Project description
The development of innovative products of peptide nature for oral administration is extremely complex due to the unfavorable physicochemical properties of the molecules, as well as to the existence of strong biological barriers, resulting in a deficient pharmacokinetics and, therefore, low bioavailability. Currently, most peptide pharmaceutical products are presented in injectable form. There are few companies that commercialize oral administration peptides, which exhibit very low bioavailability (0.5 to 2%). These formulations usually combine TPE (transient permeation enhancers) with protease inhibitors, or pH modifiers, in traditional dosage forms that are usually covered with acid-resistant polymers. The most notable examples are oral semaglutide for type II diabetes (Rybelsus®) based on a combination of patented TPE called SNAC, as well as recently approved oral octreotide (Mycappsa®) for acromegaly, which occurs in the form of peptide oil suspension with a combination of medium-chain fatty acids / glycerides such as TPE.
CryoXpand® technology is based on the properties of fast-expanding liquid CO2 as a freezing, atomization, spheronization and drying agent to produce fine microparticles and possibly powder-shaped nanoparticles. The cryogenic conditions generated by the expansion of CO2 during spraying allow the processing of different types of materials and facilitate the formation of physical compounds of lipids and polymers, with specific characteristics and functions, which can be applied in micronised drug delivery systems with improved biopharmaceutical properties. The technology allows spraying combinations of excipients, generating amphiphilic microparticles, which allows to jointly encapsulate fat-soluble and water-soluble active molecules at low processing temperatures. In addition, suitable combinations of lipids and other functional excipients can be selected to facilitate the release of biomolecules with the desired profile. Among molecules of very low availability, some classes of peptides that can benefit from a successful result of this project have been identified.
The project will focus on the design, research and initial development of prototypes of innovative products for the oral administration of peptides, through the use of the CryoXpand® technique.
The objective is to investigate the application of the concept of composite materials in the formulation of peptides for oral use, and to study the impact of cryopulverization process conditions, identifying critical parameters that can affect the characteristics of the microparticles obtained.
It aims to conceptualize and investigate composite lipid systems, developed using CryoXpand® technology, and produce solid formulated microspheres for encapsulation of peptide active molecules. The formulations will be designed to protect the peptide active principle and prevent its degradation, facilitating its release into the intestine so that the molecule remains protected, while improving its absorption through the intestinal membranes. As composites of interest for this project, peptides of the class of GLP-1 analogues (for example, liraglutide) or GLP-2 and the class of echinocandines have been identified. Its development in oral dosage forms remains a challenge for the reasons cited above, but at the same time it is an excellent opportunity for the development of products of high-value therapeutic indications such as type II diabetes and obesity. Another possible candidate belongs to the class of echinocandines, state-of-the-art lipo-peptides of the antifungal class, for the treatment of severe systemic candidiasis and other opportunistic fungal infections linked, for example, to cancer treatments. In summary, the objective of the innovative project will focus on the design, research and development of product prototypes in the form of solid micro- or nanoparticles, which will contain active molecules of lipopeptide nature. The specific selection of combinations with excipients will allow optimizing the biopharmaceutical properties of the active ingredients contained (drugs or other molecules with low oral bioavailability). (review)
