Design and Development of Low- and Medium-Viscosity Alginate Beads Loaded with Pluronic® F-127 Nanomicelles

Abstract

The anionic polymer sodium alginate, a linear copolymer of guluronic and mannuronic acids, is primarily present in brown algae. Copolymers are used in the sodium alginate preparation process to confer on the material strength and flexibility. Micelles and other polymeric nanoparticles are frequently made using the triblock copolymer Pluronic^® F-127. The purpose of the present study is to determine the effect of sodium alginate's viscosity (low and medium) and the presence of Pluronic^® F-127 micelles on the swelling behavior of the prepared pure beads and those loaded with Pluronic^® F-127 micelles. The Pluronic^® F-127 nanomicelles have a size of 120 nm. The swelling studies were carried out at pH = 1.2 (simulated gastric fluid-SGF) for two hours and at pH = 6.8 (simulated intestinal fluid-SIF) for four more hours. The swelling of both low- and medium-viscosity alginate beads was minor at pH = 1.2, irrespective of the use of Pluronic^® F-127 nanomicelles. At pH = 6.8, without Pluronic^® F-127, the beads showed an enhanced swelling ratio for the first four hours, which was even higher in the medium-viscosity alginate beads. With the addition of Pluronic^® F-127, the beads were dissolved in the first and second hour, in the case of the low- and medium-alginate's viscosity, respectively. In other words, the behavior of the mixed hydrogels was the same during the swelling experiments. Therefore, the presence of Pluronic^® F-127 nanomicelles and medium-viscosity sodium alginate leads to a higher swelling ratio. A model drug, acetyl salicylic acid (ASA), was also encapsulated in the mixed beads and ASA's release studies were performed. In conclusion, the prepared systems, which are well characterized, show potential as delivery platforms for the oral delivery of active pharmaceutical ingredients and biopharmaceuticals.

Keywords: Pluronic® F-127; acetyl salicylic acid; alginate beads; crosslinking; hydrogels; micelles; swelling studies; viscosity.

Scheme 1

Schematic representation of (A) Pluronic^® F127 micelles, (B) network of alginate beads, (C) the formation of alginate beads, (D) Pluronic^® F127 micelles loaded with ASA, and (E) alginate beads encapsulated with Pluronic^® F127 micelles loaded with ASA.

Figure 1

TGA thermograms of the prepared alginate beads.

Figure 2

The hydrogel beads after the drying process for 24 h at 80 °C (left) and after their formation in the CaCl₂ 0.1 M solution (right).

Figure 3

Swelling profiles of dry low-velocity (LV) and medium-viscosity (MV) alginate beads with and without Pluronic at pH 1.2 for the first two hours and at pH 6.8 for the next four hours.

Figure 4

SEM micrographs (scale bar = 20 μm (×4256)) of (a) LV alginate beads, (b) LV alginate beads with Pluronic^® F-127, (c) MV alginate beads, and (d) MV alginate beads with Pluronic^® F-127. Dry samples were observed after sputter coating.

Figure 5

In vitro drug release (%) vs. time (min) for the two different formulations (low- and medium-viscosity alginate beads with Pluronic^® F-127) at pH 1.2 (0–120 min) and at pH 6.8 (120–180 min). The results denote the mean value (n = 3).