Attenuation of celecoxib cardiac toxicity using Poly(δ-decalactone) based nanoemulsion via oral route.

Autor: Maru S; School of Pharmacy and Technology Management, SVKM's NMIMS, Babulde, Banks of Tapi River, Mumbai-Agra Road, Shirpur, Maharashtra 425405, India., Verma J; Pharmaceutical Sciences Laboratory Faculty of Science and Engineering Åbo Akademi University 20520 Turku, Finland. Electronic address: jyoti.verma@abo.fi., Wilen CE; Laboratory of Molecular Science and Engineering, Åbo Akademi University, Aurum, Henrikinkatu 2, 20500 Turku, Finland. Electronic address: carl-eric.wilen@abo.fi., Rosenholm JM; Pharmaceutical Sciences Laboratory Faculty of Science and Engineering Åbo Akademi University 20520 Turku, Finland. Electronic address: Jessica.rosenholm@abo.fi., Bansal KK; Pharmaceutical Sciences Laboratory Faculty of Science and Engineering Åbo Akademi University 20520 Turku, Finland; Laboratory of Molecular Science and Engineering, Åbo Akademi University, Aurum, Henrikinkatu 2, 20500 Turku, Finland. Electronic address: kuldeep.bansal@abo.fi.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2023 Nov 01; Vol. 190, pp. 106585. Date of Electronic Publication: 2023 Sep 16.
DOI: 10.1016/j.ejps.2023.106585
Abstrakt: Celecoxib (CLX), a poorly soluble anti-inflammatory drug, requires administration in higher concentrations to produce therapeutic effects, oftentimes resulting in cardiac toxicity. Therefore, in this study, we employed a nanoemulsion technology to improve the solubility of CLX using poly(δ-decalactone) (PDL) polymer as an oil and mPEG-b-PDL as a surfactant. The nanoemulsion (NE) was successfully prepared via the nanoprecipitation method. In vitro characterization was performed for size, drug release, and stability. In vivo studies were performed to establish anti-inflammatory activity, CLX induced cardiac toxicity, and pharmacokinetic profile of NE, post-oral administration. The globular size of less than 100 nm was obtained in NE with high CLX loading. The in vitro drug release studies suggested ∼90% of CLX release from NE within 96 h. A significant anti-inflammatory activity with lowered cardiac marker values was observed for CLX NE compared to a marketed drug formulation. The pharmacokinetic study revealed that the mean retention time of CLX was significantly increased with NE in contrast to the marketed formulation, suggesting the advantage of administering CLX in the form of NE owing to the higher solubility and sustained release pattern. The long-term storage stability study reveals that NE does not show significant changes in terms of size with only a slight decrement in CLX content was observed after 24 months. The obtained results indicate that CLX bioavailability has been considerably improved without being toxic to the heart with the aid of NE and advocate the use of PDL NE for developing oral formulations for poorly soluble drugs.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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