A lecithin-based microemulsion of rh-insulin with aprotinin for oral administration: Investigation of hypoglycemic effects in non-diabetic and STZ-induced diabetic rats

Cilek, Ayşe; Çelebi, Nevin; Tırnaksız, Figen; Tay, Aydin

doi:10.1016/j.ijpharm.2005.04.016

Cited by 76 publications

(29 citation statements)

References 31 publications

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“…The optimised dispersion exhibited physical stability for at least six months at 4°C, 25°C and 40°C, although pseudo-ternary phase diagrams prepared during the preparation of the microemulsion clearly indicate the destabilising effect of water [297]. Intra-gastric delivery of 200 IU insulin in this microemulsion lowered blood sugar in diabetic rats to the same level as the s.c. dose (0.3 IU), but dose correction revealed a pharmacological activity (PA) of less than 0.2% [298]. Delivering Macrulin TM to healthy patients via intra-duodenal intubation increased plasma insulin levels and lowered blood sugar [299].…”

Section: Permeation Enhancement From Water-in-oil Systemsmentioning

confidence: 99%

Intestinal permeation enhancers for oral peptide delivery

Maher

Mrsny

Brayden

2016

Advanced Drug Delivery Reviews

288

201

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Publication informationAdvanced Drug Delivery Reviews, (Part B): 277-319 Publisher ElsevierItem record/more information http://hdl.handle.net/10197/7800Publisher's statement þÿ T h i s i s t h e a u t h o r s v e r s i o n o f a w o r k t h a t w a s a c c e p t e d f o r p u b l i c a t i o n i n A d v a n c e d D r u g Delivery Reviews. Changes resulting from the publishing process, such as peer review,

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Section: Permeation Enhancement From Water-in-oil Systemsmentioning

confidence: 99%

Intestinal permeation enhancers for oral peptide delivery

Maher

Mrsny

Brayden

2016

Advanced Drug Delivery Reviews

288

201

View full text Add to dashboard Cite

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“…These microemulsions displayed a 10-fold enhancement in bioavailability compared with a plain insulin solution administered orally to healthy rats [85]. The improved oral bioavailability of the w/o microemulsion system was also shown for a lecithin-based microemulsion of rhinsulin [86]. On the other hand, Kraeling and Ritschel [87] found that the oral pharmacological availability of insulin microemulsions as compared with intravenous insulin in beagle dogs was 2.1%, which further increased to 6.4% with the encapsulation of gelled microemulsions in hard gelatine capsules along with the protease inhibitor aprotinin and coating of the capsules for colonic release [87].…”

Section: Microemulsionsmentioning

confidence: 78%

Oral Delivery of Insulin: Novel Approaches

Elsayed¹

2012

Recent Advances in Novel Drug Carrier Systems

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“…The areas above the serum glucose levels time curves (AAC) were calculated using the linear trapezoidal rule. 13,14) The relative pharmacological availability (PA %) of the intratracheally administered rh-insulin was calculated using the following equation.…”

Section: Induction Of Diabetes In Ratsmentioning

confidence: 99%

Effect of Pulmonary Surfactant and Phospholipid Hexadecanol Tyloxapol on Recombinant Human-Insulin Absorption from Intratracheally Administered Dry Powders in Diabetic Rats

Zheng

Zhang

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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Pulmonary delivery of drugs has been used extensively in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis for many years. 1,2) Recently it is also studied widely for a optional administration route of large molecules drugs because the lung has large surface area, good permeability and high blood flow.3) Several drug delivery carriers have been used in the pulmonary administration of peptides and proteins including insulin. These can be liquid, solid or gaseous excipients, as has been reviewed by Courrier et al. 4) Compared with other carriers, dry powders offer more advantages, including enhanced drug stability, greater accuracy in dosing, breath-actuated delivery, improved patient compliance, and preferred delivery systems for protein and peptide drugs that are susceptible to degradation upon extended storage in aqueous solution.5) However, under normal circumstances, the alveolar-capillary barrier prevents fast absorption of macromolecules into the blood and thus the bioavailability is not high enough to promise effective systemic therapy.6,7) So, efficient pulmonary delivery requires drug powders with some additives (e.g. absorption enhancers), which can increase the amount of macromolecules reaching the blood flow. Various protease inhibitors, surfactants, lipids, polymers and other agents have been tested to improve the systemic availability of macromolecular drugs by pulmonary administration, but most of them were unsatisfactory for effectiveness or safety reasons. 8)Pulmonary surfactant (PS), a complex mixture of 78-90% phospholipids, 5-10% proteins and 4-10% neutral lipids, is synthesized and released by type II alveolar epithelial cells mainly to reduce surface tension at the gas-liquid interface of the lung. Jing et al. 9) proved that artificial pulmonary surfactant had the potential to improve the bioavailability of intratracheally instilled insulin. Our previous studies revealed that PS could enhance the absorption of insulin by lung in normal rats and it might be a possible absorption enhancer.10) However, the development of PS as absorption enhancer is difficult because of its limited content and perishable composition. Meanwhile, previous works in our laboratory showed that phospholipid hexadecanol tyloxapol (PHT), the analogical composition of PS, had similar capacity to promote the absorption of pulmonarily administered recombinant human insulin (rh-insulin) in normal rats (data not published yet). Then, it was speculated that PHT could be a promising absorption enhancer which could be applied to facilitate the pulmonary absorption of insulin.The objective of the present study was to evaluate the in vivo pharmacological activity of PS-or PHT-loaded dry powders for pulmonary delivery of rh-insulin in diabetic rats. Meanwhile, the toxicity of PS and PHT was estimated through a BAL (Bronchoalveolar Lavage) method. ExperimentalMaterials Streptozotocin (STZ) was obtained from Sigma-Aldrich (St. Louis, U.S.A.). Recombinant human ...

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A lecithin-based microemulsion of rh-insulin with aprotinin for oral administration: Investigation of hypoglycemic effects in non-diabetic and STZ-induced diabetic rats

Cited by 76 publications

References 31 publications

Intestinal permeation enhancers for oral peptide delivery

Intestinal permeation enhancers for oral peptide delivery

Oral Delivery of Insulin: Novel Approaches

Effect of Pulmonary Surfactant and Phospholipid Hexadecanol Tyloxapol on Recombinant Human-Insulin Absorption from Intratracheally Administered Dry Powders in Diabetic Rats

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