An Efficacy Assessment Of The Cardioprotective Effects Of Alpha-calcitonin Gene Related Peptide (alpha CGRP) Encapsulated Alginate Microcapsules In A Murine Model Of Heart Failure

The cardioprotective role of a neuropeptide, alpha-calcitonin gene related peptide (αCGRP), has been established in a variety of cardiovascular diseases. To increase the bioavailability of the circulating peptide, we created a peptide delivery system by encapsulating αCGRP in an alginate biopolymer and showed that subcutaneous delivery of alginate-αCGRP microcapsules (αCGRP dose= 6 mg/kg/mouse) on alternate days, up to 28 days, significantly protected hearts at pathophysiological levels in a transverse aortic constriction (TAC) pressure-overload induced heart failure murine model. The present study was performed to determine if weekly subcutaneous delivery of alginate-αCGRP microcapsules exhibited similar cardioprotective effects in TAC-mice as observed in our previous study with alternate days dose delivery scheme. This study is crucial to shed light on the efficacy of these microcapsules. An electrospray method was used to prepare alginate-αCGRP microcapsules of 200 μm diameter. Male C57BL6 mice were divided into four groups (3 mice/group): i- sham, ii- sham-alginate-CGRP, iii- TAC, and iv- TAC-alginate-CGRP. Mice from TAC and TAC-alginate-CGRP groups underwent TAC procedure. Two days post-TAC, alginate-αCGRP microcapsules (αCGRP dose= 6 mg/kg/mouse) were administered subcutaneously once a week, up to 4 weeks, in the respective alginate-CGRP groups of mice. Short-axis echocardiography was performed to evaluate cardiac functions. After 28 days of microcapsules delivery, calculated percent fractional shortening (FS) and ejection fraction (EF) in mice were (in ±SD)- sham: FS= 47.6 ± 0.9, EF= 79.8 ± 0.9; sham-alginate-CGRP: FS= 47.3 ± 1.9, EF= 79.1 ± 2; TAC: FS= 34.1 ± 4.7, EF= 63.6 ± 7.1; TAC-alginate-CGRP: FS= 32.2 ± 2.3, EF= 61.0 ± 3.4. These echo data demonstrate that TAC heart failure mice had the usual significantly reduced cardiac functions, however weekly delivery of alginate-αCGRP microcapsules showed no improvement in heart performance in the TAC-mice. Combined results from our present and previous studies suggested that alginate-αCGRP microcapsules delivery on alternate days, but not weekly, is the most efficacious choice to achieve cardioprotective effects of αCGRP against pressure-induced heart failure in mice.