DS-1, a Modified Quillaja Saponin, Enhances Ocular and Nasal Absorption of Insulin

Pillion, Dennis J.; Recchia, Joanne; Wang, Ping; Marciani, Dante J.; Kensil, Charlotte R.

doi:10.1002/jps.2600841104

Cited by 31 publications

(23 citation statements)

References 13 publications

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“…The results from this experiment agree with previous studies [1][2][3][4][5][6][7][8][9][10] in that the systemic absorption of insulin through the eye is facilitated by the surfactant in the formulations. However, the amount of enhancer (20 µg) is much less than in previous studies that required at least 250 µg of enhancer per dose of eyedrop solution.…”

Section: Discussionsupporting

confidence: 94%

“…The pharmaceutical aspects of these eyedrops, such as the absorption site for insulin, 1 the role of absorption enhancers, [1][2][3][4][5][6][7][8][9][10] and the correlation between its pharmacokinetics and pharmacodynamics, 1,10 have been well established. The latter allows scientists to easily quantitate the release of insulin by monitoring the changes in blood glucose levels.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Brij-78 on Systemic Delivery of Insulin from an Ocular Device

Lee

Simamora

Yalkowsky

1997

Journal of Pharmaceutical Sciences

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An ocular insert is developed for the controlled systemic delivery of insulin. Commercially available Gelfoam absorbable gelatin sponge, USP, is used in the fabrication of the ocular insert in the form of a matrix system. Two eyedrop formulations and 13 eye device formulations were evaluated. The efficacy of insulin ocular delivery was quantitated by monitoring the changes in its pharmacological response (i.e., blood glucose lowering). The in vivo results from devices containing 0.5 or 1.0 mg of insulin with 20 micrograms of polyoxyethylene-20-stearyl ether (Brij-78) give a substantial improvement in insulin activity and a significant prolongation in its duration compared with the eyedrops. In addition, the mean blood glucose concentration returns to nearly normal levels within 60 min after the removal of the device. Overall, the application of the Gelfoam device makes it feasible to obtain a prolonged systemic delivery of insulin within the desired therapeutic levels without the risk of hypoglycemia.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Effect of Brij-78 on Systemic Delivery of Insulin from an Ocular Device

Lee

Simamora

Yalkowsky

1997

Journal of Pharmaceutical Sciences

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“…Other routes of administration have been developed such as nasal, 1-10 rectal, [11][12][13][14][15] pulmonary, 16,17 and ocular routes. 10,[18][19][20] However, insulin is poorly absorbed by these mucosae, and the addition of absorption enhancers such as surfactants, 2 bile salts, 3,4 phospholipids, 7 sodium tauro-24, 25-dihydrofusidate, 5,6 and cyclodextrins 8,15 have been proposed to elicit a biological effect. However, among all alternative routes for the administration of insulin, the oral route is the most convenient and physiological because insulin undergoes a first hepatic bypass, thus warranting a primary effect by inhibiting hepatic glucose output.…”

Section: Introductionmentioning

confidence: 99%

Poly(alkyl cyanoacrylate) Nanospheres for Oral Administration of Insulin

Damgé¹,

Vranckx

Balschmidt

et al. 1997

Journal of Pharmaceutical Sciences

150

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Poly(alkyl cyanoacrylate) nanocapsules have been successfully used for oral administration of insulin in diabetic rats. This work reports a suitable formulation for insulin-loaded nanospheres composed of full polymeric structures formed by polymerization of isobutyl cyanoacrylate (IBCA) in an acidic medium, insulin (15 U/mL) being added to the polymerization medium 60 min after the onset of polymerization. These nanospheres (MW 364) displayed a mean size of 145 nm and an association rate of 1 U of insulin/mg of polymer. They protected insulin from the degradation by proteolytic enzymes in vitro, especially when they were dispersed in an oily medium (Miglyol 812) containing surfactive agents (Poloxamer 188 and deoxycholic acid). When dispersed in the same medium, insulin-loaded nanospheres (100 U/kg of body weight), administered perorally in streptozotocin-induced diabetic rats, provoked a 50% decrease of fasted glycemia from the second hour up to 10-13 days. This effect was shorter (2 days) or absent when nanospheres were dispersed in water with surfactive agents or not. Using 14C-labeled nanospheres loaded with [125I]insulin, it was found that nanospheres increased the uptake of [125I]insulin or its metabolites in the gastrointestinal tract, blood, and liver while the excretion was delayed when compared to [125I]insulin nonassociated to nanospheres; in addition, 14C- and 125I-radioactivities disappeared progressively as a function of time, parallel to the biological effect. Thus insulin-loaded nanospheres can be considered as a convenient delivery system for oral insulin at the prerequisite that they were dispersed in an oily phase containing surfactants.

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“…Generally an absorption enhancer is required for the systemic absorption of insulin delivered by the ocular route. [97][98][99][100][101][102][103][104][105][106][107][108][109][110][111] Lee and coworkers 96 showed that the device could provide a uniform blood glucose reduction over 8 h with the aid of Brij-78 as an absorption enhancer. Furthermore, this group also showed that similar results could be obtained from enhancer-free devices to which acetic acid had been added and removed by evaporation.…”

Section: A Cyclosporine-loaded Discoid Devicementioning

confidence: 99%