In Vitro Evaluation of Kaempferol-Loaded Hydrogel as pH-Sensitive Drug Delivery Systems

Abstract

The purpose of this study was to prepare and evaluate kaempferol-loaded carbopol polymer (acrylic acid) hydrogel, investigate its antioxidant activity in vitro, and compare the effects on drug release under different pH conditions. Drug release studies were conducted in three different pH media (pH 3.4, 5.4, and 7.4). The kaempferol-loaded hydrogel was prepared by using carbopol 934 as the hydrogel matrix. The morphology and viscosity of the preparation were tested to understand the fluidity of the hydrogel. The antioxidant activity of the preparation was studied by scavenging hydrogen peroxide and 2,2-diphenyl-1-picrilhidrazil (DPPH) radicals in vitro and inhibiting the production of malondialdehyde in mouse tissues. The results showed that kaempferol and its preparations had high antioxidant activity. In vitro release studies showed that the drug release at pH 3.4, 5.4, and 7.4 was 27.32 ± 3.49%, 70.89 ± 8.91%, and 87.9 ± 10.13%, respectively. Kaempferol-loaded carbopol hydrogel displayed greater swelling and drug release at higher pH values (pH 7.4).

Keywords: antioxidation; carbopol 934; different pH; drug release; kaempferol.

Figure 1

Preparation process of KAE-GEL.

Figure 2

In vitro diffusion study of KAE-GEL through dialysis membrane (MW:8000–14,000) at 37 °C.

Figure 3

(A) Chemical and structural analysis of KAE. (B) Formation of KAE-GEL.

Figure 4

Free radical scavenging rate of KAE and KAE-GEL on H₂O₂ and DPPH. (A) Antioxidant activities of different concentrations KAE on H₂O₂. (B) Antioxidant activities of 0.1 mg/mL KAE and KAE-GEL on H₂O₂. (C) DPPH radical scavenging mechanism. (D) Different concentrations KAE express the scavenging ability on DPPH free radical. (E) 0.1 mg/mL KAE and KAE-GEL express the scavenging ability on DPPH free radical. This difference is statistically significant, p *** < 0.001.

Figure 4

Free radical scavenging rate of KAE and KAE-GEL on H₂O₂ and DPPH. (A) Antioxidant activities of different concentrations KAE on H₂O₂. (B) Antioxidant activities of 0.1 mg/mL KAE and KAE-GEL on H₂O₂. (C) DPPH radical scavenging mechanism. (D) Different concentrations KAE express the scavenging ability on DPPH free radical. (E) 0.1 mg/mL KAE and KAE-GEL express the scavenging ability on DPPH free radical. This difference is statistically significant, p *** < 0.001.

Figure 5

MDA generation and detection method. (A) MDA production process. (B) Thiobarbituric acid assay.

Figure 6

KAE and KAE-GEL inhibited the production of MDA from the tissues of mouse ex vivo. (A) Color shows the production of MDA in various tissues. A represents negative control group, A₀ represents positive control group, and A_1-3 represents KAE, BLK-GEL, and KAE-GEL. (B) Inhibitory rate of 0.1 mg/mL KAE and KAE-GEL on MDA production in tissues.

Figure 7

(A) Viscosity of hydrogel and final cumulative permeation rate at different pH values. (B) In vitro diffusion study of KAE-GEL through dialysis membrane (MW: 8000–14,000) at different pH values at 37 °C.