Effects of drug-polymer dispersions on solubility and in vitro diffusion of artemisinin across a polydimethylsiloxane membrane

Abstract

Artemisinin (ART) is a sesquiterpene lactone with an endo-peroxide bridge that is thought to be responsible for its antimalarial activity. It has low oral bioavailability because of aqueous insolubility, which leads to local toxicity at the site of aggregation. The present work focused on increasing its solubility and evaluating its permeation across a model membrane to mimic transdermal delivery that bypasses the hepatic metabolism. For this purpose, physical mixtures (PM), solid dispersions (SD) and lyophilized dispersions (LD) with different drug-polymer ratios (1 : 0.5, 1 : 1, 1 : 2, 1 : 4 and 1 : 9) were prepared using the hydrophilic polymer polyvinylpyrrolidone (PVP). Drug-polymer dispersions were characterized using X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Solubility was measured in three solvents: de-ionized water, phosphate buffered saline (PBS) and methanol. The toluene-water partition coefficient was evaluated and compared with the literature and calculated logP values. In vitro diffusion of ART was studied across a polydimethylsiloxane membrane from a saturated solution of drug-polymer dispersions. XRD patterns showed a gradual decrease in crystallinity of ART with increasing polymer concentration, while FTIR confirmed no interactions between ART and PVP. Solubility was increased up to 4-, 5-and 8-fold for LD in water, PBS and methanol, respectively. The logP for toluene-water was 2.65 ± 0.3, which is in good agreement with literature and calculated logP values. Permeation was enhanced, which is attributed to the decrease in crystallinity and increase in wettability of the drug. The ART flux was significantly higher than that of pure ART (0.12 ± 0.01) with increasing PVP concentration for SD and LD formulations. In conclusion, drug-polymer dispersions with PVP improve the pharmaceutical properties of ART in the order LD>SD>PM.

Mn(ii) mediated degradation of artemisinin based on Fe3O4@MnSiO3-FA nanospheres for cancer therapy in vivo

“…For T 2 * -weighted MRI, a imaging sequence with repetition time (TR)/echo time (TE) = 1840/107.8 100 ms, number of excitations (NEX) = 2, echo train length = 20, 0.188 × 0.188 mm 2 in plane resolution with a slice thickness of 1 mm and 10 slices was carried out. Immunohistochemistry (IHC) staining Various organs and tumor tissues removed from the administrated 105 mice were fixed in 10% formalin, dehydrated with gradient ethanol, embedded in paraffin and sectioned. Then the organ sections were stained with hematoxylin and eosin (H&E) for the detection of changes in the cellular integrity and tissue morphology.…”

“…In order to illustrate that Mn 2+ could substitute for Fe 2+ to interact 105 with ART more efficiently and generate more free radicals, the catalytic degradation of ART by Fe 2+ and Mn 2+ was tested in the FeSO 4 and MnSO 4 solution separately with or without bicarbonate ions. As shown in Figure 3 a, the bicarbonate ions have little influence on the activity of Fe 2+ for ART 110 decomposition, and the degradation values of the two systems can both increase to above 22% after 22 h. On the contrary, the catalytic activity of Mn 2+ is really depended on bicarbonate ions.…”

Enhanced dissolution and stability of artemisinin by nano-confinement in ordered mesoporous SBA-15 particles

“…Furthermore, ART has become an alternative remedy recommended by the World Health Organization (WHO) since malaria parasites have developed resistances to the existing antimalarial drugs, such as chloroquine and quinine (Lapenna et al, 2009;Li and Zhou, 2010). ART poses several advantages compared to other anti-malarial drugs, such as low toxicity in a normal curative dose, high tolerance to patients, safe actions and high efficacy against malaria parasites as well as having a good intestinal permeability (Sahoo et al, 2010;Shahzad et al, 2012). However, ART suffers from poor water solubility (48 mg/L at 37 C) and short half life (2.5 h), which affects its bioavailability (32%).…”

“…However, ART suffers from poor water solubility (48 mg/L at 37 C) and short half life (2.5 h), which affects its bioavailability (32%). At the same time, the short half life and high first-pass metabolism of ART causes incomplete clearance of malaria parasites (Titulaer et al, 1990;Sahoo et al, 2011;Shahzad et al, 2012;Ferreira et al, 2013). Therefore, ART tablets need to be administered multiple times in order to provide sufficient concentration of ART to eliminate malaria parasites completely (Chen et al, 2009).…”

Surface wetting processing on BNNT films by selective plasma modes

“…BNNT films are promising composite polymer materials with enhanced toughness, designed for working in harsh environments. Even more, biology applications, such as drug delivery carried out by nanomaterials and biocompatible experiments, mainly ask for wettability change of BNNTs as well as fucnalizations [13][14][15][16][17][18]. Wettability changes do not usually affect other properties or destroy the structures of intact BNNTs.…”