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Insulin microcrystal suspension as a long-acting formulation for pulmonary delivery.
Eur J Pharm Sci. 2004 Jun; 22(2-3):107-16.EJ

Abstract

Pulmonary delivery provides the most promising non-parenteral route of insulin administration. Insulin was used as a model protein to demonstrate the feasibility of using protein crystals for the pulmonary delivery of a sustained-release protein drug formulation. Insulin microcrystals with a mean diameter of 3 microm were prepared using a seed zone method. The yield of crystallization was very high (95.8 +/- 0.97%), and the microcrystals were recovered with high efficiency (>98%) by centrifugation. Morphological examination using scanning electron microphotography showed the microcrystals to be of a homogeneous rhombohedral shape, with some rhombus forms, without aggregates. After the administration of 32 U/kg of the microcrystal suspension to STZ-induced diabetic SD rats by intratracheal instillation, the blood glucose levels were reduced and hypoglycemia was prolonged over 13 h, as compared to the insulin solution. The percent minimum reductions of the blood glucose concentration (% MRBG) produced by the microcrystal suspension and insulin solution reached 36.5 and 37.2%, respectively, of the initial level, and the percent total reductions in blood glucose (% TRBG(13 h)) were 34.4 and 25.0%, respectively. In the case of inhalation using a sieve-type ultrasonic nebulizer, the % MRBG produced by the microcrystal suspension and insulin solution were 21.7 and 26.3%, respectively, of the initial level, and the % TRBG(13 h) were 66.7 and 58.4%, respectively. However, the hypoglycemic effects of the microcrystal suspension were prolonged over 7 h, which compares favorably with the insulin solution (P<0.5 by unpaired t-test). These results could be attributed to the sustained-release of insulin from the microcrystals, which were deposited widely throughout the entire lung.

Authors+Show Affiliations

Kwon JH
Graduate School of Life Sciences and Biotechnology, Korea University, 1-5 Anam-dong, Sungbuk-ku, Seoul 136-701, Republic of Korea.
Lee BH
No affiliation info available
Lee JJ
No affiliation info available
Kim CW
No affiliation info available

MeSH

Administration, InhalationAnimalsChemistry, PharmaceuticalCrystallizationDelayed-Action PreparationsDiabetes Mellitus, ExperimentalDrug Delivery SystemsInsulinLungMaleMicrospheresRatsRats, Sprague-Dawley

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15158896

Citation

Kwon, Jai-Hyun, et al. "Insulin Microcrystal Suspension as a Long-acting Formulation for Pulmonary Delivery." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 22, no. 2-3, 2004, pp. 107-16.
Kwon JH, Lee BH, Lee JJ, et al. Insulin microcrystal suspension as a long-acting formulation for pulmonary delivery. Eur J Pharm Sci. 2004;22(2-3):107-16.
Kwon, J. H., Lee, B. H., Lee, J. J., & Kim, C. W. (2004). Insulin microcrystal suspension as a long-acting formulation for pulmonary delivery. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 22(2-3), 107-16.
Kwon JH, et al. Insulin Microcrystal Suspension as a Long-acting Formulation for Pulmonary Delivery. Eur J Pharm Sci. 2004;22(2-3):107-16. PubMed PMID: 15158896.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin microcrystal suspension as a long-acting formulation for pulmonary delivery. AU - Kwon,Jai-Hyun, AU - Lee,Byung-Ha, AU - Lee,Jae-Jeong, AU - Kim,Chan-Wha, PY - 2003/07/22/received PY - 2003/12/03/revised PY - 2004/02/19/accepted PY - 2004/5/26/pubmed PY - 2005/1/19/medline PY - 2004/5/26/entrez SP - 107 EP - 16 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 22 IS - 2-3 N2 - Pulmonary delivery provides the most promising non-parenteral route of insulin administration. Insulin was used as a model protein to demonstrate the feasibility of using protein crystals for the pulmonary delivery of a sustained-release protein drug formulation. Insulin microcrystals with a mean diameter of 3 microm were prepared using a seed zone method. The yield of crystallization was very high (95.8 +/- 0.97%), and the microcrystals were recovered with high efficiency (>98%) by centrifugation. Morphological examination using scanning electron microphotography showed the microcrystals to be of a homogeneous rhombohedral shape, with some rhombus forms, without aggregates. After the administration of 32 U/kg of the microcrystal suspension to STZ-induced diabetic SD rats by intratracheal instillation, the blood glucose levels were reduced and hypoglycemia was prolonged over 13 h, as compared to the insulin solution. The percent minimum reductions of the blood glucose concentration (% MRBG) produced by the microcrystal suspension and insulin solution reached 36.5 and 37.2%, respectively, of the initial level, and the percent total reductions in blood glucose (% TRBG(13 h)) were 34.4 and 25.0%, respectively. In the case of inhalation using a sieve-type ultrasonic nebulizer, the % MRBG produced by the microcrystal suspension and insulin solution were 21.7 and 26.3%, respectively, of the initial level, and the % TRBG(13 h) were 66.7 and 58.4%, respectively. However, the hypoglycemic effects of the microcrystal suspension were prolonged over 7 h, which compares favorably with the insulin solution (P<0.5 by unpaired t-test). These results could be attributed to the sustained-release of insulin from the microcrystals, which were deposited widely throughout the entire lung. SN - 0928-0987 UR - https://www.unboundmedicine.com/medline/citation/15158896/Insulin_microcrystal_suspension_as_a_long_acting_formulation_for_pulmonary_delivery_ DB - PRIME DP - Unbound Medicine ER -