Abstract
Solid core drug delivery systems (SCDDS) were prepared for the oral delivery of biomolecules using mesoporous silica as core, bovine haemoglobin (bHb) as model drug and supercritical fluid (SCF) processing as encapsulation technique. The use of organic solvents or harsh processing conditions in the development of drug delivery systems for biomolecules can be detrimental for the structural integrity of the molecule. Hence, the coating on protein-immobilised particles was performed via supercritical carbon dioxide (scCO2) processing at a temperature lower than the melting point of myristic acid (MA) to avoid any thermal degradation of bHb. The SCDDS were prepared by bHb immobilisation on mesoporous silica followed by myristic acid (MA) coating at 43 °C and 100 bar in scCO2. bHb-immobilised silica particles were also coated via solvent evaporation (SE) to compare the protein release with scCO2 processed formulations. In both cases, MA coating provided required enteric protection and restricted the bHb release for the first two hours in simulated gastric fluid (SGF). The protein release was immediate upon the change of media to simulated intestinal fluid (SIF), reaching 70% within three hours. The release from SCF processed samples was slower than SE formulations, indicating superior surface coverage of MA on particles in comparison to the SE method. Most importantly, the protein conformation remained unchanged after the release from SCDDS as confirmed by circular dichroism. This study clearly demonstrates that the approach involving protein immobilisation on silica and scCO2 assisted melt-coating method can protect biomolecules from gastric environment and provide the required release of a biologic in intestine without any untoward effects on protein conformation during processing or after release.
Highlights
Parenteral administration is the most common route for therapeutic peptide/protein delivery [1]
Solid core drug delivery systems (SCDDS) for the oral delivery of biomolecules was prepared by the bovine haemoglobin (bHb) immobilisation on mesoporous silica followed by coating of myristic acid via scCO2-assisted melt coating and conventional solvent evaporation methods
The advantage of using scCO2 processing was to obtain the coating at a lower temperature than the melting point of myristic acid (MA) at atmospheric pressure and to avoid the use of an organic solvent
Summary
Parenteral administration is the most common route for therapeutic peptide/protein delivery [1]. Polyesters, polyanhydrides, and naturally occurring materials, including gelatin, alginate and chitosan, are amongst the most commonly used polymers to develop sustained release protein formulations [3] Most of these still fail to answer issues related to cost, frequent injections and low patient compliance. Protein denaturation due to stomach acid, enzymatic degradation, mucocilliary clearance and impermeability across the intestinal wall are well known issues associated with oral delivery Another major challenge in developing novel drug delivery systems for biologics is linked to exposure of biomolecules to harsh processing conditions such as high shear stress, temperature and organic-water solvent interface, which may lead to structural changes in proteins [5]. TThhee ddaattaa ffoorr bbHHbb aaddssoorrppttiioonn oonn ssiilliiccaa ppaarrttiicclleess wwaass fifitttteedd wwiitthh bbootthh LLaannggmmuuiirr aanndd FFrreeuunnddlliicchh mmooddeellss,, rreessuullttiinngg iinn RR22 vvaalluueess ooff 00..77991155 aanndd 00..99886644,, rreessppeeccttiivveellyy. An increase in the point of zero charge (PZC) for silica from pH 1.6 for bare particles to 6.7 for protein immobilized particles (closer to the IEP of bHb) indicated coverage of particle surface with bHb molecules
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
