Poly n-butylcyanoacrylate (PNBCA) nanocapsules as a carrier for NSAIDs: in vitro release and in vivo skin penetration.
OBJECTIVE
The aim of this work was to prepare poly n-butylcyanoacrylate (PNBCA) nanocapsules loaded with indomethacin and to evaluate the ability of this carrier system to deliver the drug systemically after its topical application.


METHODS
Poly n-butylcyanoacrylate (PNBCA) nanocapsules of indomethacin were prepared by interfacial polymerization. The physicochemical characterization of the PNBCA nanocapsules was performed by measuring the drug content by HPLC and analyzing the particle size using scanning electron microscopy. The in vitro permeation of indomethacin through excised rat skin and an artificial membrane was determined for PNBCA nanocapsules in pH 7.4 phosphate buffer (I), and in PLF-127 gel (II) and were compared against indomethacin incorporated into 25%w/w PLF-127 gel alone (III). The in vivo percutaneous absorption of indomethacin following the application of the PNBCA nanocapsules and a 25%w/w Pluronic F-127 (PLF-127) gel (III) was monitored by the determination of drug plasma levels in rats.


RESULTS
The drug loading results indicated that approximately 76.6% of indomethacin was loaded onto the PNBCA nanocapsules; the average particle size was 188 nm. The in vitro results indicated a rank order for the three formulations (I, II and III) in both the flux at steady state and the cumulative amounts permeated at 8 hrs. The higher drug plasma levels over 6 hrs of indomethacin PNBCA nanocapsules are in agreement with the determined in vitro permeation results.


CONCLUSIONS
The presented data show that indomethacin loaded PNBCA nanocapsules can improve the transdermal delivery of indomethacin compared to a conventional gel formulation using Pluronic F-127. This might be due to their ultra fine particle size and their hydrophilic and hydrophobic surface characteristics.
Miyazaki
Shozo
S
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tohbetsu, Hokkaido, Japan.
Takahashi
Akie
A
Kubo
Wataru
W
Bachynsky
John
J
Löebenberg
Raimar
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002214:Capsules / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004659:Enbucrilate / Q000737:chemistry*; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D036103:Nanotechnology; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D051381:Rats; D012869:Skin Absorption
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D004337:Drug Carriers; D020442:Poloxamer; D004659:Enbucrilate; D007213:Indomethacin