Abstract
Brucine (BRU), an active constituent of Strychnos nux-vomica L., is one of the potential agents to control subside swelling in arthritis. However, its hydrophobic nature, poor permeation, shorter half-life, narrow therapeutic window, and higher toxicity impede its clinical applications. Hence, this investigation was aimed to develop and evaluate novel BRU loaded β-cyclodextrin (β-CD) nanosponges (BRUNs) hydrogel consisting rosemary essential oil (RO), which have been tailored for delayed release, enhanced skin permeation, and reduced irritation, while retaining anti-oxidant and anti-inflammatory activities of this bioactive. Firstly, BRUNs were fabricated by melt technique and characterized appropriately. BRUNs6 demonstrated two fold enhancement in BRU solubility (441.692 ± 38.674) with minimum particle size (322.966 ± 54.456) having good PDI (0.571 ± 0.091) and zeta potential (−14.633 ± 6.357). In vitro release results demonstrated delayed release of BRU from BRUNs6 (67 ± 4.25%) over 24 h through molecular diffusion mechanism. Further, preserved anti-inflammatory (53.343 ± 0.191%) and antioxidant potential (60.269 ± 0.073%) of bioactive was observed in BRUNs6. Hence, this Ns batch was engrossed with Carbopol®934 hydrogel with RO and characterized. In vitro (release and anti-inflammatory activity), ex-vivo (skin permeability) and in vivo (carrageenan-induced inflammation) assays along with irritation study were conducted for fabricated hydrogels. Results revealed that in vitro release of BRU was further delayed from Ns hydrogel with RO (56.45 ± 3.01%) following Fickian mechanism. Considerable enhancement in skin permeability (60.221 ± 0.322 µg/cm2/h) and preservation of anti-inflammatory activity (94.736 ± 2.002%) was also observed in BRUNs6 hydrogel containing RO. The irritation of BRU was found reduced (half) after its entrapped in Ns. Further, as a proof of concept, BRUNs6 hydrogel with RO effectively reduced (75.757 ± 0.944%) carrageenan-induced inflammation in rat model in comparison to pure BRU (54.914 ± 1.081%). Hence, BRUNs hydrogel with RO can be considered as a promising alternative for dermal delivery of BRU in arthritis.
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Acknowledgements
V.K. acknowledges funding by ICMR (Indian Council of Medical Research), New Delhi in the context of a senior research fellowship (Grant Number 45/55/2020/Nano/BMS). V.K. and R.R. acknowledge funding under a minor research project award by Guru Jambheshwar University of Science and Technology, Hisar. The authors acknowledge support from the Department of Pharmaceutical Sciences for performing particle size as well as continued key support from the Animal facility house. Grateful to DST, New Delhi for financial support sanctioned to GJUS&T, Hisar under PURSE Program [SR/PURSE/Phase2/40(G)]. The lyophilization with de-freezer and texture analysis facilities were provided by the Department of Food Technology. PXRD and rheology data reported in the present investigation were obtained from the Department of Physics and Central Instrumental Laboratory, respectively, Guru Jambheshwar University of Science and Technology, Hisar.
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Kadian, V., Rao, R. Enhancing anti-inflammatory effect of brucine nanohydrogel using rosemary oil: a promising strategy for dermal delivery in arthritic inflammation. 3 Biotech 14, 157 (2024). https://doi.org/10.1007/s13205-024-03997-6
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DOI: https://doi.org/10.1007/s13205-024-03997-6