Defining optimal permeant characteristics for ultrasound-mediated gastrointestinal delivery.
J Control Release
; 268: 113-119, 2017 Dec 28.
Article
em En
| MEDLINE
| ID: mdl-29051063
ABSTRACT
Ultrasound-mediated drug delivery in the gastrointestinal (GI) tract is a bourgeoning area of study. Localized, low-frequency ultrasound has recently been shown to enable significant enhancement in delivery of a broad set of active pharmaceutical ingredients including small molecules, proteins, and nucleic acids without any formulation or encapsulation of the therapeutic. Traditional chemical formulations are typically required to protect, stabilize, and enable the successful delivery of a given therapeutic. The use of ultrasound, however, may make delivery insensitive to the chemical formulation. This might open the door to chemical formulations being developed to address other properties besides the deliverability of a therapeutic. Instead, chemical formulations could potentially be developed to achieve novel pharmacokinetics, without consideration of that particular formulation's ability to penetrate the mucus barrier passively. Here we investigated the effect of permeant size, charge, and the presence of chemical penetration enhancers on delivery to GI tissue using ultrasound. Short ultrasound treatments enabled delivery of large permeants, including microparticles, deep into colonic tissue ex vivo. Delivery was relatively independent of size and charge but did depend on conformation, with regular, spherical particles being delivered to a greater extent than long-chain polymers. The subsequent residence time of model permeants in tissue after ultrasound-mediated delivery was found to depend on size, with large microparticles demonstrating negligible clearance from the local tissue 24h after delivery ex vivo. The dependence of clearance time on permeant size was further confirmed in vivo in mice using fluorescently labeled 3kDa and 70kDa dextran. The use of low-frequency ultrasound in the GI tract represents a novel tool for the delivery of a wide-range of therapeutics independent of formulation, potentially allowing for the tailoring of formulations to impart novel pharmacokinetic profiles once delivered into tissue.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
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Colo
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Ondas Ultrassônicas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article