Delivery of salmon calcitonin using a microneedle patch

Abstract

Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL.min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL.min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL.min). Tmax (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections.

Novel Delivery Systems for Improving the Clinical Use of Peptides

“…Microneedles offer four different approaches, all of which have been applied to peptides: 1) pretreatment with microneedles followed by application of the formulation Mohammed et al, 2014); 2) dissolving microneedles that release the peptide rapidly and simultaneously to the microneedle dissolution (Fukushima et al, 2011;Ling and Chen 2013); 3) coated microneedles releasing their peptide coating (Cormier et al, 2004;Tas et al, 2012); and 4) hollow microneedles enabling microinjections (Davis et al, 2005;Wang et al, 2006;Norman et al, 2013). When commercially available microneedle rollers were used as pretreatment to create micropores into rat skin followed by the application of insulin solution, the microneedles rollers could increase skin permeability for insulin-lowering blood glucose levels .…”

“…When commercially available microneedle rollers were used as pretreatment to create micropores into rat skin followed by the application of insulin solution, the microneedles rollers could increase skin permeability for insulin-lowering blood glucose levels . Tas et al (2012) used coated steel microneedles with salmon calcitonin together with trehalose (for improved protein stability) and compared the microneedle administration with subcutaneous injection in rats. The salmon calcitonin AUC values of microneedle administration and subcutaneous injection were not significantly different (Tas et al, 2012).…”

“…Tas et al (2012) used coated steel microneedles with salmon calcitonin together with trehalose (for improved protein stability) and compared the microneedle administration with subcutaneous injection in rats. The salmon calcitonin AUC values of microneedle administration and subcutaneous injection were not significantly different (Tas et al, 2012). Compared with intranasal administration, the AUC after microneedle administration was 13-fold higher than after intranasal administration.…”

Recent advances in topical delivery of proteins and peptides mediated by soft matter nanocarriers

“…Topical applications could prolong their halflife and allow for a controlled release from the formulations which helps to maintain steady blood concentrations (Amsden and Goosen, 1995). Based on these considerations, the dermaland transdermal delivery of biomacromolecules such as calcitonin (Chang et al, 2000;Manosroi et al, 2013;Tas et al, 2012) and insulin (Hadebe et al, 2014;Ling and Chen, 2013;Sintov and Wormser, 2007) have repeatedly been pursued. Moreover, using topically applied biomacromolecules for the treatment of severe skin diseases is a rather new but highly interesting approach.…”

Recent Advances in Physical Approaches for Transdermal Penetration Enhancement

“…Rapid dissolution and absorption of salmon calcitonin by dermal capillaries resulted in Tmax 50% shorter than subcutaneous injections. Nevertheless further research in optimizing coating microneedles may facilitate administration of salmon calcitonin and other peptides without the need for hypodermic injections [34]. It was further proposed that Bioneedles TM can be used as a good alternative for vaccination without syringes and needles.…”