Modelling lethality and teratogenicity of zebrafish (Danio rerio) due to ß-lactam antibiotics employing the QSTR approach.

Nowadays, ß-lactam antibiotics are one of the most consumed OTC (over-the-counter) medicines in the world. Its frequent use against several infectious diseases leads to the development of antibiotic resistance. Another unavoidable risk factor of ß-lactam antibiotics is environmental toxicity. Numerous terrestrial as well as aquatic species have suffered due to the excessive use of these pharmaceuticals. In this present study, we have performed a toxicity assessment employing a novel in silico technique like quantitative structure-toxicity relationships (QSTRs) to explore toxicity against zebrafish (Danio rerio). We have developed single as well as inter-endpoint QSTR models for the ß-lactam compounds to explore important structural attributes responsible for their toxicity, employing median lethal (LC50) and median teratogenic concentration (TC50) as the endpoints. We have shown how an inter-endpoint model can extrapolate unavailable endpoint values with the help of other available endpoint values. To verify the models' robustness, predictivity, and goodness-of-fit, several universally popular metrics for both internal and external validation were extensively employed in model validation (single endpoint models: r2 = 0.631 - 0.75, Q2F1 = 0.607 - 0.684; inter-endpoint models: r2 = 0.768 - 0.84, Q2F1 = 0.678 - 0.76). Again, these models were engaged in the prediction of these two responses for a true external set of ß-lactam molecules without response values to prove the reproducibility of these models.

Recent Advances in the Use of Cubosomes as Drug Carriers with Special Emphasis on Topical Applications.

Topical drug delivery employing drug nanocarriers has shown prominent results in treating topical ailments, especially those confined to the skin and eyes. Conventional topical formulations persist with drug and disease-related challenges during treatment. Various nanotechnology-driven approaches have been adopted to mitigate the issues associated with conventional formulations. Among these, cubosomes have shown potential applications owing to their liquid crystalline structure, which aids in bioadhesion, retention, sustained release, and loading hydrophilic and hydrophobic moieties. The phase transition behavior of glyceryl monooleate, the concentration of stabilizers, and critical packing parameters are crucial parameters that affect the formation of cubosomes. Microfluidics-based approaches constitute a recent advance in technologies for generating stable cubosomes. This review covers the recent topical applications of cubosomes for treating skin (psoriasis, skin cancer, cutaneous candidiasis, acne, and alopecia) and eye (fungal keratitis, glaucoma, conjunctivitis, and uveitis) diseases. The article summarizes the manufacturing and biological challenges (skin and ocular barriers) that must be considered and encountered for successful clinical outcomes. The patented products are successful examples of technological advancements within cosmeceuticals that support various topical applications with cubosomes in the pharmaceutical field.