Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

Anastasia Ripolin; Fabiana Volpe-Zanutto; Akmal H. Sabri; Victor Augusto Benedicto dos Santos; Sidney R. Figueroba; Arthur A.C. Bezerra; Brendo Vinicius Rodrigues Louredo; Pablo Agustin Vargas; Mary B. McGuckin; Aaron R.J. Hutton; Eneko Larrañeta; Michelle Franz-Montan; Ryan F. Donnelly

doi:10.1016/j.ijpharm.2024.124642

Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

Anastasia Ripolin, Fabiana Volpe-Zanutto, Akmal H. Sabri, Victor Augusto Benedicto dos Santos, Sidney R. Figueroba, Arthur A.C. Bezerra, Brendo Vinicius Rodrigues Louredo, Pablo Agustin Vargas, Mary B. McGuckin, Aaron R.J. Hutton, Eneko Larrañeta, Michelle Franz-Montan, Ryan F. Donnelly

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Abstract

As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs)
are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery of
BPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolving
and hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawley
rats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkaline
phosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls.
Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVX
controls and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. In
the distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21
% in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. This
proof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternative
for weekly osteoporosis management.

Original language	English
Article number	124642
Pages (from-to)	1-19
Number of pages	19
Journal	International journal of pharmaceutics
Volume	665
Early online date	28 Aug 2024
DOIs	https://doi.org/10.1016/j.ijpharm.2024.124642
Publication status	Published online - 28 Aug 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Keywords

Risedronate sodium
Alendronic acid
Dissolving microarray patches
Hydrogel-forming microarray patches
Transdermal
Osteoporosis

UN SDGs

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

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Cite this

Ripolin, A., Volpe-Zanutto, F., Sabri, A. H., Santos, V. A. B. D., Figueroba, S. R., Bezerra, A. A. C., Louredo, B. V. R., Vargas, P. A., McGuckin, M. B., Hutton, A. R. J., Larrañeta, E., Franz-Montan, M., & Donnelly, R. F. (2024). Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis. International journal of pharmaceutics, 665, 1-19. Article 124642. Advance online publication. https://doi.org/10.1016/j.ijpharm.2024.124642

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title = "Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis",

abstract = "As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs)are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery ofBPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolvingand hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawleyrats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkalinephosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls.Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVXcontrols and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. Inthe distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21% in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. Thisproof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternativefor weekly osteoporosis management.",

keywords = "Risedronate sodium, Alendronic acid, Dissolving microarray patches, Hydrogel-forming microarray patches, Transdermal, Osteoporosis",

author = "Anastasia Ripolin and Fabiana Volpe-Zanutto and Sabri, {Akmal H.} and Santos, {Victor Augusto Benedicto dos} and Figueroba, {Sidney R.} and Bezerra, {Arthur A.C.} and Louredo, {Brendo Vinicius Rodrigues} and Vargas, {Pablo Agustin} and McGuckin, {Mary B.} and Hutton, {Aaron R.J.} and Eneko Larra{\~n}eta and Michelle Franz-Montan and Donnelly, {Ryan F.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = aug,

day = "28",

doi = "10.1016/j.ijpharm.2024.124642",

language = "English",

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Ripolin, A, Volpe-Zanutto, F, Sabri, AH, Santos, VABD, Figueroba, SR, Bezerra, AAC, Louredo, BVR, Vargas, PA, McGuckin, MB, Hutton, ARJ, Larrañeta, E, Franz-Montan, M & Donnelly, RF 2024, 'Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis', International journal of pharmaceutics, vol. 665, 124642, pp. 1-19. https://doi.org/10.1016/j.ijpharm.2024.124642

TY - JOUR

T1 - Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

AU - Ripolin, Anastasia

AU - Volpe-Zanutto, Fabiana

AU - Sabri, Akmal H.

AU - Santos, Victor Augusto Benedicto dos

AU - Figueroba, Sidney R.

AU - Bezerra, Arthur A.C.

AU - Louredo, Brendo Vinicius Rodrigues

AU - Vargas, Pablo Agustin

AU - McGuckin, Mary B.

AU - Hutton, Aaron R.J.

AU - Larrañeta, Eneko

AU - Franz-Montan, Michelle

AU - Donnelly, Ryan F.

PY - 2024/8/28

Y1 - 2024/8/28

N2 - As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs)are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery ofBPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolvingand hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawleyrats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkalinephosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls.Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVXcontrols and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. Inthe distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21% in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. Thisproof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternativefor weekly osteoporosis management.

AB - As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs)are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery ofBPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolvingand hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawleyrats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkalinephosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls.Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVXcontrols and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. Inthe distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21% in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. Thisproof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternativefor weekly osteoporosis management.

KW - Risedronate sodium

KW - Alendronic acid

KW - Dissolving microarray patches

KW - Hydrogel-forming microarray patches

KW - Transdermal

KW - Osteoporosis

UR - https://doi.org/10.1016/j.ijpharm.2024.124642

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U2 - 10.1016/j.ijpharm.2024.124642

DO - 10.1016/j.ijpharm.2024.124642

M3 - Article

C2 - 39208953

SN - 0378-5173

VL - 665

SP - 1

EP - 19

JO - International journal of pharmaceutics

JF - International journal of pharmaceutics

M1 - 124642

ER -

Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

Abstract

Bibliographical note

Keywords

UN SDGs

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