Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration

Figures & data

Figure 1 Transmission electron microscopic image (A) and size distribution (B) of coumarin-6-loaded PLGA NPs.

Note: Scale bars represent 200 nm.

Abbreviation: PLGA NPs, poly(d,l-lactide-co-glycolide acid) nanoparticles.

Figure 2 Transmission electron microscopic image (A) and size distribution (B) of PLGA NPs loaded with TS IIA, Sal B, and PNS.

Note: Scale bars represent 1 μm.

Abbreviations: PLGA NPs, poly(d,l-lactide-co-glycolide acid) nanoparticles; TS IIA, tanshinone IIA; Sal B, salvianolic acid B; PNS, panax notoginsenoside.

Figure 3 In vitro release profiles for PLGA NPs loaded with TS IIA, Sal B, and PNS and compound solution containing these free drugs (n=3 mean ± SD).

Abbreviations: PLGA NPs, poly(d,l-lactide-co-glycolide acid) nanoparticles; TS IIA, tanshinone IIA; Sal B, salvianolic acid B; PNS, panax notoginsenoside; R₁, notoginsenoside R₁; Rg₁, ginsenoside Rg₁; Rb₁, ginsenoside Rb₁; h, hours; SD, standard deviation.

Table 1 Pharmacokinetic parameters of coumarin-6 after RW administration of coumarin-6 nanoparticles and solution in PL

Parameters of coumarin-6	Nanoparticles	Solution
Tmax (h)	0.5	2
Cmax (ng/mL)	201.46	18.46
AUC0–t (ng h/mL)	563.60	119.70

Abbreviations: PL, perilymph; RW, round window; AUC, total area under the perilymph concentration versus time curve from time zero to time infinity; C_max, peak perilymph concentration; T_max, time to reach C_max.

Figure 4 PL concentration versus time curves in guinea pigs after RW administration of coumarin-6 nanoparticles and solution (n=3, mean ± SD).

Abbreviations: PL, perilymph; RW, round window; SD, standard deviation.

Table 2 Pharmacokinetic parameters of TS IIA, Sal B, and PNS after RW administration of compound solution and PLGA NPs loaded with TS IIA, Sal B, and PNS in PL and plasma

Parameters	Tissue	Nanoparticles					Solution
		R1	Rg1	Rb1	Sal B	TS IIA	R1	Rg1	Rb1	Sal B	TS IIA
Tmax (h)	PL	0.5	1	0.5	0.5	0.5	2	3	3	1	1
	Plasma	10	0.5	8	1	2	3	0.16	4	0.03	0.08
Cmax (μg/mL)	PL	965.94	1,383.36	1,692.39	354.84	9.47	67.17	137.84	101.32	683.29	35.69
	Plasma	7.50	5.49	14.70	6.89	3.69	36.33	15.6	14.33	6.41	0.85
AUC0–t (μg h/mL)	PL	1,867.32	3,136.83	4,471.89	581.45	29.98	468.76	1,026.04	628.48	2,385.03	57.97
	Plasma	67.65	42.44	141.58	24.06	28.93	187.05	149.33	172.77	15.58	1.18

Abbreviations: PL, perilymph; RW, round window; TS IIA, tanshinone IIA; Sal B, salvianolic acid B; PNS, panax notoginsenoside; R₁, notoginsenoside R₁; Rg₁, ginsenoside Rg₁; Rb₁, ginsenoside Rb₁; AUC, total area under the perilymph or plasma concentration versus time curve from time zero to time infinity; C_max, peak perilymph or plasma concentration; T_max, time to reach C_max.

Figure 5 PL concentration versus time curves in guinea pigs after RW administration of PLGA NPs loaded with TS IIA, Sal B, and PNS (n=3, mean ± SD).

Abbreviations: PL, perilymph; RW, round window; PLGA NPs, poly(d,l-lactide-co-glycolide acid) nanoparticles; TS IIA, tanshinone IIA; Sal B, salvianolic acid B; PNS, panax notoginsenoside; R₁, notoginsenoside R₁; Rg₁, ginsenoside Rg₁; Rb₁, ginsenoside Rb₁; SD, standard deviation.

Figure 6 PL concentration versus time curves in guinea pigs after RW administration of compound solution of TS IIA, Sal B, and PNS (n=3, mean ± SD).

Abbreviations: PL, perilymph; RW, round window; TS IIA, tanshinone IIA; Sal B, salvianolic acid B; PNS, panax notoginsenoside; R₁, notoginsenoside R₁; Rg₁, ginsenoside Rg₁; Rb₁, ginsenoside Rb₁; SD, standard deviation; h, hours.

Figure 7 Plasma concentration versus time curves in guinea pigs after RW administration of PLGA NPs loaded with TS IIA, Sal B and PNS (n=3, mean ± SD).

Abbreviations: PL, perilymph; RW, round window; PLGA NPs, poly(d,l-lactide-co-glycolide acid) nanoparticles; TS IIA, tanshinone IIA; Sal B, salvianolic acid B; PNS, panax notoginsenoside; R₁, notoginsenoside R₁; Rg₁, ginsenoside Rg₁; Rb₁, ginsenoside Rb₁; SD, standard deviation; h, hours.

Figure 8 Plasma concentration versus time curves in guinea pigs after RW administration of compound solution of TS IIA, Sal B, and PNS (n=3, mean ± SD).

Abbreviations: PL, perilymph; RW, round window; TS IIA, tanshinone IIA; Sal B, salvianolic acid B; PNS, panax notoginsenoside; R₁, notoginsenoside R₁; Rg₁, ginsenoside Rg₁; Rb₁, ginsenoside Rb₁; SD, standard deviation; h, hours.