A sublingual electronic pill is a novel device designed to enhance delivery of drugs/biologics sublingually utilizing low-current electrical stimulation. Our primary aim was to explore safe limits of oral electrical stimulus in animals and conduct a randomized, sham-controlled animal study to quantify benefits of electrical stimulation on sublingual absorption of octreotide (a small peptide) as a first step in the development of this technology.
A system to deliver low-current alternating and direct current stimuli to the oral mucosa of rabbits was constructed, and five groups were studied to determine the significance of sublingual octreotide diffusion in the presence of three different electrical stimulation scenarios: +DC (+4 mA), -DC (-4 mA), and AC (2 mA peak-to-peak, 20 Hz square wave). These were compared to an Oral Baseline Absorption Group (sublingual diffusion in the absence of stimulation) to determine statistical significance of electrical stimulus; and a Subcutaneous Control Group (bolus injection) to discern therapeutic significance.
+DC stimulation (4mA) increased serum concentration 28x with high statistical significance (p-value=0.0008). -DC stimulation (-4mA) increased serum concentration by 19x with borderline significance (p=0.032). AC (20 Hz) stimulus (2mA peak-peak) increased serum concentration by 10x, but was not statistically significant.
The absorption rate of octreotide was also calculated for each group and compared at t=10 minutes and t=30 minutes. The absorption rate of the +DC group was 28x greater than that of Baseline Group and was statistically significant (p=0.0008). The absorption rate of the -DC group was 19x greater than that of the Baseline Group and was statistically significant (p=0.032). The absorption rate of the AC group was 10x greater than the Baseline Group but was not statistically significant (p=0.135).
While none of the sublingual groups reached therapeutically significant serum concentrations, therapeutic levels of sublingually-delivered octreotide could potentially be achieved by extending octreotide exposure and stimulation time, coupled with utilizing sublingual octreotide in higher concentrations. This research was a necessary first step in successful realization of the SEP device.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2012-08-11727 |
| Date | 2012 August 1900 |
| Creators | Bolch, Christina M. |
| Contributors | Criscione, John C. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | thesis, text |
| Format | application/pdf |
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