Poly(vinyl alcohol) as Emulsifier Stabilizes Solid Triglyceride Drug Carrier Nanoparticles in the α-Modification

Abstract

Colloidal dispersions of solid lipids are under intensive investigation as drug delivery systems. In the present study, poly(vinyl alcohol) (PVA) was tested as an alternative stabilizer for triglyceride nanoparticles. The dispersions contained 10% triglyceride (trimyristin or tristearin) and 5% PVA and were prepared by high pressure melt homogenization. The nanoparticle dispersions were investigated for their thermal behavior and storage stability with special regard to the polymorphic transitions of the triglyceride matrix, including effects of storage temperature and the incorporation of model drugs (diazepam, ubidecarenone) using photon correlation spectroscopy, differential scanning calorimetry, X-ray diffraction, and transmission electron microscopy. The release of the model drug diazepam from a selected nanoparticle dispersion was investigated with differential pulse polarography. Triglyceride nanoparticles prepared with PVA displayed an unusually high stability of the metastable alpha-modification depending on the type of triglyceride and the storage conditions. In tristearin nanoparticles, the alpha-polymorph was stable for at least 9 months at refrigerator temperature and the particles exhibited a spherical shape in electron microscopic investigations. Moreover, the alpha-form in PVA-stabilized tristearin nanoparticles seemed to be highly disordered, as it did not lead to a pronounced small-angle X-ray reflection. Storage at higher temperatures led to a transformation of the particles into the beta-modification, which usually was accompanied by an increase in particle size. Incorporation of the two model drugs did not change the crystal modification of the particle matrix to a large extent. After dilution into a large volume of release medium, a large fraction of the model drug diazepam was released immediately but there was no further release over several hours. The high stability of PVA-stabilized tristearin nanoparticles with regard to particle size and alpha-modification makes them suitable as a model for investigations on the influence of the polymorphic form (e.g., in comparison with nanoparticles in the more stable beta-modification) on pharmaceutically important parameters such as drug load and drug release.

Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans

“…The nanoparticles show unusually high stability in the presence of PVA. 59,60 The simple and straightforward preparation protocol makes development of a AmB−PGA formulation an excellent strategy. The AmB−PGA formulation was found to be readily and rapidly soluble in water ( Table 1).…”

“…The release pattern of the AmB−PGA nanoparticles in PBS and serum was similar to the stability data of AmBisome. The high stability of the AmB−PGA formulation could be attributed (in part) to the stabilizing properties of the PVA 59,60 used in the preparatory cocktail during formation of the nanoparticles.…”

Lipid nanoparticles for the delivery of poorly water-soluble drugs

“…on storage of the nanoparticle dispersions) has to be taken into consideration. [42][43][44][45] The course of polymorphic transitions depends on the type of matrix lipid and can be modified by other components of the dispersions such as emulsifiers or incorporated drugs. [45][46][47][48][49][50] Polymorphic transitions may involve profound alterations of lipid packing and thus of the internal structure of the nanoparticles, which might have negative consequences for drug loading.…”

Comprehensive Interpretation of Nanostructured Lipid Carriers (Nlc): A Promising New Generation Lipid Carrier for the Delivery of Cancer Chemotherapeutics

“…[42][43][44] Usually, ethanol, propylene glycol and pentylene glycol are used as preservatives in NLC. it's been ascertained that NLC preserved with 5-10% w/w propylene glycol didn't show any significant amendment in particle size or in zeta potential in comparison with the non-preserved formulation.…”