Encapsulation of protein nanoparticles into uniform-sized microspheres formed in a spinning oil film

Abstract

A new spinning oil film (SOF) solid-in-oil-in-oil emulsion process was developed to produce uniform-sized proteinloaded biodegradable microspheres. A thin SOF on a cylindrical rotor was used to shear droplets from a nozzle tip to control droplet size. The resulting microspheres with low polydispersity (6%) produced a low burst (6%-11%) release even at high loadings (13%-18% encapsulated solids, 8%-12% protein). The SOF process had a high yield and did not require the presence of water, which can cause protein denaturation, or surfactants, which may be unwanted in the final product. Amorphous protein and crystalline excipient solids were encapsulated into 3 different polymers, giving a homogenous drug distribution throughout the microspheres, and an essentially complete protein encapsulation efficiency (average = 99%). In contrast, large burst release was observed for polydisperse microspheres produced by a conventional emulsification technique, particularly for microspheres smaller than 25 μm in diameter, which gave 93% burst at 15% loading. The uniform encapsulation of high loadings of proteins into microspheres with low polydispersity in an anhydrous process is of practical interest in the development of controlled-release protein therapeutics.

Preparation, characterization and in-vitro evaluation of sustained release protein-loaded nanoparticles based on biodegradable polymers

“…We studied a pretty long period for studying sustained release of protein. However, literature showed variable protein release study period from 35 days to 70 days (Zhu and Schwendeman 1999; Leach et al 2005). …”

The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review

“…Comparison of SLN and NLC particle size and size stability Particle size and size distribution are two important criteria of nanoparticles as these factors affect drug release rate, bio-distribution, mucoadhesion, cellular uptake of water and buffer exchange to the interior of the nanoparticles, and protein diffusion. 28,29 Microspheres with a narrow size distribution are necessary to optimize clinical outcomes. 30 The particle size and size distribution are other important indices for evaluating a colloidal dosage form upon storage.…”

Emulsion Templating of Poly(lactic acid) Particles: Droplet Formation Behavior

“…Removal of solvent can be achieved either by the ambient solvent extraction/evaporation method 4 or by the freezing method, where the solvent to be removed is frozen and gradually heated under vacuum, leaving behind precipitated solid microspheres. 5 Biodegradable microparticles are of interest primarily for medical and pharmaceutical applications, where they have been used for the encapsulation and controlled release of a wide range of pharmaceutical actives (rifampicin, 6 buserilin, 7 paclitaxel, 8 tetracycline, 9 etc. ), encapsulation of biological actives such as plasmid DNA, 10,11 ultrasound and molecular imaging, 12,13 ultrasound-triggered drug release, 14 cell cultivation in tissue engineering, 15,16 fabrication of scaffolds for bone tissue repair applications, 17,18 and fabrication of composite coatings for implantable devices.…”