Estradiol delivery

El Maghraby, G.M., A.C. Williams, and B.W. Barry. 2001. Skin hydration and possible shunt route penetration in controlled estradiol delivery from ultradeformable and standard liposomes. J Pharm Pharmacol 53 1311. 

The Estradiol to Cure Restenosis (ESTRACURE) trial is a randomized clinical trial of 360 patients undergoing stent implantation evaluating the efficacy and safety of local l7(3-estradiol delivery prior to stent implantation to reduce angiographic late luminal loss and restenosis, The hypothesis of this prospective, randomized, multicenter trial is that a single local administration of 17(3-estradiol will improve vascular healing and reduce late... 

Nash, H. A., Brache, V., Alvarez-Sanchez, F., Jackanicz,T. M., and Harmon,T. M. (1997), Estradiol delivery by vaginal rings Potential for hormone replacement therapy, Maturitas, 26, 27-33. 

The NuvaRing is a unique transvaginal delivery system that provides 15 meg ethinyl estradiol and 120 meg etonogestrel for the prevention of ovulation. The NuvaRing is inserted into the vagina on or before day 5 of the menstrual cycle and is removed... 

Other than possibly for the insensible perspiration they absorb, transdermal patches tend to operate as thermodynamically static systems, meaning as com-positionally fixed systems, from the moment they are applied until their removal. Marketed ethanol-driven estradiol and fentanyl patches are exceptions because they meter out ethanol and drive it into the stratum corneum to propel the absorption process. Compositional steadfastness is still the rule, however, and it is this feature that bestows the zero-order delivery attribute on the ordinary transdermal patch. Drug is present within the patches in reservoir amounts whether or not the reservoir compartment is easily distinguished, for there must be enough drug to sustain delivery over the full course of patch wear. 

W Im-Emsap, GA Brazeau, JW Simpkins, R Bodmeier. Sustained drug delivery of 17-/1 estradiol from injectable biodegradble in situ forming microparticles (ISM) system. AAPS PharmSci Supplement 2(4), AAPS Annual Meeting Abstracts, 2000. 

Brain delivery of steroid hormones is also of interest to medicinal chemists. Again, most data available on CDSs of steroids pertain to rates of oxidation of the dihydropyridine carrier, to blood and brain concentrations, and to pharmacological activities. The latter can then be taken as proof of efficient cerebral hydrolysis of the pyridinium metabolite. Thus, the dihydrotrigonelline carrier allowed good brain delivery of estradiol and some other estrogens [181][182],... 

Estradiol is formed by lithium aluminium hydride reduction of the ketone. We can formulate this simply as hydride acting as the nucleophile, though hydride delivery by LAH is strictly more complex than this. Unless you are specifically asked for details, treat LAH as a source of hydride ion. 

Continuous sequential regimen - It can be applied as a sequential regimen in combination with an estradiol-only transdermal delivery system. 

J. N. Simpkins, J. McCormack, K. S. Estes, M. E. Brewster, E. Sheck, N. Bodor (1986). Sustained brain-specific delivery of estradiol causes long-term suppression of luteinizing hormone secretion. J. Med. Chem. 29 1809-1812. 

Essa E, Bonner M, Barry B. Electrically assisted skin delivery of liposomal estradiol phospholipid as damage retardant. J Control Release 2004 95 535-546. 

Other types of drugs using this delivery system are clonidine and timolol (antihypertensives).estradiol (postmenopausal prophylaxis), fentanyl (opiate analgesic), and nicotine ("the patch"). 

Andersson TL, Stehle B, Davidsson B, Hoglund P. Bioavailability of estradiol from two matrix transdermal delivery systems Menorest and Climara. Maturitas 2000 34(l) 57-64. 

Bachmann G. Estradiol-releasing vaginal ring delivery system for urogenital atrophy. Experience over the past decade. I Reprod Med 1998 43(ll) 991-8. 

Al-Ghananeem, A. M., A. A. Traboulsi, L. W. Dittert, and A. A. Hussain. 2002. Targeted brain delivery of 17p-estradiol via nasally administered water soluble prodrAg S PharmSciTecllSiE5. 

Hofland et al. investigated the in vitro permeation behavior of estradiol from niosomes (rt-alkyl polyoxyethylenes/cholesterol) through human stratum corneum. In this study examining drug delivery from multilamellar niosomes, small unilamellar niosomes and a micellar solution, all being saturated systems containing 1.5, 1.5, and 0.75 mM estradiol, very low permeation fluxes were detected (64+17, 45 + 15, and 42 + 2 ng/cm2/h, respectively) [40]. 

FIGURE 17.1 Human epidermal penetration profiles of estradiol (n = 6) from ultradeformable liposomes from passive delivery and electroporation (5 pulses of 100 V, 100 ms, and 1 min spacing). 

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