Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin

Xiulian Jesmine Cai; Patrick Mesquida; Stuart Allen Jones

doi:10.1016/j.ijpharm.2016.08.055

Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin

Xiulian Jesmine Cai, Patrick Mesquida, Stuart Allen Jones

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Abstract

Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99 ± 7.96 μg/cm2/h) compared to the xanthan gum (1.16 ± 0.14 μg/cm2/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95 ± 28.63 μg/cm2/h) compared to the equivalent xanthan gum system (14.19 ± 2.27 μg/cm2/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather they were a consequence of the dehydration induced diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.

Original language	English
Journal	INTERNATIONAL JOURNAL OF PHARMACEUTICS
Early online date	28 Aug 2016
DOIs	https://doi.org/10.1016/j.ijpharm.2016.08.055
Publication status	E-pub ahead of print - 28 Aug 2016

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10.1016/j.ijpharm.2016.08.055

Investigating the ability of nanoparticle_CAI_Accepted26August2016_GREEN AAMAccepted author manuscript, 616 KBLicence: CC BY-NC-ND

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@article{cca36b85cb3f457e9818af2ee3875443,

title = "Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin",

abstract = "Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99 ± 7.96 μg/cm2/h) compared to the xanthan gum (1.16 ± 0.14 μg/cm2/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95 ± 28.63 μg/cm2/h) compared to the equivalent xanthan gum system (14.19 ± 2.27 μg/cm2/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather they were a consequence of the dehydration induced diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.",

author = "Cai, {Xiulian Jesmine} and Patrick Mesquida and Jones, {Stuart Allen}",

year = "2016",

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doi = "10.1016/j.ijpharm.2016.08.055",

language = "English",

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AU - Cai, Xiulian Jesmine

AU - Mesquida, Patrick

AU - Jones, Stuart Allen

PY - 2016/8/28

Y1 - 2016/8/28

N2 - Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99 ± 7.96 μg/cm2/h) compared to the xanthan gum (1.16 ± 0.14 μg/cm2/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95 ± 28.63 μg/cm2/h) compared to the equivalent xanthan gum system (14.19 ± 2.27 μg/cm2/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather they were a consequence of the dehydration induced diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.

AB - Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99 ± 7.96 μg/cm2/h) compared to the xanthan gum (1.16 ± 0.14 μg/cm2/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95 ± 28.63 μg/cm2/h) compared to the equivalent xanthan gum system (14.19 ± 2.27 μg/cm2/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather they were a consequence of the dehydration induced diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.

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DO - 10.1016/j.ijpharm.2016.08.055

M3 - Article

SN - 0378-5173

JO - INTERNATIONAL JOURNAL OF PHARMACEUTICS

JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS

ER -

Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin

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