ABSTRACT
Despite their incredible contribution to fighting viral infections, antiviral viral resistance is an increasing concern and often arises due to unfavorable physicochemical and biopharmaceutical properties. To address this kind of issue, lipid nanocapsules (LNC) are developed in this study, using efavirenz (EFV) as a drug model. EFV solubility was assessed in water, Labrafac Lipophile and medium chain triglycerides oil (MCT oil). EFV turned out to be more soluble in the two latter dissolving media (solubility > 250 mg/mL); hence, given its affordability, MCT oil was used for LNC formulation. LNC were prepared using a low-energy method named phase inversion, and following a design of experiments process. This one resulted in polynomial models that predicted LNC particle size, polydispersity index and zeta potential that were, respectively, around 50 nm, below 0.2 and below −33 mV, for the optimized formulations. Once synthesized, we were able to achieve an encapsulation efficacy of 87%. On the other hand, high EFV release from the LNC carrier was obtained in neutral medium as compared to acid milieu (pH 4) with, respectively, 42 and 27% EFV release within 74 h. Other characterization techniques were applied and further supported the successful encapsulation of EFV in LNCs in an amorphous form. Stability studies revealed that the developed LNC were quite stable over the period of 28 days. Ultimately, LNCs have been demonstrated to improve the biopharmaceutical properties of EFV and could therefore be used to fight against antiviral resistance.
ABSTRACT
Metallic nanoparticles (MNPs) produced by green synthesis using plant extracts have attracted huge interest in the scientific community due to their excellent antibacterial, antifungal and antibiofilm activities. To evaluate these pharmacological properties, several methods or protocols have been successfully developed and implemented. Although these protocols were mostly inspired by the guidelines from national and international regulatory bodies, they suffer from a glaring absence of standardization of the experimental conditions. This situation leads to a lack of reproducibility and comparability of data from different study settings. To minimize these problems, guidelines for the antimicrobial and antibiofilm evaluation of MNPs should be developed by specialists in the field. Being aware of the immensity of the workload and the efforts required to achieve this, we set out to undertake a meticulous literature review of different experimental protocols and laboratory conditions used for the antimicrobial and antibiofilm evaluation of MNPs that could be used as a basis for future guidelines. This review also brings together all the discrepancies resulting from the different experimental designs and emphasizes their impact on the biological activities as well as their interpretation. Finally, the paper proposes a general overview that requires extensive experimental investigations to set the stage for the future development of effective antimicrobial MNPs using green synthesis.
ABSTRACT
The present study aimed to develop a pH-sensitive chitosan-based hydrogel for controlled delivery of an anti-hepatitis B drug, tenofovir disoproxil fumarate (TDF). Free radical polymerization was utilized to graft acrylamide and acrylic acid using N,N-methylene bisacrylamide as the crosslinker. Physicochemical characterization confirmed the synthesis of thermally stable chitosan-g-poly(acrylamide-co-acrylic acid) hydrogels with well-defined pores within a fibrous surface. The prepared hydrogels exhibited pH and ionic strength sensitivity, with the swelling significantly lower under acidic and strong ionic strength conditions but higher in neutral and basic solutions. In addition, cytotoxicity studies on HeLa cell lines proved the cytocompatibility of the drug delivery material and its readiness for physiological applications. The encapsulation of TDF in the hydrogels was optimized and an encapsulation efficiency and a drug loading percentage of 96% and 10% were achieved, respectively. More interestingly, in vitro release studies demonstrated a pH-dependent release of TDF from hydrogels. The release at pH 7.4 was found to be up to five times higher than at pH 1.2 within 96 h. This further suggested that the newly developed hydrogel-loaded TDF could be proposed as a smart delivery system for oral delivery of anti-hepatitis B drugs.
