Formation of ion pairing as an alternative to improve encapsulation and stability and to reduce skin irritation of retinoic acid loaded in solid lipid nanoparticles

Abstract

This work aims to investigate the influence of the formation of ion pairing between all-trans retinoic acid (RA) and a lipophilic amine (stearylamine; STE) on the drug encapsulation efficiency (EE) and stability of solid lipid nanoparticles (SLNs). The SLNs were characterized for EE and size. The EE and particle size were significantly improved and reduced, respectively, when the surfactant or co-surfactant concentration increased. However, while the formulation without STE allowed only 13% of RA encapsulation, the EE for RA-STE-loaded SLNs was 94%. The stability studies showed a significant decrease in EE for the SLNs without STE, while, for SLNs loaded with RA and STE, the EE remained constant after 360 days. The interactions among ion pairing components and the lipid matrix were investigated through small-angle X-ray scattering (SAXS). The SAXS analysis revealed the presence of RA in the crystalline form in SLNs without ion pairing, while crystalline RA was not observed in SLNs loaded with RA/amine. Skin irritation studies showed that the SLNs loaded with the ion pairing were significantly less irritating when compared to the marketed RA-cream. This novel SLN formulation represents a promising alternative for topical treatment of acne with RA.

Formation of ion pairing as an alternative to improve encapsulation and anticancer activity of all-trans retinoic acid loaded in solid lipid nanoparticles

“…19 Considering the intended use of SLNs (intravenous administration), Tween 80™ was selected as surfactant. Briefly (batch 20 mL), the oily phase, composed of Compritol (400 mg), cholesterol (40 mg), Tween 80™ (300 mg), RA (10 mg), and the aqueous phase were heated separately to 85°C.…”

“…The data reported were particle size, evaluated as the intensity obtained from three repeat measurements, and the polydispersity index. 19 …”

“…19 This method was based on the determination of RA concentration in the SLNs before (total RA) and after filtration (cellulose ester membrane, 0.45 µM, Millipore). The RA crystals, usually measuring a few micrometers across, present characteristic forms and can be easily distinguished from SLNs.…”

“…Among the tested amines, stearylamine (SA) ( Figure 1C), a lipophilic amine, provided the highest encapsulation. 18,19 These previous investigations were performed aiming for the development and evaluation of formulations for the topical treatment of acne. We hypothesized that SLNs loaded with RA, and different amines could be an interesting alternative for enabling intravenous administration of RA for cancer treatment.…”

A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles

“…SLN's have been investigated for parenteral drug delivery and have successfully been demonstrated to possess good pharmacokinetics and tissue distribution characteristics when used for drugs such as doxorubicin and tobramycin (Bargoni et al 2001;Zara et al 2002). SLN based topical formulations have also been developed for cosmetic applications, and some products are already being marketed commercially (Castro, et al 2009;Müller et al 2002). Notably, SLN's have been investigated for oral drug delivery and have been shown to exhibit good release characteristics and systemic bioavailability of the encapsulated drugs (Demirel et al 2001;Yang, et al 1999).…”