transcutaneous Immunizationmentioning

confidence: 99%

“…50 This system is attractive as a nanocarrier for peptides such as antigens and vaccine components owing to the high encapsulation efficacy for hydrophilic molecules and capacity for coloading immunomodulatory agents like adjuvants. [51][52][53] Recently, Kitaoka et al 54 used a S/O nanodispersion system to deliver both the hydrophilic allergen molecules (β-lactoglobulin) and the lyophilic adjuvant (R-848) through the epidermis. The authors applied isopropyl myristate as an oil vehicle in the S/O nanodispersion and sucrose laurate L-195 as a surfactant.…”

Section: Solid-in-oil Systemsmentioning

confidence: 99%

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Formulation‐based approaches for dermal delivery of vaccines and therapeutic nucleic acids: Recent advances and future perspectives

Sallam

Prakash

Kumbhojkar

et al. 2021

Bioengineering & Transla Med

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A growing variety of biological macromolecules are in development for use as active ingredients in topical therapies and vaccines. Dermal delivery of biomacromolecules offers several advantages compared to other delivery methods, including improved targetability, reduced systemic toxicity and decreased degradation of drugs. However, this route of delivery is hampered by the barrier function of the skin. Recently, a large body of research has been directed towards improving the delivery of macromolecules to the skin, ranging from nucleic acids to antigens, using noninvasive means. In this review, we discuss the latest formulation-based efforts to deliver antigens and nucleic acids for vaccination and treatment of skin diseases. We provide a perspective of their advantages, limitations and potential for clinical translation. The delivery platforms discussed in this review may provide formulation scientists and clinicians with a better vision of the alternatives for dermal delivery of biomacromolecules, which may facilitate the development of new patientfriendly prophylactic and therapeutic medicines.

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“…Delivering hydrophilic proteins via the skin is challenging because of the inherent barrier effect of the skin ( Anselmo et al, 2019 ). In response to the skin barrier problem, previous studies have successfully enhanced the penetration of protein-based drugs into the skin by using solids-in-oil (S/O) nanodispersion systems ( Tahara et al, 2008 ; Hardiningtyas et al, 2018 ; Hardiningtyas et al, 2019 ). In in vitro skin penetration studies, Safrina et al developed a C-PC transdermal protein delivery system based on S/O nanodispersion technology and found that it promoted C-PC delivery through the cuticle layer of Yucatan micropig skin ( Hardiningtyas et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The anti-photoaging effect of C-phycocyanin on ultraviolet B-irradiated BALB/c-nu mouse skin

Zhou,

Bai,

Huang

et al. 2023

Front. Bioeng. Biotechnol.

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Introduction: C-phycocyanin (C-PC), a photosynthetic protein obtained from Spirulina, is regarded a highly promising commercially available biochemical. Numerous in vitro and in vivo studies have provided evidence of C-PC’s ability to mitigate the inflammatory response, alleviate oxidative stress, and facilitate wound healing. However, despite the existing knowledge regarding C-PC’s protective mechanism against cellular apoptosis induced by ultraviolet B (UVB) radiation, further in vivo experiments are needed to explore its anti-photoaging mechanism.Methods: In this study, a UVB-induced skin photoaging model was established using BALB/c-nu mice, and the potential protective effects of topically administered c-PC were investigated by various molecular biology tools. In addition, a novel delivery system, C-PC nanodispersion, was developed to facilitate the transdermal delivery of C-PC.Results: C- PC demonstrated significant anti-photoaging activities in the UVB-induced skin. The application of C-PC to the dorsal skin of the mice resulted in improved macroscopic characteristics, such as reduced sagging and coarse wrinkling, under UVB irradiation Histological analyses showed that C-PC treatment significantly decreased the symptoms of epidermal thickening, prevented dermal collagen fiber loosening, increased the hydroxyproline (Hyp) content and activities of antioxidant enzymes (such as superoxide dismutase, catalase, and glutathione peroxidase) in mouse skin, decreased malondialdehyde levels and expressions of inflammatory factors (interleukin-1α [IL-1α], IL-1β, IL-6, and tumor necrosis factor-α), reduced matrix metalloproteinase [MMP-3 and MMP-9] expressions, and inhibited the phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38 proteins in the mitogen-activated protein kinase family.Discussion: By analyzing the results of the study, a new drug delivery system, C-PC nano-dispersion, was proposed, and the anti-photoaging effect of C-PC and its mechanism were investigated.

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Mechanistic investigation of transcutaneous protein delivery using solid-in-oil nanodispersion: A case study with phycocyanin

Cited by 14 publications

References 29 publications

Modified solid in oil nanodispersion containing vemurafenib-lipid complex-in vitro/in vivo study

Modified solid in oil nanodispersion containing vemurafenib-lipid complex-in vitro/in vivo study

Formulation‐based approaches for dermal delivery of vaccines and therapeutic nucleic acids: Recent advances and future perspectives

The anti-photoaging effect of C-phycocyanin on ultraviolet B-irradiated BALB/c-nu mouse skin

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