Abstract
Due to their effect of vasodilatation, isosorbide nitrates represent one of the most important and most used solutions for angina pectoris. Unfortunately, these compounds have multiple dose-related adverse drug reactions such as headache, weakness, mild dizziness, and occasionally heart rate changes, nausea, vomiting, and sweating. The main aims of this research were to obtain and to evaluate new polyurethane (PU) structures that can be used as a proper transmembrane carrier with an improved release kinetic. Chitosan-based PU structures were obtained by a polyaddition process between hexamethylene diisocyanate and a mixture of chitosan, butanediol, and polyethylene glycol in the presence of caffeine as a synthesis catalyst. The obtained samples (with and without isosorbide nitrates) were characterized regarding the encapsulation and release rate (UV-Vis spectra), chemical composition (FTIR), thermal stability (thermal analysis), morphology changes (SEM and SANS), and in vivo irritation tests. These methods revealed no significant differences between the two sample structures. Multipopulational structures with sizes between 73 and 310 nm, with an increased tendency to form clusters and a high resistance to heat (up to 280°C), were obtained. This study presents an alternative administration of isosorbide derivatives based on a PU carrier with a high biocompatibility and a prolonged release.
Highlights
IntroductionNitrate medications (nitroglycerin, sodium nitroprusside, isosorbide derivatives, etc.) are pharmaceutical agents with vasodilator effect (Polakowska et al, 2016)
Nitrate medications are pharmaceutical agents with vasodilator effect (Polakowska et al, 2016)
Three-dimensional PU structures are often found among those materials that are preferably used in medical applications due to their easy and cheap production as well as to their unique combination of biocompatibility, sterilizability, durability, good mechanical properties, abrasion, and chemical resistance (Kikuchi et al, 2017)
Summary
Nitrate medications (nitroglycerin, sodium nitroprusside, isosorbide derivatives, etc.) are pharmaceutical agents with vasodilator effect (Polakowska et al, 2016). Medication with isosorbide nitrates as active compounds is often used to prevent angina attacks and in the prophylactic treatments of angina pectoris (Yao et al, 2015). Rodgers reported a series of problems due to the administration of isosorbide nitrates: 82% of patients accused headaches and ∼10% could not tolerate them due to dizziness and/or disabling headaches; severe hypotension cases accompanied by syncope were recorded; the combination of nitrates and phosphodiesterase-5 inhibitors used together for the treatment of erectile dysfunction induces a major decrease of blood tension and might lead to death (Thadani and Rodgers, 2006)
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