Enhanced bioavailability and anthelmintic efficacy of mebendazole in redispersible microparticles with low-substituted hydroxypropylcellulose

Abstract

BackgroundMebendazole (MBZ) is an extremely insoluble and therefore poorly absorbed drug and the variable clinical results may correlate with blood concentrations. The necessity of a prolonged high dose treatment of this drug increases the risk of adverse effects.MethodsIn the present study we prepared redispersible microparticles (RDM) containing MBZ, an oral, poorly water-soluble drug, in different proportions of low-substituted hydroxypropylcellulose (L-HPC). We investigated the microparticulate structures that emerge spontaneously upon dispersion of an RDM in aqueous medium and elucidated their influence on dissolution, and also on their oral bioavailability and therapeutic efficiency using a murine model of infection with the nematode parasite Trichinella spiralis.ResultsElevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s) under the curve (AUC)0-∞ values. Likewise, after oral administration of the RDM-1:2.5 and RDM-1:5 the AUC0-∞ were 2.67- and 2.97-fold higher, respectively, compared to those of pure MBZ. Therapeutic activity, assessed on the Trichinella spiralis life cycle, showed that RDM-1:5 was the most effective in reducing the number of parasites (4.56-fold) as compared to pure MBZ, on the encysted stage.ConclusionThe MBZ: L-HPC RDM might be an effective way of improving oral bioavailability and therapeutic activity using low doses of MBZ (5 mg/kg), which implies a low degree of toxicity for humans.

In Silico and In Vitro Studies for Benzimidazole Anthelmintics Repurposing as VEGFR-2 Antagonists: Novel Mebendazole-Loaded Mixed Micelles with Enhanced Dissolution and Anticancer Activity

“…High doses of MBZ cause anemia and liver damage. 36 Moreover, studies have shown evidence of teratogenic effects of MBZ in rats and mice. To overcome poor aqueous solubility and enhance the bioavailability of MBZ at a lower dose, MMs were prepared to contain a hydrophobic block that enables the poorly soluble drugs to be incorporated as an internal core and a hydrophilic block as a surrounding shell improving its activity.…”

Antihelminthic and antiangiogenic effects of zinc oxide nanoparticles on intestinal and muscular phases of trichinellosis

“…In addition to the growing resistance against these drugs, they have low water solubility, which restricts their absorption from the intestine and reduces their bioavailability (Khalikov 2021). Accordingly, they are utilized in large dosages with negative side effects (de la Torre-Iglesias et al 2014). As a result, there is an urgent requirement for new and safer medications, particularly those that are effective against larval stages of Trichinella , which can result in serious types of long-term inflammatory myositis and myopathy.…”

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

“…Efforts have mainly been done to develop new formulations to enhance the solubility and oral bioavailability of the drug. In this regard, micro-particles of hydroxypropylcellulose, a cellulose derivative polymer used for the preparation of artificial tears in the ophthalmic industry, has recently been used as a carrier of MBZ at low dose (5 mg·kg -1 ) [ 66 ]. This formulation proved significantly more active than pure MBZ against all the developmental stages of the nematode Trichinella spiralis in a murine model.…”