Magnetic Nanogel Polymer of Bupivacaine for Ankle Block in Rats

Sadigheh Nadri, Lorestan University of Medical sciences and Hormoz Mahmoudvand, Lorestan University of Medical sciences and Ali Eatemadi, Tehran University of Medical sciences (2016) Magnetic Nanogel Polymer of Bupivacaine for Ankle Block in Rats. Journal of Microencapsulation Micro and Nano Carriers. ISSN 0265-2048

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Abstract

Introduction: In an effort of designing an alternative method for local nerve block, we demonstrated the possibility of inducing ankle block in the rat with intravenous (IV) injection of magnetic nanoparticles conjugated bupivacaine and application of a magnet at the ankle. Methods: The anesthetic effect of magnet-directed bupivacaine-associated MNPs (NIPAAM-MAAbupivacaine) was tested in rat using paw withdrawal latencies from thermal stimuli on the hindpaw. Thirteen (13) experimental animals were grouped into two; untreated left hindpaw (control group), and test group with treated right hindpaw. The morphology of the synthesized nanogel was analysed using surface electron micrograph (SEM), chemical characterization using FTIR and NMR, and finally the in vivo drug release using UV spectroscopy. Results: UV Spectroscopy result show that, at 37°C a sharp increase was observed from 24-72h (40- 75%) cumulative drug release at pH 5.3, a steady increase from 21-60% and 20-40% at pH 6.8 and 7.4 respectively. At 43°C a steady increase was observed at the three pH, 37-72%, 20-35% and 10-19% at pH 5.3, 6.8 and 7.4 respectively. It was shown also that drug release at higher pH (6.8 and 7.4) does not become significantly faster when temperature is high, compared to the release at a pH of 5.3. This depicts that the decreasing pH has more impact on the speed of the release of drug than increasing temperature. NMR and FTIR results displayed a comparable chemical structure as expected. The NMR peak displayed high purity of the final product. Morphology using SEM showed that the nanocomposite size is slightly greater than that of the nanogel, and the nanocomposite particles are nearly mono dispersed. Paw withdrawal latency highest peak of 15% was observed for NG/PU/30 at 40hours, and lowest peak for NG/30 at 50hours for the left paw. Group BU0.15 at 30hours shows the highest peak (20%) and NG/30 at 120h shows the lowest peak for the right treated paw, which is significantly difference from the untreated left paw group (P< 0.0001). However, there wasn’t a significant difference amongst NG/30, NG/Pub/15, or NG/Pub/60. JUST ACCEPTED Conclusions: The current study verifies the findings that we can induce ankle block in rat through IV injection administration of NIPAAM-MAA-bupivacaine complexes and the application of magnet at the ankle. We however suggest a lower temperature and pH for optimum release of this nanoanesthetics, there is a probability of translating this mechanism to clinical practice. Keywords: Nanogel; Magnetic nanoparticles; Anesthesia; Ankle block; Bupivacaine

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