Ocular Cubosome Drug Delivery System for Timolol Maleate: Preparation, Characterization, Cytotoxicity, Ex Vivo, and In Vivo Evaluation

Autor: Tingting Peng, Chuan-Yu Wu, Youmei Zeng, Jiayuan Huang, Yanrong Li, Chuanbin Wu, Ying Huang, Xin Pan, Zhengwen Zhan
Rok vydání: 2017
Předmět:
Intraocular pressure
genetic structures
Adrenergic beta-Antagonists
Drug Evaluation
Preclinical
Pharmaceutical Science
Glaucoma
Administration
Ophthalmic
02 engineering and technology
Aquatic Science
Pharmacology
030226 pharmacology & pharmacy
Cornea
03 medical and health sciences
Drug Delivery Systems
0302 clinical medicine
X-Ray Diffraction
In vivo
Scattering
Small Angle
Drug Discovery
medicine
Zeta potential
Animals
Humans
Particle Size
Intraocular Pressure
Ecology
Evolution
Behavior and Systematics
Ecology
Chemistry
General Medicine
021001 nanoscience & nanotechnology
medicine.disease
eye diseases
Bioavailability
Drug delivery
Poloxamer 407
Timolol
Female
Rabbits
sense organs
Ophthalmic Solutions
0210 nano-technology
Agronomy and Crop Science
Ex vivo
Biomedical engineering
medicine.drug
Zdroj: AAPS PharmSciTech. 18:2919-2926
ISSN: 1530-9932
DOI: 10.1208/s12249-017-0763-8
Popis: Glaucoma is an ocular disease featuring increased intraocular pressure (IOP) and its primary treatment strategy is to lower IOP by medication. Current ocular drug delivery in treating glaucoma is confronting a variety of challenges, such as low corneal permeability and bioavailability due to the unique anatomical structure of the human eye. To tackle these challenges, a cubosome drug delivery system for glaucoma treatment was constructed for timolol maleate (TM) in this study. The TM cubosomes (liquid crystalline nanoparticles) were prepared using glycerol monooleate and poloxamer 407 via high-pressure homogenization. These constructed nanoparticles appeared spherical using transmission electron microscopy and had an average particle size of 142 nm, zeta potential of -6.27 mV, and over 85% encapsulation efficiency. Moreover, using polarized light microscopy and small-angle X-ray scattering (SAXS), it was shown that the TM cubosomes have cubic liquid crystalline D-type (Pn3m) structure, which provides good physicochemical stability and high encapsulation efficiency. Ex vivo corneal permeability experiments showed that the total amount of TM cubosomes penetrated was higher than the commercially available eye drops. In addition, in vivo studies revealed that TM cubosomes reduced the IOP in rabbits from 27.8∼39.7 to 21.4∼32.6 mmHg after 1-week administration and had a longer retention time and better lower-IOP effect than the commercial TM eye drops. Furthermore, neither cytotoxicity nor histological impairment in the rabbit corneas was observed. This study suggests that cubosomes are capable of increasing the corneal permeability and bioavailability of TM and have great potential for ocular disease treatment.
Databáze: OpenAIRE
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