Objective  To develop an oxybutynin nanotransdermal formulation with high skin permeability based on cubsomes carrier.

Methods  The oxybutynin loaded cubsomes (OXY-CS) was prepared by ultrasonic method. Using particle size, polydispersity index and encapsulation efficiency as evaluation indexes, stirring temperature, stirring time, stirring speed, ultrasound time, ultrasound power, glycerol monooleate/poloxamer 407 ratio (GMO/F127), carrier (GMO+F127)/drug ratio and drug concentration were optimized. The effects of drug concentration, permeation promoter and gel matrix type on skin permeability were investigated using cumulative permeation and skin retention as evaluation indicators.

Results  The prepared OXY-CS had small particle size and high encapsulation efficiency at stirring temperature of 50°C, stirring time of 30 min, stirring speed of 1 000 r/min, ultrasound time of 10 min, ultrasound power of 100 W, GMO/F127 ratio of 2 ∶ 1, carrier/drug ratio of 3 ∶ 1 and drug concentration of 1%, respectively. OXY-CS had high cumulative penetration and skin retention at concentration ≥ 3%. The addition of a permeation promoter to OXY-CS did not increase the cumulative penetration of the drug. The skin permeability of oxybutynin cubsomes gel made with carbomer was significantly better than those of other gel matrices.

Conclusion  In this study, oxybutynin is made into a topical cubsomes gel, which is expected to reduce the incidence of adverse effects associated with oral administration.

1.Jirschele K, Sand PK. Oxybutynin: past, present, and future[J]. Int Urogynecol, 2013, 24(4): 595-604. DOI: 10.1007/s00192-012-1915-8.

2.Vozmediano-chicharro R, Hernández PB, Madurga-patuel B. Insights into the management of overactive bladder with transdermal oxybutynin: a practical review[J]. Res Rep Urol, 2020, 12: 321-330. DOI: 10.2147/RRU.S266400.

3.王雪, 周斌, 王浩, 等. 盐酸奥昔布宁制剂品种开发 [J]. 世界临床药物, 2014, 35(1): 54-59. [Wang X, Zhou B, Wang H, et al. Development of oxybutynin hydrocholoride formulations[J]. Word Clinical Drugs, 2014, 35(1): 54-59.] DOI: 10.13683/j.wph.2014.01.016.

4.Lucente VR, Staskin DR, De E. Development of oxybutynin chloride topical gel for overactive bladder[J]. Open Access J Urol, 2011, 4: 3: 35-42. DOI: 10.2147/OAJU.S17046.

5.Bender J, Ericson MB, Merclin N, et al. Lipid cubic phases for improved topical drug delivery in photodynamic therapy[J]. J Control Release, 2005, 106(3): 350-60. DOI: 10.1016/j.jconrel.2005.05.010.

6.Zeng LJ, Tao C, Liu ZH, et al. Preparation and evaluation of cubic nanoparticles for improved transdermal delivery of propranolol hydrochloride[J]. AAPS PharmSciTech, 2020, 21: 266. DOI: 10.1208/s12249-020-01809-7.

7.Azmi IDM, Moghimi SM, Yaghmur A. Cubosomes and hexosomes as versatile platforms for drug delivery[J]. Ther Deliv, 2015, 6(12): 347-364. DOI: 10.4155/tde.15.81.

8.Li JC, Zhu N, Zhu JX, et al. Self-assembled cubic liquid crystalline nanoparticles for transdermal delivery of paeonol[J]. Med Sci Monit, 2015, 21: 3298-3310. DOI: 10.12659/msm.894484.

9.中国药典2020年版. 二部[S]. 2020: 1311.

10.李泽荣,吴赵莉,乔文梅,等. 枸橼酸西地那非纳米结构脂质载体的制备及体外释放研究[J]. 药物流行病学杂志, 2023, 32(7): 774-779. [Li ZR, Wu ZL, Qiao WM, et al. Preparation and in vitro release of sildenafil citrate loaded nanostructured lipid carrier[J]. Chinese Journal of Pharmacoepidemiology, 2023, 32(7): 774-779.] DOI: 10.19960/j.issn.1005-0698.202307007.

11.曾令军,胡晓木,张灵娜,等. 盐酸普萘洛尔立方液晶凝胶的皮肤渗透性及安全性评价[J]. 中国药师, 2022, 25(5): 806-811. [Zeng LJ, Hu XM, Zhang LN, et al. Study on the percutaneous permeability and safety of propranolol hydrochloride cubosomes gel[J]. China Pharmacist, 2022, 25(5): 806-811.] DOI: 10.19962/j.cnki.issn1008-049.2022.05.009.

12.喻海林, 何文,郭咸希. 脂质体及脂质体凝胶对尼美舒利透皮吸收的比较研究[J]. 中国药师, 2022, 25(1): 59-63. [Yu HL, He W, Guo XX. Comparative study of liposomes and liposomes-in-hydrogel for transdermal absorption of nimesulide[J]. China Pharmacist, 2022, 25(1): 59-63.] DOI: 10.19962/j.cnki.issn1008-049.2022.01.010.

13.中国药典2020年版. 四部[S]. 2020: 457.

14.Davila GW. Transdermal oxybutynin: a new treatment for overactive bladder[J]. Expert Opin Pharmacother, 2003, 4(12): 2315-2324. DOI: 10.1517/14656566.4.12.2315.

15.Staskin DR, Salvatore S. Oxybutynin topical and transdermal formulations: an update[J]. Drugs Today (Barc), 2010, 46(6): 417-425. DOI: 10.1358/dot.2010.46.6.1487750.

16.王志宁,郑利强. 类脂立方液晶作为药物载体的研究 [J]. 化学进展, 2005, 17(3): 417-422. [Wang ZN, Zheng LQ. Progress in cubic phase of lipid liquid crystal as drug delivery system[J]. Progress in Chemistry, 2005, 17(3): 417-422.] DOI: 10.3321/j.issn:1005-281X.2005.03.007.