Biology subjects

Lima, L. M.

Publications and source records attributed to Lima, L. M..

2 recordsLinked to original sources

bioRxiv2018

Sustained release and pharmacologic effects of human glucagon-like peptide-1 and liraglutide from polymeric microparticles.

The GLP-1 class of peptide agonists has been shown to exert regulatory key roles in both diabetes, obesity and related complications. Given the short half-life of GLP-1 its use has been historically discouraged. We developed polymeric microparticles loaded with either human GLP-1 (7-37) or liraglutide peptides by double emulsion and solvent evaporation approach. The size distribution of all formulations was of about 30-50 m. The in vitro kinetic release assays showed a sustained release of the peptides extending up to 30 to 40 days with varying profiles. Morphologic analysis demonstrated a more regular particle surface for those comprising polymers PLA, PLA-PEG and PLGA. In vivo evaluation in Swiss male mice demonstrated a similar extension of effect of decreasing in body weight gain for up to 25 days after a single subcutaneous administration of either hGLP-1 or liraglutide peptide-loaded microparticles (200 g peptide / kg body weight) compared to controls. These demonstrate the effectiveness of hGLP-1 as a therapeutic agent in long-term, continuous release from peptide-load microparticles, and thus its plausibility as an unmodified therapeutic agent.

pharmacology and toxicology↗

bioRxiv2017

Physico-chemical properties of co-formulation of insulin with pramlintide

Since the discovery of amylin its use has been discouraged by the inadequacy of the protocol involving multiple injections in addition to insulin. While a combined fixed-dose formulation is thus highly desirable, it has long been limited due to incompatibility as historically documented. We have investigated the compatibility of regular and fast-acting insulin analogues (Aspart, AspB28, and LisPro, LysB28ProB29) with the amylin analogue pramlintide. Insulin interacts with pramlintide, forming heterodimers as probed by electrospray ionization - ion mobility spectrometry-mass spectrometry. While their interaction is likely to delay the amyloid aggregation of pramlintide in phosphate-buffered solution pH 7.0, they do not prevent aggregation at this condition. At acidic sodium acetate solution pH 5.0, combination of pramlintide and the fast-acting insulin analogues become stable against amyloid aggregation. The co-formulated product at high concentration of both pramlintide (600 g/mL,150 M) and LisPro insulin (50 IU/mL, 300 M) showed also stability against amyloid aggregation. These data indicate a potential for the development of a co-formulation of fast-acting LisPro insulin with pramlintide, which could bring benefits for the combined therapy.\n\nAbbreviations

biophysics↗