Glucose-sensing pulmonary delivery of human insulin to the systemic circulation of rats

Figures & data

Figure 1 Con A based AVT particles: Liposomes bearing PEG-sugar conjugates on their external surface are agglomerated by free con A.

Table 1 Pharmacodynamic parameters of the untreated and the treated group during the three glucose excursions

Parameters(mean ± SD)	Excursion 1 (t = 0 ± 90) Control	Excursion 2 (t = 90 ± 195) Treated	Excursion 3 (t = 225 ± 325) Control	Treated	Control	Treated
Cmax (mg dL^–1)	353 ± 46	320 ± 62	459 ± 27	324 ± 48	525 ± 43	273 ± 39
tmax (min)	40	0	120	110	255	250
Cbasal (mg dL^–1)	145 ± 27	145 ± 27	284 ± 37	98 ± 11	240 ± 7	105 ± 32
AUCe (10^3 mg dL^–1 min)	18.5 ± 4	9.4 ± 2.2	10.4 ± 5.3	7.3 ± 1.5	15.5 ± 5	4.6 ± 3.2

Figure 2 Size distributions measured by Fraunhofer Diffraction of con A-linked liposomes before and upon cleavage by free glucose.

Figure 3 Aerodynamic characterization of the agglomerated liposomes by cascade impactor.

Figure 4 Blood glucose concentration over the period of ~6 hrs of the untreated group (n = 3), treated group with lung instillation of the AVT particle containing 1.4 IU/kg (n = 3), and the treated group with lung instillation of the AVT particle containing 1.4 IU/kg followed by hyperglycemic events (n = 4). The asterisk and the double cross indicate significant statistical difference based on two-tailed student’s t-test (p < 0.05, a = 0.05) between the treated group in the presence of hyperglycemic events and the control group and between the two treated groups respectively.

Figure 5 A comparison of the control and the AVT-treated group during the 3 hyperglycemic events. The shaded areas indicate the areas under the curve (AUC_e) for each excursion.

Figure 6 Histological analysis of hematoxylin-eosin stained lung tissue 24 hrs after treatment (original magnification 100X); (A) In saline-treated animals (n = 2), the lung tissue was almost entirely normal, as shown in this view; (B) The con A-treated rats (n = 2) demonstrated extensive pneumonic changes in their lungs. A bronchiole and adjacent alveoli show mixed inflammatory cell infiltrates including neutrophils and lymphocytes, accompanied by alveolar hemorrhage; (C) In liposome-treated animals (n = 2), patchy lymphocytic infiltrates were noted around a bronchiole, blood vessels, and in the interstitium in the left upper lobe of one of the rats receiving the liposomes; (D) In AVT-treated animals (n = 2), alveolar material is focally visible (see arrows) in the lungs, and may represent remnants of the particles (original magnification 100X).