Drug Delivery to the Cardiovascular System - Applications of Biotechnology in Cardiovascular Therapeutics - page 49

The NITRO-DUR Transdermal Infusion System (Schering-Plough) is a flat unit
designed to provide continuous controlled release of nitroglycerin through intact
skin. The rate of release of nitroglycerin is linearly dependent upon the area of the
applied system. Steady-state plasma concentrations of nitroglycerin are reached by
about 2 h after application of a patch and are maintained for the duration of wearing
the system. Upon removal of the patch, the plasma concentration declines with a
half-life of about an hour. Minitran Transdermal (3 M Pharmaceuticals) is also a
24 h transdermal nitroglycerin delivery system for prevention of angina pectoris
due to coronary artery disease. The onset of action of transdermal nitroglycerin is
not sufficiently rapid for this product to be useful in aborting an acute attack.
Trinipatch (Sanofi-Aventis) is a small, transparent, matrix, monolayer nitroglyc-
erin patch with an absorption promoter. Its systemic and local safety and clinical
efficacy have been studied in clinical trials. The systemic safety, assessed by
adverse event reporting, was good. A very good stability of cardiovascular param-
eters was observed, with no reflex tachycardia. The local safety, evaluated by the
Draize scale, was also satisfactory. A significant reduction of the number of angina
attacks and the numbers of doses of nitroglycerin was observed. The percentage of
pain-free patients increased from 18.2% at the start of the study to 76% at the end
of the trial. Trinipatch 5 mg is marketed now.
A new glyceryl trinitrate transdermal patch Epinitril (Rottapharm) contains the
drug uniformly dissolved in a monolayer pressure-sensitive acrylates vinyl acetate
copolymer adhesive matrix. The patch provides an intense flux rate of glyceryl
trinitrate through the skin. For its small size, thinness, flexibility, transparency,
easiness of application and of removal, and for its good tolerability, Epinitril is very
patient friendly, a quality that improves the compliance with the long-term thera-
peutic courses needed in angina pectoris.
Vaccines Delivery for Hypertension
Hypertension, which is one of the most common diseases of humans, is associated
to increased morbidity, mortality, and cost to society. However, hypertension is the
most common reversible risk factor for cardiovascular diseases. The renin-angiotensin
system (RAS) commands an important role in the regulation of blood pressure, and
so, at present, has been a target for clinical control by drugs acting on the system.
Despite the fact that effective drugs are available, blood pressure is successfully
controlled in only one third of the patients. Undesirable side effects and the poor
compliance with oral drug therapy are blamed for the poor results. Immunization
against renin and the angiotensins has been attempted in the past but the results
have not been satisfactory. Immunization against angiotensin-I with PMD-3117
vaccine, angiotensin-II with CYT006-AngQb vaccine, and targeting of angiotensin-
II type 1A receptor with ATR12181 vaccine have provided optimism in the devel-
opment of a hypertension vaccine (Pandey et al. 2009 ). Vaccines could induce