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Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders.

ABSTRACT: We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA)-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA-Do) HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA) and dodecylamine (Do) by varying the substitution ratio of Do to HA. The synthetic yield of HA-Do was more than 80% (HA-Do (A): 82.7 ± 4.7%, HA-Do (B): 87.1 ± 3.9% and HA-Do (C): 81.4 ± 4.5%). Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG) simultaneously self-assembled with HA-Do, and the size depended on the substitution ratio of Do in HA-Do (nanohydrogel (A): 118.0 ± 2.2 nm, nanohydrogel (B): 121.9 ± 11.4 nm, and nanohydrogel (C): 142.2 ± 3.8 nm). The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A) could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.

SUBMITTER: Son SU

PROVIDER: S-EPMC5746917 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders.

Son Seong Uk SU Lim Jae-Woo JW Kang Taejoon T Jung Juyeon J Lim Eun-Kyung EK

Nanomaterials (Basel, Switzerland) 20171204 12

We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA)-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA-Do) HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA) and dodecylamine (Do) by varying the substitution ratio of Do to HA. The synthetic yield of HA-Do was more than 80% (HA-Do (A): 82.7 ± 4.7%, HA-Do (B): 87.1 ± 3.9% and HA-Do (C): 81.4 ± 4.5%). Subsequently, nanohydrogels were ...[more]

PMID: 29207551

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Project description:The increment in ocular drug bioavailability after topical administration is one of the main challenges in pharmaceutical technology. For several years, different strategies based on nanotechnology, hydrogels or implants have been evaluated. Nowadays, the tolerance of ophthalmic preparations has become a critical issue and it is essential to the use of well tolerated excipients. In the present work, we have explored the potential of gelatin nanoparticles (GNPs) loaded with timolol maleate (TM), a beta-adrenergic blocker widely used in the clinic for glaucoma treatment and a hybrid system of TM-GNPs included in a hydroxypropyl methylcellulose (HPMC) viscous solution. The TM- loaded nanoparticles (mean particle size of 193 ± 20 nm and drug loading of 0.291 ± 0.019 mg TM/mg GNPs) were well tolerated both in vitro (human corneal cells) and in vivo. The in vivo efficacy studies performed in normotensive rabbits demonstrated that these gelatin nanoparticles were able to achieve the same hypotensive effect as a marketed formulation (0.5% TM) containing a 5-fold lower concentration of the drug. When comparing commercial and TM-GNPs formulations with the same TM dose, nanoparticles generated an increased efficacy with a significant (p < 0.05) reduction of intraocular pressure (IOP) (from 21% to 30%) and an augmentation of 1.7-fold in the area under the curve (AUC)(0-12h). On the other hand, the combination of timolol-loaded nanoparticles (TM 0.1%) and the viscous polymer HPMC 0.3%, statistically improved the IOP reduction up to 30% (4.65 mmHg) accompanied by a faster time of maximum effect (tmax = 1 h). Furthermore, the hypotensive effect was extended for four additional hours, reaching a pharmacological activity that lasted 12 h after a single instillation of this combination, and leading to an AUC(0-12h) 2.5-fold higher than the one observed for the marketed formulation. According to the data presented in this work, the use of hybrid systems that combine well tolerated gelatin nanoparticles and a viscous agent could be a promising alternative in the management of high intraocular pressure in glaucoma.

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Dataset Information

Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders.

Publications

Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders.

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