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Research Article

Modification of translationally controlled tumor protein-derived protein transduction domain for improved intranasal delivery of insulin

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Pages 1025-1032 | Received 28 Jan 2018, Accepted 09 Apr 2018, Published online: 24 Apr 2018

Figures & data

Figure 1. (a) Amino acid sequence of l-TCTP-PTD 13 and its analogs. Amino acid modifications in l-TCTP-PTD 13 are underlined. (b) Cellular uptake of FITC-labeled peptides in BEAS-2B cells analyzed by a flow cytometer. (c) Histograms of l-TCTP-PTD 13, l-TCTP-PTD 13M1, and l-TCTP-PTD 13M2. Each bar represents the standard deviation of three independent replicates. The mean fluorescence intensity of FITC-labeled l-TCTP-PTD 13 in BEAS-2B cells was set to 100%. *p < .05 versus FITC-labeled l-TCTP-PTD 13.

Figure 1. (a) Amino acid sequence of l-TCTP-PTD 13 and its analogs. Amino acid modifications in l-TCTP-PTD 13 are underlined. (b) Cellular uptake of FITC-labeled peptides in BEAS-2B cells analyzed by a flow cytometer. (c) Histograms of l-TCTP-PTD 13, l-TCTP-PTD 13M1, and l-TCTP-PTD 13M2. Each bar represents the standard deviation of three independent replicates. The mean fluorescence intensity of FITC-labeled l-TCTP-PTD 13 in BEAS-2B cells was set to 100%. *p < .05 versus FITC-labeled l-TCTP-PTD 13.

Figure 2. (a and b) Plasma insulin concentration in normal rats following intranasal administration of insulin in the presence of 0.1 mM (a) or 0.25 mM (b) TCTP-PTD analogs containing l-amino acids. (c) Plasma insulin concentration following intranasal administration of insulin with 0.25 mM d-TCTP-PTD analogs. Insulin doses were 5 and 1 IU/kg for insulin alone and insulin plus PTD, respectively. Vertical bars indicate means ± SEM (n = 5–7). (d) LDH leakage in nasal fluid of normal rats following intranasal administration of insulin (1 IU/kg) with different PTDs. Sodium taurodeoxycholate (5% w/v) served as a positive control. Each bar represents mean ± SEM (n = 6). *p < .01 versus insulin alone.

Figure 2. (a and b) Plasma insulin concentration in normal rats following intranasal administration of insulin in the presence of 0.1 mM (a) or 0.25 mM (b) TCTP-PTD analogs containing l-amino acids. (c) Plasma insulin concentration following intranasal administration of insulin with 0.25 mM d-TCTP-PTD analogs. Insulin doses were 5 and 1 IU/kg for insulin alone and insulin plus PTD, respectively. Vertical bars indicate means ± SEM (n = 5–7). (d) LDH leakage in nasal fluid of normal rats following intranasal administration of insulin (1 IU/kg) with different PTDs. Sodium taurodeoxycholate (5% w/v) served as a positive control. Each bar represents mean ± SEM (n = 6). *p < .01 versus insulin alone.

Table 1. Pharmacokinetic parameters following intranasal administration of insulin plus TCTP-PTD analogs in normal rats.

Figure 3. Changes in blood glucose levels in rats with alloxan-induced diabetes following intranasal administration of insulin plus l-TCTP-PTD analogs. Insulin doses were 2 and 1 IU/kg for administration by the nasal route and s.c. injection, respectively. Vertical bars indicate means ± SEM (n = 6–8).

Figure 3. Changes in blood glucose levels in rats with alloxan-induced diabetes following intranasal administration of insulin plus l-TCTP-PTD analogs. Insulin doses were 2 and 1 IU/kg for administration by the nasal route and s.c. injection, respectively. Vertical bars indicate means ± SEM (n = 6–8).

Table 2. Pharmacodynamics of insulin in rats with alloxan-induced diabetes.

Figure 4. (a) Body weight of normal mice (n = 6) after daily intraperitoneal injection of l-TCTPPTD 13M2 for 10 days. (b) Biochemical analysis of AST, ALT, BUN, and CRE levels.

Figure 4. (a) Body weight of normal mice (n = 6) after daily intraperitoneal injection of l-TCTPPTD 13M2 for 10 days. (b) Biochemical analysis of AST, ALT, BUN, and CRE levels.
Supplemental material

Supplementary data

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