Influence of Polymorphic Transformations on Gelation of Tripalmitin Solid Lipid Nanoparticle Suspensions

Abstract

Solid lipid nanoparticle (SLN) suspensions, which consist of submicron-sized crystalline lipid particles dispersed within an aqueous medium, can be used to encapsulate, protect and deliver lipophilic functional components. Nevertheless, SLN suspensions are susceptible to particle aggregation and gelation during their preparation and storage, which potentially limits their industrial utilization. In this study, we examined the aggregation and gelation behavior of SLN suspensions composed of 10 wt% tripalmitin particles (r \ 150 nm) stabilized by 1.5% Tween 20. The tripalmitin and aqueous surfactant solution were homogenized above the lipid melting temperature and cooled under controlled conditions to initiate SLN formation. The aggregation and gelation of SLN suspensions during storage was then examined by shear rheometry, differential scanning calorimetry (DSC), light scattering and microscopy. Rheology measurements indicated that gelation times decreased with increasing storage temperature, e.g., samples formed weak gels after 62, 23, and 10 min at 1, 5, and 10°C, respectively. DSC revealed increasingly rapid a-to b-polymorphic transformations in SLN dispersions stored at 1, 5, and 10°C, respectively. We propose that the observed aggregation and gelation of SLN suspensions are associated with a change in the shape of the nanoparticles from spherical (a-form) to non-spherical (b-form) when they undergo the polymorphic transition. When they change shape there is no longer sufficient surfactant present to completely cover the lipid phase, which promotes particle aggregation through hydrophobic attraction. Our results have important implications for the design and fabrication of stable SLN suspensions.

Development and Characterization of Piper Retrofractum Extract Loaded Mucoadhesive Nanostructured Lipid Carriers for Topical Oral Drug Delivery

“…This phenomenon can be described by polymorphic transformation of the inner lipid matrix of NLCs. Jenning et al reported that the low temperature could induce the polymorphic transition of MCT from the amorphous form ( -form) to crystallized form ( -form), leading to the transformation of spherical to platelet shaped particles [26,27]. In addition, Helgason et al stated that the surfactants required to cover and stabilize the newly created interfaces may not be able to diffuse rapidly enough to adsorb at the newly formed lipid crystalline interfaces, leading to increased mean particle size due to flocculation [28].…”

Extending Emulsion Functionality: Post-Homogenization Modification of Droplet Properties

“…Lipid particles may retain an approximately spherical shape, or they may undergo appreciably changes in morphology depending on the cooling rate, holding temperature, oil type, and emulsifier type. These changes in particle morphology can lead to drastic changes in the rheology and stability of lipid nanoparticle suspensions [61,62].…”

Effect of Cooling and Heating Rates on Polymorphic Transformations and Gelation of Tripalmitin Solid Lipid Nanoparticle (SLN) Suspensions

“…The microstructure of SLN suspensions was also observed using an optical microscope (Nikon microscope Eclipse E400, Nikon, Japan). 29 …”

“…[25][26][27][28] We recently investigated the mechanism of gelation in tripalmitin SLN suspensions and found that the incidence of gelation at different storage temperatures was associated with a polymorphic transition to the β-form, which increased the overall particle surface area and promoted particle aggregation through hydrophobic attraction of lipids at surfactant-free patches. 29 To make stable SLN suspensions for the encapsulation and protection of sensitive bioactive ingredients, it is necessary to either retard the polymorphic transition or to control the aggregation stability. 24 There have been many studies on modification of the crystallization and polymorphic behavior and stability of lipids in emulsions as well as SLN by varying surfactants, 19,20,[30][31][32][33][34][35] lipid composition, 36 particle size and distribution, 30,37,38 aqueous phase composition, and application of shear.…”