Molecular Pharmaceutics
Article
caine in solution were presumably the same. It is possible that
the drug in suspension acted as a drug reservoir replenishing
the concentration of free drug on the TM surface as it was
depleted by flux.
sulfate; Susp, suspension; TTX, tetrodotoxin; TMs, tympanic
membranes
REFERENCES
■
We have previously shown, using a similar hydrogel delivery
system, that transtympanic drug delivery results in no
detectable systemic (blood) distribution of the antibiotic
(
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bupivacaine and TTX would also not result in systemic drug
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the anesthetics. This treatment would also obviate the need
for systemic (oral) analgesics and their potential side effects.
The thermosensitive hydrogel was designed to provide
sustained pain relief and enable easy administration. The
hydrogel formulation is a solution under room temperature for
administration through the ear canal like other regular ear
drops; the formulation gels quickly in situ upon contacting the
warm TM. Only a single application is required to maintain
local anesthesia over prolonged periods, which is beneficial
because multidose regimens can cause poor compliance among
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. CONCLUSIONS
A local drug delivery system was developed to provide
sustained pain relief from a single application in patients
with AOM. A commonly used amino-amide anesthetic,
bupivacaine, was successfully delivered across intact TMs, as
was a highly potent site 1 sodium channel blocker anesthetic,
TTX. The chemical permeation enhancers incorporated in the
hydrogel system considerably increased the permeability of
BUP and TTX across the TM.
5
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Randomized, Double-Blind, Multicentre Controlled Trial of Ibupro-
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ASSOCIATED CONTENT
Supporting Information
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AUTHOR INFORMATION
Corresponding Author
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Assessing Ototopical Agents in the Treatment of Pain Associated with
Acute Otitis Media in Children. International Journal of Pediatric
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Notes
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13) Khoo, X.; Simons, E. J.; Chiang, H. H.; Hickey, J. M.;
Sabharwal, V.; Pelton, S. I.; Rosowski, J. J.; Langer, R.; Kohane, D. S.
The authors declare no competing financial interest.
Formulations for Trans-Tympanic Antibiotic Delivery. Biomaterials
2
(
013, 34 (4), 1281−1288.
14) Yang, R.; Sabharwal, V.; Okonkwo, O. S.; Shlykova, N.; Tong,
ACKNOWLEDGMENTS
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R.; Lin, L. Y.; Wang, W.; Guo, S.; Rosowski, J. J.; Pelton, S. I.
Treatment of Otitis Media by Transtympanic Delivery of Antibiotics.
Sci. Transl. Med. 2016, 8 (356), 356ra120.
This work was financially supported by NIHDC015050 to
D.S.K., NIHDC016644 to R.Y., the Trailblazer Research Grant
by the Department of Anesthesia at Boston Children’s
Hospital and the Charles H. Hood Foundation Child Health
Research Award to R.Y., the Jane and Aatos Erkko Foundation,
and the Orion Research Foundation to R.S.
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Ghoroghchian, P.; Hunfeld, N. G. M.; Berde, C. B.; Langer, R.
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ABBREVIATIONS
■
BUP, bupivacaine; BUP-fb, bupivacaine free base; CPEs,
chemical permeation enhancers; LIM, limonene; P407-PBP,
poloxamer 407-polybutylphospoester; SDS, sodium dodecyl
5
68−573.
(17) Adams, H. J.; Blair, M. R. J.; Takman, B. H. The Local
Anesthetic Activity of Saxitoxin Alone and with Vasoconstrictor and
G
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