Microemulsions as Lipid Nanosystems Loaded into Thermoresponsive In Situ Microgels for Local Ocular Delivery of Prednisolone

Rania Hamed; Amani D Abu Kwiak; Yasmeen Al-Adhami; Alaa M Hammad; Rana Obaidat; Osama H Abusara; Rana Abu Huwaij

doi:10.3390/pharmaceutics14091975

Microemulsions as Lipid Nanosystems Loaded into Thermoresponsive In Situ Microgels for Local Ocular Delivery of Prednisolone

Pharmaceutics. 2022 Sep 19;14(9):1975. doi: 10.3390/pharmaceutics14091975.

Authors

Rania Hamed¹, Amani D Abu Kwiak^{1

2}, Yasmeen Al-Adhami¹, Alaa M Hammad¹, Rana Obaidat³, Osama H Abusara¹, Rana Abu Huwaij⁴

Affiliations

¹ Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
² Department of Pharmacy, Faculty of Pharmacy, Zarqa University, Zarqa 13110, Jordan.
³ Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
⁴ Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Al-Salt 19328, Jordan.

Abstract

This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25-0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic^® F127 (F127) or combinations of 12% F127 and 1-10% Kolliphor^®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (-21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37-5.81), surface tension (30.96-38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1-23.9 nm and -1.34 to -10.25 mV, respectively), phase transition temperature (25.3-36 °C), and gelation time (1.44-2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16-24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery.

Keywords: Pluronic® F127; eye irritation; in situ thermoresponsive microgel; kolliphor® P188 (F68); local ocular delivery; microemulsion; mixed polymeric micelles; mucoadhesion; prednisolone; rheological properties.

Grants and funding

This work was partially funded by the Deanship of Research at Al-Zaytoonah University of Jordan, Amman, Jordan (Fund No. 32/11/2020-2021). In addition, the DSC analysis was funded by the Deanship of Research at Jordan University of Science and Technology (Fund No. 404/2017).