(345d) In Vivo Analysis of Insulin Delivery Using CPEs Designed Via In Silico QSPR Approach

The inconvenience of multiple-injection regimens for diabetes patients desiring intensive management and the reluctance of patients with poorly controlled type 2 diabetes mellitus to start insulin therapy have spurred the development of alternative, needle-free delivery methods.  Transdermal drug delivery is gaining importance in the recent years due to its advantages over other traditional methods.  A patch impregnated with insulin placed on the skin may be able to deliver a continuous low dose of basal insulin; however, since insulin is a large molecule, it does not permeate the skin easily.  Altering the characteristics of the skin by using chemicals called penetration enhancers is one of the promising ways to breach the skin’s barrier to drugs.  Using this concept, we have reported on the methodology of predicting CPEs using improved algorithms for non-linear, quantitative structure-property relationship (QSPR) models based upon representative molecular properties [1-7].  The predicted molecules were extensively tested for cytoxicity and ex vivo delivery.  This study focuses in evaluating the in vivo efficacy delivering insulin across the skin with and without CPEs in a rodent model.  Rats were starved eight hours before the application of the patch and then blood glucose levels were monitored.  After five days we evaluated the overall body weight change, hepatotoxicity and skin toxicity.  Our findings through animal trials indicate proven efficacy of the newly designed CPEs.

References

[1] Yerramsetty KM, Rachakonda VK, Neely BJ, Madihally SV, Gasem KAM.  Effect of Different Enhancers on the Transdermal Permeation of Insulin Analog. International Journal of Pharmaceutics. 398 (1-2): 83-92. 2010.

[2]. Yerramsetty KM, Neely BJ, Madihally SV, Gasem KAM.  A Skin Permeability Model of Insulin in the Presence of Chemical Penetration Enhancer.  International Journal of Pharmaceutics. 388(1-2):13-23. 2010.

[3] Godavarthy SS, Yerramsetty KM, Rachakonda VK, Neely BJ, Madihally SV, Robinson Jr RL, Gasem KAM.  Design for Improved Permeation Enhancers for Transdermal Drug Delivery.  Journal of Pharmaceutical Sciences.  98(11):4085-4099. 2009.

[4] Neely BJ, Golla S, Whitebay E, Madihally SV, Robinson Jr RL, Gasem KAM.  Non-linear Quantitative Structure-Property Relationship Modeling of Permeation Coefficients.  Journal of Pharmaceutical Sciences.  98(11):4069-4084. 2009.

[5]  Golla S, Madihally SV, Robinson RL Jr., Gasem KAM.  Quantitative Structure-Property Relationship Modeling of Skin Sensitization: A Quantitative Prediction.  Toxicology In vitro.  23(3):454-65.  2009.

[6] Golla S, Madihally SV, Robinson RL Jr., Gasem KAM.  Quantitative Structure-Property Relationship Modeling of Skin Irritation.  Toxicology In vitro. 23(1):176-184. 2009.

[7] Rachakonda VK, Yerramsetty KM, Madihally SV, Robinson RL Jr, Gasem KAM.  Screening of Chemical Penetration Enhancers for Transdermal Drug Delivery using Electrical Resistance of Skin.  Pharmaceutical Research.  25(11):2697-704. 2008.