Development of triblock polymersomes for catalase delivery based on quality by design environment

Abstract

Catalase is an antioxidant enzyme with potential application in photoprotection, skin aging, and skin disorders as vitiligo. However, as a large and hydrophilic molecule, catalase topical application is hampered by poor skin penetration. In this sense, nanostructured drug delivery systems such as polymersomes (polymeric vesicles) can significantly promote the enzyme access to skin. Since the concept of designing quality in early stages of biotechnological products development is a regulatory demand over the world, in this study, we employed Quality by Design (QbD) principles to design catalase-loaded polymersomes for topical products. QbD and Design of Experiments (DoE) approaches were used to investigate the impact of stirring speed (SS =750 and 1500 rpm), stirring time (ST = 24 and 48 h), and concentration of catalase (CAT = 0.48 and 0.24 mg/mL) in pharmaceutical development critical quality attributes of PEO₅PPO₆₈PEO₅ polymersomes for topical application. The design space counterplot of hydrodynamic diameter (200  ≤ HD ≤ 400), encapsulation efficiency (2≤ %EE ≤ 5), polydispersity index (0.1 ≤ PDI ≤ 0.3), as a function of ST and CAT indicated that polymersomes with optimized characteristics could be developed with 0.24 ≥ CAT ≤ 0.40; 40 ≥ ST ≤ 48 and SS= 800 rpm. Encapsulation efficiency (%EE) was determined directly by size exclusion chromatography purification of the polymersomes, and the highest value was %EE = 4.72 ± 0.07 %, nonetheless catalase as an enzyme is effective at very low concentrations. The results point out time and cost-saving strategies that could serve as an initial step to develop a robust industrial process for the production of catalase-loaded topical polymersomes.

Graphical Abstract

KEYWORDS:

• Pluronic L121
• biopharmaceutical
• quality by design
• catalase
• transdermal delivery

Acknowledgments

Additionally, the authors would like to thank Pensabio® and the Brazilian Nanotechnology National Laboratory – LNNano for NTA and Cryo-Tem analysis, respectively.

Additional information

Funding

The authors acknowledge the National Council For Scientific and Technological Development (CNPq Fellowship # 301832/2017-0) and the São Paulo Research Foundation (FAPESP, processes 2016/03887-4 and 2016/22065-5).