Preparation and characterization of marine sponge collagen nanoparticles and employment for the transdermal delivery of 17beta-estradiol-hemihydrate.
BACKGROUND
Transdermal administration of estradiol offers advantages over oral estrogens for hormone replacement therapy regarding side effects by bypassing the hepatic presystemic metabolism.


OBJECTIVE
The objective of this study was to develop nanoparticles of Chondrosia reniformis sponge collagen as penetration enhancers for the transdermal drug delivery of 17beta-estradiol-hemihydrate in hormone replacement therapy.


METHODS
Collagen nanoparticles were prepared by controlled alkaline hydrolysis and characterized using atomic force microscopy and photon correlation spectroscopy. Estradiol-hemihydrate was loaded to the nanoparticles by adsorption to their surface, whereupon a drug loading up to 13.1% of sponge collagen particle mass was found. After incorporation of drug-loaded nanoparticles in a hydrogel, the estradiol transdermal delivery from the gel was compared with that from a commercial gel that did not contain nanoparticles.


RESULTS
Saliva samples in postmenopausal patients showed significantly higher estradiol levels after application of the gel with nanoparticles. The area under the curve (AUC) for estradiol time-concentration curves over 24 hours was 2.3- to 3.4-fold higher and estradiol levels 24 hours after administration of estradiol were at least twofold higher with the nanoparticle gel.


CONCLUSIONS
The hydrogel with estradiol-loaded collagen nanoparticles enabled a prolonged estradiol release compared to a commercial gel and yielded a considerably enhanced estradiol absorption. Consequently, sponge collagen nanoparticles represent promising carriers for transdermal drug delivery.
KliniPharm GmbH, Frankfurt am Main, Germany.
Martina
M
Nicklas
Wolfgang
W
Schatton
Sascha
S
Heinemann
Thomas
T
Hanke
Jörg
J
Kreuter
D015502:Absorptiometry, Photon; D000279:Administration, Cutaneous; D000368:Aged; D000818:Animals; D001682:Biological Availability; D003094:Collagen / Q000737:chemistry*; D003956:Dialysis; D004337:Drug Carriers; D004563:Electrochemistry; D004958:Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005079:Excipients; D005260:Female; D006801:Humans; D020100:Hydrogels; D018625:Microscopy, Atomic Force; D008875:Middle Aged; D053758:Nanoparticles; D010316:Particle Size; D011161:Porifera / Q000737:chemistry*; D012463:Saliva / Q000378:metabolism; D013816:Thermodynamics
D004337:Drug Carriers; D005079:Excipients; D020100:Hydrogels; D004958:Estradiol; D003094:Collagen