Permeation enhancer-containing water-in-oil nanoemulsions as carriers for intravesical cisplatin delivery.
OBJECTIVE
In the present work, we developed water-in-oil (w/o) nanoemulsions for the intravesical administration of cisplatin.


METHODS
The nanoemulsions were made up of soybean oil as the oil phase and Span 80, Tween 80, or Brij 98 as the emulsifier system. alpha-Terpineol and oleic acid were incorporated as permeation enhancers. The physicochemical characteristics of droplet size, zeta potential, and viscosity were determined. Nanoemulsions were administered intravesically for 1 approximately 4 h to rats in vivo. Animals were subsequently sacrificed, and the bladders were harvested to examine drug accumulation and histology.


RESULTS
Ranges of the mean size and zeta potential were 30 approximately 90 nm and -3.4 to -9.3 mV, respectively. The addition of enhancers further reduced the size of the nanoemulsions. The viscosity of all systems exhibited Newtonian behavior. The cisplatin-loaded nanoemulsions were active against bladder cancer cells. The nanoemulsions with Brij 98 exhibited the complete inhibition of cell proliferation. The encapsulation of cisplatin and carboplatin, another derivative of cisplatin, in nanoemulsions resulted in slower and more-sustained release. The amount of drug which permeated into bladder tissues significantly increased when using carriers containing Brij 98, with the alpha-terpineol-containing formulation showing the best result. The nanoemulsion with alpha-terpineol prolonged the duration of higher drug accumulation to 3 approximately 4 h. At the later stage of administration (3 approximately 4 h), this system increased the bladder wall deposition of cisplatin and carboplatin by 2.4 approximately 3.3-fold compared to the control solution. Histological examination of the urothelium showed near-normal morphology in rats instilled with these nanoemulsions. alpha-Terpineol possibly caused slight desquamation of umbrella cells.


CONCLUSIONS
The nanoemulsions are feasible to load cisplatin for intravesical drug delivery.
Hwang
Tsong-Long
TL
Cell Pharmacology Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Fang
Chia-Lang
CL
Chen
Chao-Huang
CH
Fang
Jia-You
JY
D000283:Administration, Intravesical; D000818:Animals; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D005260:Female; D006801:Humans; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D014867:Water / Q000008:administration & dosage* / Q000378:metabolism
D004655:Emulsions; D014867:Water; D013024:Soybean Oil; D002945:Cisplatin