Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer

Heba Abd-El-Azim; Ismaiel A. Tekko; Ahlam Ali; Alyaa Ramadan; Noha Nafee; Nawal Khalafallah; Taifur Rahman; William Mcdaid; Rania G. Aly; Lalitkumar K. Vora; Steven J. Bell; Fiona Furlong; Helen O. McCarthy; Ryan F. Donnelly

doi:10.1016/j.jconrel.2022.06.027

Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer

Heba Abd-El-Azim, Ismaiel A. Tekko, Ahlam Ali, Alyaa Ramadan, Noha Nafee, Nawal Khalafallah, Taifur Rahman, William Mcdaid, Rania G. Aly, Lalitkumar K. Vora, Steven J. Bell, Fiona Furlong, Helen O. McCarthy, Ryan F. Donnelly^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

65 Citations (Scopus)

165 Downloads (Pure)

Abstract

Photodynamic therapy (PDT) to manage non-melanoma skin cancers has garnered great attention over the past few years. Hypericin (Hy) is a potent lipid-soluble photosensitiser with promising anticancer therapeutic activities. Nevertheless, its poor water-solubility, aggregation in biological systems and insufficient skin penetration restricted its effective exploitation. Herein, we report for the first-time encapsulation of Hy into lipid nanocapsules (Hy-LNCs), and then application of an AdminPen™ hollow microneedles (Ho-MNs) array and an in-house fabricated Ho-MN to enable efficient intradermal delivery. The physicochemical properties, photoactivity, ex vivo drug distribution and cellular uptake were evaluated. Results showed that Hy-LNCs were successfully formed with a particle size of 47.76 ± 0.49 nm, PDI of 0.12 ± 0.02, high encapsulation efficiency (99.67% ± 0.35), 396 fold higher photoactivity, 7 fold higher skin drug deposition, significantly greater cellular uptake and higher photocytotoxicity compared to free Hy. The therapeutic effect of Hy-LNCs was finally assessed in vivo using a nude mouse model with transplanted tumours. Interestingly, Hy-LNCs delivered by Ho-MN exhibited remarkable anti-tumour destruction (85.84%) after irradiation with 595 nm. This study showed that Ho-MNs-driven delivery of Hy-LNCs followed by irradiation could form a promising minimally invasive, effective and site-specific approach for managing non-melanoma skin cancers.

Original language	English
Pages (from-to)	849-869
Number of pages	21
Journal	Journal of Controlled Release
Volume	348
Early online date	28 Jun 2022
DOIs	https://doi.org/10.1016/j.jconrel.2022.06.027
Publication status	Published - Aug 2022

Keywords

Non-melanoma skin cancer, hypericin
Lipid nanocapsule, hollow microneedle
Photodynamic therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jconrel.2022.06.027Licence: CC BY

Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer
Copyright 2022 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 5.72 MBLicence: CC BY

Cite this

Abd-El-Azim, H., Tekko, I. A., Ali, A., Ramadan, A., Nafee, N., Khalafallah, N., Rahman, T., Mcdaid, W., Aly, R. G., Vora, L. K., Bell, S. J., Furlong, F., McCarthy, H. O., & Donnelly, R. F. (2022). Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer. Journal of Controlled Release, 348, 849-869. https://doi.org/10.1016/j.jconrel.2022.06.027

@article{18cc476786664e118fdd5576ba39cf17,

title = "Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer",

abstract = "Photodynamic therapy (PDT) to manage non-melanoma skin cancers has garnered great attention over the past few years. Hypericin (Hy) is a potent lipid-soluble photosensitiser with promising anticancer therapeutic activities. Nevertheless, its poor water-solubility, aggregation in biological systems and insufficient skin penetration restricted its effective exploitation. Herein, we report for the first-time encapsulation of Hy into lipid nanocapsules (Hy-LNCs), and then application of an AdminPen{\texttrademark} hollow microneedles (Ho-MNs) array and an in-house fabricated Ho-MN to enable efficient intradermal delivery. The physicochemical properties, photoactivity, ex vivo drug distribution and cellular uptake were evaluated. Results showed that Hy-LNCs were successfully formed with a particle size of 47.76 ± 0.49 nm, PDI of 0.12 ± 0.02, high encapsulation efficiency (99.67% ± 0.35), 396 fold higher photoactivity, 7 fold higher skin drug deposition, significantly greater cellular uptake and higher photocytotoxicity compared to free Hy. The therapeutic effect of Hy-LNCs was finally assessed in vivo using a nude mouse model with transplanted tumours. Interestingly, Hy-LNCs delivered by Ho-MN exhibited remarkable anti-tumour destruction (85.84%) after irradiation with 595 nm. This study showed that Ho-MNs-driven delivery of Hy-LNCs followed by irradiation could form a promising minimally invasive, effective and site-specific approach for managing non-melanoma skin cancers. ",

keywords = "Non-melanoma skin cancer, hypericin, Lipid nanocapsule, hollow microneedle, Photodynamic therapy",

author = "Heba Abd-El-Azim and Tekko, {Ismaiel A.} and Ahlam Ali and Alyaa Ramadan and Noha Nafee and Nawal Khalafallah and Taifur Rahman and William Mcdaid and Aly, {Rania G.} and Vora, {Lalitkumar K.} and Bell, {Steven J.} and Fiona Furlong and McCarthy, {Helen O.} and Donnelly, {Ryan F.}",

year = "2022",

month = aug,

doi = "10.1016/j.jconrel.2022.06.027",

language = "English",

volume = "348",

pages = "849--869",

journal = "Journal of Controlled Release",

issn = "1873-4995",

publisher = "Elsevier B.V.",

}

Abd-El-Azim, H, Tekko, IA, Ali, A, Ramadan, A, Nafee, N, Khalafallah, N, Rahman, T, Mcdaid, W, Aly, RG, Vora, LK , Bell, SJ , Furlong, F , McCarthy, HO & Donnelly, RF 2022, 'Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer', Journal of Controlled Release, vol. 348, pp. 849-869. https://doi.org/10.1016/j.jconrel.2022.06.027

TY - JOUR

T1 - Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer

AU - Abd-El-Azim, Heba

AU - Tekko, Ismaiel A.

AU - Ali, Ahlam

AU - Ramadan, Alyaa

AU - Nafee, Noha

AU - Khalafallah, Nawal

AU - Rahman, Taifur

AU - Mcdaid, William

AU - Aly, Rania G.

AU - Vora, Lalitkumar K.

AU - Bell, Steven J.

AU - Furlong, Fiona

AU - McCarthy, Helen O.

AU - Donnelly, Ryan F.

PY - 2022/8

Y1 - 2022/8

N2 - Photodynamic therapy (PDT) to manage non-melanoma skin cancers has garnered great attention over the past few years. Hypericin (Hy) is a potent lipid-soluble photosensitiser with promising anticancer therapeutic activities. Nevertheless, its poor water-solubility, aggregation in biological systems and insufficient skin penetration restricted its effective exploitation. Herein, we report for the first-time encapsulation of Hy into lipid nanocapsules (Hy-LNCs), and then application of an AdminPen™ hollow microneedles (Ho-MNs) array and an in-house fabricated Ho-MN to enable efficient intradermal delivery. The physicochemical properties, photoactivity, ex vivo drug distribution and cellular uptake were evaluated. Results showed that Hy-LNCs were successfully formed with a particle size of 47.76 ± 0.49 nm, PDI of 0.12 ± 0.02, high encapsulation efficiency (99.67% ± 0.35), 396 fold higher photoactivity, 7 fold higher skin drug deposition, significantly greater cellular uptake and higher photocytotoxicity compared to free Hy. The therapeutic effect of Hy-LNCs was finally assessed in vivo using a nude mouse model with transplanted tumours. Interestingly, Hy-LNCs delivered by Ho-MN exhibited remarkable anti-tumour destruction (85.84%) after irradiation with 595 nm. This study showed that Ho-MNs-driven delivery of Hy-LNCs followed by irradiation could form a promising minimally invasive, effective and site-specific approach for managing non-melanoma skin cancers.

AB - Photodynamic therapy (PDT) to manage non-melanoma skin cancers has garnered great attention over the past few years. Hypericin (Hy) is a potent lipid-soluble photosensitiser with promising anticancer therapeutic activities. Nevertheless, its poor water-solubility, aggregation in biological systems and insufficient skin penetration restricted its effective exploitation. Herein, we report for the first-time encapsulation of Hy into lipid nanocapsules (Hy-LNCs), and then application of an AdminPen™ hollow microneedles (Ho-MNs) array and an in-house fabricated Ho-MN to enable efficient intradermal delivery. The physicochemical properties, photoactivity, ex vivo drug distribution and cellular uptake were evaluated. Results showed that Hy-LNCs were successfully formed with a particle size of 47.76 ± 0.49 nm, PDI of 0.12 ± 0.02, high encapsulation efficiency (99.67% ± 0.35), 396 fold higher photoactivity, 7 fold higher skin drug deposition, significantly greater cellular uptake and higher photocytotoxicity compared to free Hy. The therapeutic effect of Hy-LNCs was finally assessed in vivo using a nude mouse model with transplanted tumours. Interestingly, Hy-LNCs delivered by Ho-MN exhibited remarkable anti-tumour destruction (85.84%) after irradiation with 595 nm. This study showed that Ho-MNs-driven delivery of Hy-LNCs followed by irradiation could form a promising minimally invasive, effective and site-specific approach for managing non-melanoma skin cancers.

KW - Non-melanoma skin cancer, hypericin

KW - Lipid nanocapsule, hollow microneedle

KW - Photodynamic therapy

U2 - 10.1016/j.jconrel.2022.06.027

DO - 10.1016/j.jconrel.2022.06.027

M3 - Article

C2 - 35728715

SN - 1873-4995

VL - 348

SP - 849

EP - 869

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this