Drug transport kinetics of intravascular triggered drug delivery systems.
Commun Biol
; 4(1): 920, 2021 07 28.
Article
em En
| MEDLINE
| ID: mdl-34321602
ABSTRACT
Intravascular triggered drug delivery systems (IV-DDS) for local drug delivery include various stimuli-responsive nanoparticles that release the associated agent in response to internal (e.g., pH, enzymes) or external stimuli (e.g., temperature, light, ultrasound, electromagnetic fields, X-rays). We developed a computational model to simulate IV-DDS drug delivery, for which we quantified all model parameters in vivo in rodent tumors. The model was validated via quantitative intravital microscopy studies with unencapsulated fluorescent dye, and with two formulations of temperature-sensitive liposomes (slow, and fast release) encapsulating a fluorescent dye as example IV-DDS. Tumor intra- and extravascular dye concentration dynamics were extracted from the intravital microscopy data by quantitative image processing, and were compared to computer model results. Via this computer model we explain IV-DDS delivery kinetics and identify parameters of IV-DDS, of drug, and of target tissue for optimal delivery. Two parameter ratios were identified that exclusively dictate how much drug can be delivered with IV-DDS, indicating the importance of IV-DDS with fast drug release (~sec) and choice of a drug with rapid tissue uptake (i.e., high first-pass extraction fraction). The computational model thus enables engineering of improved future IV-DDS based on tissue parameters that can be quantified by imaging.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
/
Desenvolvimento de Medicamentos
/
Neoplasias
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article