ABSTRACT
The formulation of niosomes is influenced by a number of variables, and these variables may eventually affect the formulation's outcome. One of the elements that can influence the physico-chemical properties of niosomes is the method used in preparation of the formulation. In this study, we established if various methods of preparation have any impact on the prepared vesicles when loaded with 5-fluorouracil. Thereafter, a real-time cell assay (an in vitro cytotoxicity test) against HCT-116 colon cancer cell lines was done on an optimised batch. 5-fluorouracil loaded niosomes were prepared with either Tween 60 or Span 60 by four different methods - namely thin film hydration (TFH), reverse phase evaporation (RPE), evaporation/sonication (EVP/SON), and the ethanol injection method (EIM). In vitro evaluations were done on the formulations, and these included particle size analysis, entrapment efficiency, scanning electron microscopy (SEM), photomicrography, drug release, polydispersity index, and Fourier transform infrared spectroscopy (FTIR). The effects of the preparation method and type of non-ionic surfactants on encapsulation efficiency, particle size, and in vitro drug release of the niosomes at pH 7.4 were evaluated. An in vitro cytotoxicity test (real time cell assay (RTCA)) against HCT-116 cells was carried out using the optimised formulation. Results showed physically stable formulations. The TFH method produced the smallest particle sizes (187 nm and 482 nm), while the EVP/SON method produced the largest particle sizes (4476 nm and 9111 nm). The Tween-based niosomes prepared by TFH or RPE had higher drug entrapment. The FTIR studies of niosomal formulations showed broad peaks at wavenumbers above 3000 cm-1, indicating strong hydrogen bonds. The RTCA showed 5-fluorouracil-loaded niosomes caused more sustained cell death compared to the pure drug and blank niosomes. The methods of preparation affected the particle size, polydispersity index, entrapment efficiency, and the physical stability of the vesicles. The thin film hydration method was more robust in the entrapped 5-fluorouracil and showed lower particle sizes when compared to all the other methods. RTCA showed sustained cell death in real time.
ABSTRACT
The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether-lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol® ATO 5/Transcutol® HP and tallow fat/Transcutol® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol® ATO 5/Transcutol® HP batch, then 81% and 95% for tallow fat/Transcutol® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol® ATO 5/Transcutol® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference (P<0.05) in parasite reduction between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg), for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms.
