Dual delivery nanosystem for biomolecules. Formulation, characterization, and in vitro release

Abstract

Because of the biocompatible and biodegradable properties of poly (lactic-co-glycolic acid) (PLGA), nanoparticles (NPs) based on this polymer have been widely studied for drug/biomolecule delivery and long-term sustained-release. In this work, two different formulation methods for lysozyme-loaded PLGA NPs have been developed and optimized based on the double-emulsion (water/oil/water, W/O/W) solvent evaporation technique. They differ mainly in the phase in which the surfactant (Pluronic F68) is added: water (W-F68) and oil (O-F68). The colloidal properties of these systems (morphology by SEM and STEM, hydrodynamic size by DLS and NTA, electrophoretic mobility, temporal stability in different media, protein encapsulation, release, and bioactivity) have been analyzed. The interaction surfactant-protein depending on the formulation procedure has been characterized by surface tension and dilatational rheology. Finally, cellular uptake by human mesenchymal stromal cells and cytotoxicity for both systems have been analyzed. Spherical hard NPs are made by the two methods However, in one case, they are monodisperse with diameters of around 120nm (O-F68), and in the other case, a polydisperse system of NPs with diameters between 100 and 500nm is found (W-F68). Protein encapsulation efficiency, release and bioactivity are maintained better by the W-F68 formulation method. This multimodal system is found to be a promising "dual delivery" system for encapsulating hydrophilic proteins with strong biological activity at the cell-surface and cytoplasmic levels.

Tailor-Made Fluorinated Ionic Liquids for Protein Delivery

“…Although the results obtained with cholinium were not the expected, the encapsulation efficiencies with the other FILs at the higher concentration were all above 69.4%, with a maximum value of 83.4% achieved for [C 2 C 1 py][C 4 F 9 SO 3 ]. These encapsulation efficiencies are relatively higher than others obtained with several traditional platforms such as microspheres and PLGA-based materials (ranging from 10.9% to 83%) [41][42][43][44] and very similar to the high entrapment rates (72-91%) of biomolecules in liposomes [45].…”

Formulation, Colloidal Characterization, and In Vitro Biological Effect of BMP-2 Loaded PLGA Nanoparticles for Bone Regeneration

“…These systems can be applied not only in tissue regeneration but also in very diverse therapies: Anticancer drug delivery, infections, inflammatory diseases, or gene therapy [3]. Despite this great potential, certain applications, especially in protein encapsulation, are hindered by problems, such as an uncontrolled release profile and protein denaturation [8,9,10,11].…”

“…The water-in oil-in water (W/O/W) double emulsion method is an “emulsion solvent evaporation” technique frequently used to encapsulate hydrophilic molecules as proteins in PLGA NPs [6,12]. The appropriate choice of organic solvents, the use of polymer-surfactant blends, and the addition of stabilizer-protective agents have proved to be key aspects for optimizing the resulting systems [9,11]. Additionally, a surface specific functionalization can be used to improve their versatility, allowing the chemical surface immobilization of different molecules in order to confer targeting or adhesive properties to these nanocarriers [13].…”

“…Thus, within this scenario, in the present work, we seek to optimize a nano-particulate system in order to carry out and control the release of BMP-2 using as a starting point the synthesis procedure of a lysozyme-loaded NP system, previously described for the encapsulation of that model protein [11]. Also, to encapsulate BMP-2, we prepared a second system in which this protein was co-adsorbed with bovine serum albumin onto the surface of empty NPs.…”

The possibility of healing alveolar bone defects with simvastatin thermosensitive gel: in vitro/in vivo evaluation

“…Generally, biodegradable delivery system of natural polysaccharides have attracted much attention because of their good biocompatibility, biodegradability, and protective actions. 14 , 15 Another interesting approach to oral drug delivery is the use of hydrogel systems. Hydrogels are hydrophilic polymers that can be swollen in water or water solvents.…”