*Article* **Multi-Responsive Optimization of Novel pH-Sensitive Hydrogel Beads Based on Basil Seed Mucilage, Alginate, and Magnetic Particles**

**Natwat Srikhao <sup>1</sup> , Korrapat Chirochrapas <sup>1</sup> , Nessaraporn Kwansanei <sup>1</sup> , Pornnapa Kasemsiri 1,\*, Artjima Ounkaew <sup>1</sup> , Manunya Okhawilai 2,3,\*, Chutiwat Likitaporn <sup>4</sup> , Somnuk Theerakulpisut <sup>5</sup> and Hiroshi Uyama <sup>6</sup>**


**Abstract:** Conventional drug delivery systems often cause side effects and gastric degradation. Novel drug delivery systems must be developed to decrease side effects and increase the efficacy of drug delivery. This research aimed to fabricate hydrogel beads for use as a drug delivery system based on basil seed mucilage (BSM), sodium alginate (SA), and magnetic particles (MPs). The Taguchi method and Grey relational analysis were used for the design and optimization of the hydrogel beads. Three factors, including BSM, SA, and MPs at four levels were designed by L-16 orthogonal arrays. BSM was the main factor influencing bead swelling, drug release rate at pH 7.4, and release of antioxidants at pH 1.2 and 7.4. In addition, SA and MPs mainly affected drug loading and drug release rate in acidic medium, respectively. Grey relational analysis indicated that the composition providing optimal overall properties was 0.2 vol% BSM, 0.8 vol% SA, and 2.25 vol% MPs. Based on the findings of this work, BSM/SA/MPs hydrogel beads have the potential to be used as a pH-sensitive alternative material for drug delivery in colon-specific systems.

**Keywords:** hydrogel beads; Taguchi's method; Grey relational analysis; drug delivery system
