Advance in transdermal delivery of calcitonin using nanostructured lipid carrier-based emulgel

Abstract

Context: Peptide-protein drugs have a very important role as therapeutic agents for various diseases. However, their therapeutic use has many barriers to delivery, such as large molecular weight, reduced stability during the manufacturing process and storage, and poor absorption when administered orally. One of peptide-protein drugs is calcitonin, a polypeptide of 32 amino acids used to overcome high levels of calcium in the blood, such as hyperparathyroidism. Nevertheless, drug delivery is still challenging to develop. Aims: To evaluate a calcitonin nanostructured lipid carrier-based emulgel, which could penetrate through the stratum corneum, and meet the stability requirements. Methods: Four formulas of calcitonin nanostructured lipid carrier (NLC) were prepared by the double emulsion-evaporation method, then all formulas were characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, and particle morphology. Calcitonin NLCs were then formulated into NLC-based emulgel. Further, in vitro penetration and stability of NLC calcitonin emulgel studies were conducted. Results: The 75:1 ratio of total lipid to the drug (F2) was optimal for calcitonin-loaded NLC with a particle size of 135.6 nm, an index polydispersity of 0.1, the zeta potential of 34.7 mV, and an entrapment efficiency of 99.6%. According to the percutaneous penetration study, the calcitonin NLC-based-emulgel resulted in a fivefold enhancement compared to the non-NLC calcitonin emulgel. Moreover, the stability study illustrated calcitonin levels after six months were 46.09-60.95% and 43.45-68.59% at storage conditions of 5 ± 3ºC and 25 ± 2ºC/RH 60 ±5 %, respectively. Conclusions: The calcitonin NLC-based-emulgel produced a fivefold enhancement permeation through the stratum corneum.