This
paper presents the synthesis of highly biocompatible and biodegradable
poly(lactide-co-glycolide) (PLGA) microchamber arrays
sensitive to low-intensity therapeutic ultrasound (1 MHz, 1–2
W, 1 min). A reliable method was elaborated that allowed the microchambers
to be uniformly filled with epinephrine hydrochloride (EH), with the
possibility of varying the cargo amount. The maximum load of EH was
4.5 μg per array of 5 mm × 5 mm (about 24 pg of EH per
single microchamber). A gradual, spontaneous drug release was observed
to start on the first day, which is especially important in the treatment
of acute patients. Ultrasound triggered a sudden substantial release
of EH from the films. In vivo real-time studies using a laser speckle
contrast imaging system demonstrated changes in the hemodynamic parameters
as a consequence of EH release under ultrasound exposure. We recorded
a decrease in blood flow as a vascular response to EH release from
a PLGA microchamber array implanted subcutaneously in a mouse. This
response was immediate and delayed (1 and 2 days after the implantation
of the array). The PLGA microchamber array is a new, promising drug
depot implantable system that is sensitive to external stimuli.
Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn’t cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency.
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