Microprocessor-controlled iontophoretic drug delivery of 5-fluorouracil: pharmacodynamic and pharmacokinetic study.
OBJECTIVE
The purpose of this study was to fabricate monolithic 5-fluorouracil (5-FU) transdermal patch with microprocessor- controlled iontophoretic delivery, to evaluate the pharmacodynamic effects on Dalton's lymphoma ascites (DLA) induced in Balb/c mice, and to study pharmacokinetics in rabbits.


METHODS
The transdermal patches were prepared by solvent casting method; a reprogrammable microprocessor was developed and connected to the patches. DLA cells were injected to the hind limb of Balb/c mice (10 animals/group). In the first group of mice 5-FU was administered i.v. (12 mg/kg). In the second group of mice, transdermal patches (20 mg/patch/animal) were installed and kept for 10 consecutive days, while the third (control) group was kept without any treatment. The tumor diameter was measured every 5th day for 30 days, and the animal survival time and death pattern were studied. The electric current density protocol of 0.5 mA/cm(2) for 30 min was used in the pharmacokinetic study in rabbits.


RESULTS
There was a significant reduction in tumor volume in the animals treated with monolithic matrix 5-FU transdermal patch compared to untreated controls and i.v. therapy. Tumor volume of the control animals was 5.8 cm(3) on the 30th day, while in 5-FU with transdermal patch delivery animals it was only 0.23 cm(3) (p <0.05). DLA cells tumor-bearing mice treated with 5-FU with transdermal patch had significantly increased lifespan (ILS). Control animals survived only 21+/-1 days after the tumor inoculation, while i.v. 5-FU and 5-FU patches animals survived 24+/-2.7 days and 39.5+/-1.87 days with ILS of 25.58% and 88.09%, respectively (p <0.01). There was significant sustained release of 5-FU through microprocessor-controlled patches and half-life was significantly higher (p <0.05) compared to the i.v. route.


CONCLUSIONS
Cytotoxic concentration of 5-FU can be achieved through the transdermal drug delivery and effective therapeutic drug concentration can be maintained up to 24 h, with less toxicity. A new generation of transdermal drug delivery systems based on microprocessor-controlled iontophoresis is in the late stages of development and promises to enhance the treatment of local and systemic medical conditions. The incorporation of microprocessor into these systems has been an important advancement to ensure safe and efficient administration of a wide variety of drugs.
Chandrashekar
N S
NS
Al-Ameen College of Pharmacy, Bangalore, India. nschandrashekar@gmail.com
Shobha Rani
R H
RH
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001201:Ascites / Q000178:diet therapy / Q000209:etiology; D016503:Drug Delivery Systems / Q000379:methods*; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D007476:Ionophores / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008223:Lymphoma / Q000150:complications / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008838:Microcomputers; D011817:Rabbits
D000964:Antimetabolites, Antineoplastic; D007476:Ionophores; D005472:Fluorouracil