TY - JOUR
T1 - Stable Atropine Loaded Film As a Potential Ocular Delivery System For Treatment Of Myopia
AU - Ji, Muse
AU - Liu, Hongbing
AU - Ma, Shuting
AU - Kong, Jun
AU - Jia, Yannan
AU - Gou, Jingxin
AU - Yin, Tian
AU - He, Haibing
AU - Zhang, Yu
AU - Tang, Xing
N1 - Funding Information:
This work was supported by the National Mega-project for Innovative Drugs [2019ZX09721001], National Key R&D Program of China [2020YFE0201700], Liaoning Revitalization Talents Program [XLYC1907111, XLYC1908031], Liaoning Province Doctoral Start-up Fund Program [2019-BS-226], Liaoning BaiQianWan Talents Program [(2020)78], Career Development Program for Young and Middle-aged Teachers of Shenyang Pharmaceutical University [ZQN2019004] and Dual Service Program of University in Shenyang.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/11
Y1 - 2021/11
N2 - Purpose: The objective of the present study was to prepare stable and high bioavailability ocular atropine loaded films (ATR-films) as potential ocular drug delivery systems for the treatment of myopia. Methods: ATR-films were prepared by the solvent casting method and the physical properties of films were evaluated including thickness, water content, light transparency, disintegration time, and mechanical properties. FT-IR, DSC, XRD, TGA, AFM, and Raman spectroscopy were performed to characterize the film. The stability test was conducted under different conditions, such as high humidity, high temperature, and strong light. The pharmacokinetic study and irritation assessment were conducted in rabbits. The efficacy of ATR-films was evaluated by refraction and ocular biometry in myopia guinea pigs. Result: After optimizing the formulation, the resulting ATR-film was flexible and transparent with lower water content (8.43% ± 1.25). As expected, the ATR-film was stable and hydrolysate was not detected, while the content of hydrolysate in ATR eye drops can reach up to 8.1867% (limit: < 0.2%) in the stability study. The safety assessment both in vitro and in vivo confirmed that the ATR-film was biocompatible. Moreover, the bioavailability (conjunctiva 3.21-fold, cornea 2.87-fold, retina 1.35-fold, sclera 2.05-fold) was greatly improved compared with the ATR eye drops in vivo pharmacokinetic study. The pharmacodynamic study results showed that the ATR-film can slow the progress of form-deprivation myopia (~ 100 ± 0.81D), indicating that it has a certain therapeutic effect on form-deprivation myopia. Conclusion: The ATR-film with good stability and high bioavailability will have great potential for the treatment of myopia.
AB - Purpose: The objective of the present study was to prepare stable and high bioavailability ocular atropine loaded films (ATR-films) as potential ocular drug delivery systems for the treatment of myopia. Methods: ATR-films were prepared by the solvent casting method and the physical properties of films were evaluated including thickness, water content, light transparency, disintegration time, and mechanical properties. FT-IR, DSC, XRD, TGA, AFM, and Raman spectroscopy were performed to characterize the film. The stability test was conducted under different conditions, such as high humidity, high temperature, and strong light. The pharmacokinetic study and irritation assessment were conducted in rabbits. The efficacy of ATR-films was evaluated by refraction and ocular biometry in myopia guinea pigs. Result: After optimizing the formulation, the resulting ATR-film was flexible and transparent with lower water content (8.43% ± 1.25). As expected, the ATR-film was stable and hydrolysate was not detected, while the content of hydrolysate in ATR eye drops can reach up to 8.1867% (limit: < 0.2%) in the stability study. The safety assessment both in vitro and in vivo confirmed that the ATR-film was biocompatible. Moreover, the bioavailability (conjunctiva 3.21-fold, cornea 2.87-fold, retina 1.35-fold, sclera 2.05-fold) was greatly improved compared with the ATR eye drops in vivo pharmacokinetic study. The pharmacodynamic study results showed that the ATR-film can slow the progress of form-deprivation myopia (~ 100 ± 0.81D), indicating that it has a certain therapeutic effect on form-deprivation myopia. Conclusion: The ATR-film with good stability and high bioavailability will have great potential for the treatment of myopia.
KW - Atropine
KW - Fast-dissolve
KW - Form-deprivation
KW - Myopia
KW - Ocular film
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U2 - 10.1007/s11095-021-03135-4
DO - 10.1007/s11095-021-03135-4
M3 - Article
C2 - 34773183
AN - SCOPUS:85118998296
SN - 0724-8741
VL - 38
SP - 1931
EP - 1946
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 11
ER -