Thermosensitive In Situ Gelling Poloxamers/Hyaluronic Acid Gels for Hydrocortisone Ocular Delivery

Abstract

This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye's surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel-water interactions, indicating that HA affects the water-polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain.

Keywords: DSC; hyaluronic acid; hydrocortisone release kinetics; hydrogels; in situ forming drug reservoir; ophthalmic drug delivery; thermosensitive systems.

Figure 1

Fourier transform infrared spectra (FTIR) of raw materials and selected hydrogels (left). Scanning electron microscopy (SEM) micrographs of freeze-dried hydrogels with (right) or without HC (left).

Figure 2

Mechanical spectra of unloaded pol/HA platforms at three different temperatures: 4 °C (A), 25 °C (B) and 37 °C (C).

Figure 3

Elastic and viscous moduli as a function of temperature, at a fixed frequency of 1 Hz for formulations P3/0.1, P3/1 and P4/0.1, unloaded (left) and HC loaded (right). The error bars are omitted for clarity purpose.

Figure 4

Thermograms of (A) P3/0.1; (B) P3/1; (C) P4/0.1.

Figure 5

Swelling ratio of dried gel formulations.

Figure 6

Hydrocortisone release curves from pol/HA gels.