Design of acid-responsive polymeric nanoparticles for 7,3′,4′-trihydroxyisoflavone topical administration

Figures & data

Figure 1 The chemical structure of 734THIF.

Abbreviation: 734THIF, 7,3′,4′-trihydroxyisoflavone.

Table 1 Composition of 734THIF polymeric nanoparticle systems (734N) and blank EE–PVA nanoparticle (blank-N)

Ratio	734THIF (mg)	EE100/alcohol (mg/mL)	PVA/H2O (mg/mL)
1:8:8	20	160/10	160/40
1:4:4	20	80/10	80/40
1:2:2	20	40/10	40/40
Blank-N	–	160/10	160/40

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; EE, eudragit E100; PVA, polyvinyl alcohol.

Figure 2 The HPLC chromatogram of 734THIF.

Abbreviations: HPLC, high-performance liquid chromatography; 734THIF, 7,3′,4′-trihydroxyisoflavone.

Table 2 The drug loading efficiency, encapsulation efficiency, particle size, and PI of 734THIF polymeric nanoparticle systems

Ratio	Drug loading (%)	Encapsulation efficiency (%)	Particle size (nm)	PI
1:8:8	83.45±2.33	98.10±0.84	57.53±2.49*	0.45±0.01*
1:4:4	57.23±7.37	94.05±1.06	106.73±3.21*	0.80±0.11
1:2:2	51.57±1.73	88.50±1.77	167.20±24.87*	0.83±0.12
734THIF			4,849.33±256.86	>1.0

Notes: Values are mean ± SD (n=3).

* P<0.05: statistically significant difference compared with 734THIF.

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; PI, polydispersity index; SD, standard deviation.

Figure 3 Particle size distribution and morphology of 734THIF nanoparticle formulations.

Notes: Particle size distribution of (A) raw 734THIF, (B) 734THIF:EE:PVA (1:2:2), (C) 734THIF:EE:PVA (1:4:4), (D) 734THIF:EE:PVA (1:8:8). (E) Morphology of 734THIF:EE:PVA (1:8:8) by TEM.

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; PVA, polyvinyl alcohol; EE, eudragit E100; TEM, transmission electron microscopy; 734N, 734THIF nanoparticles.

Figure 4 Crystalline-to-amorphous transformation of 734THIF nanoparticle formulation, as demonstrated by (A) powder XRD and (B) DSC.

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; XRD, X-ray diffractometry; DSC, differential scanning calorimetry.

Figure 5 Intermolecular hydrogen-bond formation between EE–PVA polymer and 734THIF, as demonstrated by (A) FTIR and (B) ¹H-NMR spectra.

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; EE, eudragit E100; PVA, polyvinyl alcohol; FTIR, Fourier transform infrared; ¹H-NMR, ¹H-nuclear magnetic resonance; ppm, parts per million.

Figure 6 (A) The cell viability of 734THIF nanoparticle formulation. (B) Photographs of 734N dispersed in various pH buffer solutions. The solubility of 734THIF (C) and 734N (D) in 0.2 M KH₂PO₄ buffer solution at various pH.

Note: *P<0.05 was statistically significant difference compared with 734THIF.

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; 734N, 734THIF nanoparticles.

Figure 7 The surface morphology of lyophilized powder 734THIF (A) and 734THIF nanoparticle formulation (B), as shown by SEM.

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; SEM, scanning electron microscopy.

Figure 8 The contents of 734THIF delivered from raw 734THIF and 734N to different skin layers: stratum corneum (A), epidermis (B), and dermis (C).

Notes: Values are mean ± SD (n=5). *P<0.05: statistically significant difference compared with raw 734THIF.

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; h, hours; SD, standard deviation; 734N, 734THIF nanoparticles.

Table 3 The concentration of raw 734THIF and 734 nanoparticle formulation required to scavenge 50% of DPPH free radicals (SC₅₀)

Sample	SC50 (μg/mL)
734THIF in H2O (734H)	NE
734THIF in DMSO (734D)	12.09±1.65
734THIF nanoparticles in H2O	14.77±0.58

Notes: Values are mean ± SD (n=3).

Abbreviations: 734THIF, 7,3′,4′-trihydroxyisoflavone; DPPH, 2,2-diphenyl-1-picrylhydrazyl; SC₅₀, 50% of scavenging activity; DMSO, dimethyl sulfoxide; NE, no effect; SD, standard deviation.

Figure 9 The DPPH radical scavenging activity of raw 734THIF suspended in deionized water (734H) and DMSO (734D), and 734THIF nanoparticle formulation suspended in deionized water (734N).

Notes: Values are mean ± SD (n=3). *P<0.05: statistically significant difference compared with 734H.

Abbreviations: DPPH, 2,2-diphenyl-1-picrylhydrazyl; 734THIF, 7,3′,4′-trihydroxy-isoflavone; DMSO, dimethyl sulfoxide; SD, standard deviation.