A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.
OBJECTIVE
Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release.


METHODS
Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC.


RESULTS
The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found.


CONCLUSIONS
The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.
Wu
Daocheng
D
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xian Jiaotong University, Xian 710049, China. wudaocheng@mail.xjtu.edu.cn
Wan
Mingxi
M
D000838:Anions / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D005459:Fluorides / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry; D000080385:Nanogels; D049329:Nanostructures; D036103:Nanotechnology; D010316:Particle Size; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D013678:Technology, Pharmaceutical; D014465:Ultrasonics
D000838:Anions; D000970:Antineoplastic Agents; D004337:Drug Carriers; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005780:Gelatin; D011094:Polyethyleneimine; D005459:Fluorides