Solid Dispersion of Ursolic Acid in Gelucire 50/13: a Strategy to Enhance Drug Release and Trypanocidal Activity

Abstract

Solid dispersions (SDs) are an approach to increasing the water solubility and bioavailability of lipophilic drugs such as ursolic acid (UA), a triterpenoid with trypanocidal activity. In this work, Gelucire 50/13, a surfactant compound with permeability-enhancing properties, and silicon dioxide, a drying adjuvant, were employed to produce SDs with UA. SDs and physical mixtures (PMs) in different drug/carrier ratios were characterized and compared using differential scanning calorimetry, hot stage microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size, water solubility values, and dissolution profiles. Moreover, LLC-MK2 fibroblast cytotoxicity and trypanocidal activity evaluation were performed to determine the potential of SD as a strategy to improve UA efficacy against Chagas disease. The results demonstrated the conversion of UA from the crystalline to the amorphous state through XRD. FTIR experiments provided evidence of intermolecular interactions among the drug and carriers through carbonyl peak broadening in the SDs. These findings helped explain the enhancement of water solubility from 75.98 μg/mL in PMs to 293.43 μg/mL in SDs and the faster drug release into aqueous media compared with pure UA or PMs, which was maintained after 6 months at room temperature. Importantly, improved SD dissolution was accompanied by higher UA activity against trypomastigote forms of Trypanosoma cruzi, but not against mammalian fibroblasts, enhancing the potential of UA for Chagas disease treatment.

Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy

“…FTIR analysis is a useful tool to investigate intermolecular interactions, through shift or broadening of the bands in the spectra [42,43]. In Fig.…”

“…It is important to note that RAP bands in the liposomes were more broadened, appearing at a higher temperature, suggesting that RAP was at least partially converted from the crystalline to the amorphous state in liposomes. An important consequence is that amorphous drugs are more soluble and thus could present enhanced bioavailability [43]. In some spectra in Fig.…”

Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics

“…Further, the different ratio of SA and Gelucire were optimized to obtain maximum entrapment, and drug loading with sustained release (SI Table 2). It is evident from the ratio of SA and gelucire (SI Table 2) that addition of gelucire led to an increased release of drug from nanoparticles as gelucire is [33] known for faster dissolution. When SLNs prepared with gelucire, release was estimated faster since in 16.8 hr more than 90 % drug was released, whereas slower release with SLNs prepared with SA was observed i.e.…”

“…SLNs-MTX was prepared using hot homogenization technique (Scheme 1) [33,34]. The high velocity stirring was employed to acquire a pre-emulsion phase.…”

Pharmacokinetics and Pharmacodynamics of the Triterpenoid Ursolic Acid in Regulating the Antioxidant, Anti-inflammatory, and Epigenetic Gene Responses in Rat Leukocytes

“…Thus, efforts have been made to develop UA derivatives with more favorable PK properties 34 . In addition, several studies have attempted to improve bioavailability by modifying the formulation of UA 4, 35, 36 . Nevertheless, we found that phase II anti-oxidant genes could still be slightly induced in leukocytes following an oral dose of 100 mg/kg UA (Figure 7).…”