Alginate‐Based Microcapsules with a Molecule Recognition Linker and Photosensitizer for the Combined Cancer Treatment

A reactive template method was used to fabricate alginate‐based hydrogel microcapsules. The uniform and well‐dispersed hydrogel capsules have a high drug loading capacity. After they are coated by a folate‐linked lipid mixture on the surface, the capsules possess higher cell uptake efficiency by the molecule recognition between folate and the folate‐receptor overexpressed by the cancer cells. Moreover, in this bioconjugate, the lipid could remarkably reduce the release rate of hydrophilic doxorubicin from the hydrogel microcapsules and encapsulate the hydrophobic photosensitizer hypocrellin B. The biointerfaced capsules could be used as drug carriers for combined treatment against cancer cell proliferation in vitro; this was much more effective than chemotherapy or photodynamic therapy alone.     

Trapped in Misbelief for Almost 40 Years: Selective Synthesis of the Four Stereoisomers of Mefloquine

Here we report the synthesis of all four stereoisomers of mefloquine. Mefloquine (Lariam) is an important anti‐malaria drug that is applied as a racemate of the erythro form. However, the (?)‐isomer induces psychosis, while the (+)‐enantiomer does not have this undesired side effect. There are six syntheses of which five lead to the wrong enantiomer without the authors of these syntheses noting that they had synthesized the wrong compound. At the same time physical chemistry investigations had assigned the absolute configuration correctly and the last enantioselective synthesis that took these results into account delivered the correct absolute configuration. Since various synthetic approaches failed to provide the correct stereoisomers in previous syntheses, we submit here a synthetic approach with a domino Sonogashira‐6π‐electrocyclisation as key step that confirmed synthetically the correct absolute configuration of all four isomers.     

Flexizyme‐Mediated Genetic Reprogramming As a Tool for Noncanonical Peptide Synthesis and Drug Discovery

Noncanonical peptides occur frequently in Nature, and often display high bioactivity. However, the lack of tractable systems for the synthesis of diverse libraries of such peptides has thus far hampered their development as drugs. Genetic reprogramming techniques, in which noncanonical amino acids may be incorporated into peptides, have largely removed this limitation. This Concept article outlines the development of these techniques with an emphasis on drug discovery.     

Recent Advances in Discovery of Lead Structures from Microbial Natural Products: Genomics- and Metabolomics-Guided Acceleration

Natural products (NPs) are evolutionarily optimized as drug-like molecules and remain the most consistently successful source of drugs and drug leads. They offer major opportunities for finding novel lead structures that are active against a broad spectrum of assay targets, particularly those from secondary metabolites of microbial origin. Due to traditional discovery approaches’ limitations relying on untargeted screening methods, there is a growing trend to employ unconventional secondary metabolomics techniques. Aided by the more in-depth understanding of different biosynthetic pathways and the technological advancement in analytical instrumentation, the development of new methodologies provides an alternative that can accelerate discoveries of new lead-structures of natural origin. This present mini-review briefly discusses selected examples regarding advancements in bioinformatics and genomics (focusing on genome mining and metagenomics approaches), as well as bioanalytics (mass-spectrometry) towards the microbial NPs-based drug discovery and development. The selected recent discoveries from 2015 to 2020 are featured herein.     

Fungal keratitis infected eye treatment with antibiotic-loaded zinc ions tagged polyvinyl acetate phthalate-g-polypyrrole drug carrier

Currently, the treatment of fungal keratitis (FK) infection remains a major clinical challenge, and current investigations, development in the field have widened approaches. The present work was aimed to synthesis a dual role novel carrier system consisting of Ofloxacin (OFL) and Nepafenac (NF) hydrophobic drugs incorporated in Zinc ions (Zn²⁺) tagged Polyvinyl acetate phthalate (PVAP) grafted Polypyrrole (PPy) carrier (OFL&NF-Zn²⁺/PVAP-g-PPy) to treat FK infection. The FT-IR, SEM, and dynamic light scattering revealed the carrier chemical structure, spherical shape, and the average particle size of 691.3 ± 1 nm. The carrier’s entrapment of OFL and NF drugs has been observed at 78.23% and 60.03%. The carrier exhibited significant antifungal activity at the concentration of 58 mg mL⁻¹ against Candida albicans which was lower than that of the free ofloxacin. The cell viability results suggested up to 70 μg/mL concentration of OFL&NF-Zn²⁺/PVAP-g-PPy did not induce any cytotoxicity on cultured ADSC cells at 48 h treatment time. It confirms the fact that the OFL&NF-Zn²⁺/PVAP-g-PPy carrier showed good biocompatibility and good anti-fungal activity. Thus the carriers provide a significant potential to improve the bioavailability of topically applied drugs to treat fungal eye infection.     

Thermal Stability of Amorphous Solid Dispersions

Amorphous solid dispersion drug delivery systems (ASD DDS) were proved to be efficient for the enhancement of solubility and bioavailability of poorly water-soluble drugs. One of the major keys for successful preparation of ASD is the selection of appropriate excipients, mostly polymers, which have a crucial role in improving drug solubility and its physical stability. Even though, excipients should be chemically inert, there is some evidence that polymers can affect the thermal stability of active pharmaceutical ingredients (API). The thermal stability of a drug is closely related to the shelf-life of pharmaceutical products and therefore it is a matter of high pharmaceutical relevance. An overview of thermal stability of amorphous solids is provided in this paper. Evaluation of thermal stability of amorphous solid dispersion is perceived from the physicochemical perspective, from a kinetic (motions) and thermodynamic (energy) point of view, focusing on activation energy and fragility, as well all other relevant parameters for ASD design, with a glance on computational kinetic analysis of solid-state decomposition.     

Multivalent Inhibitors for Carbohydrate‐Processing Enzymes: Beyond the “Lock‐and‐Key” Concept

During the last decades, tremendous chemical efforts have been dedicated to design monovalent inhibitors of carbohydrate‐processing enzymes, with comparatively few rewards in terms of marketed drugs. Recently, an alternative to the traditional “lock and key” approach has emerged. Multivalency, a widely used strategy for lectin inhibition, has been successfully applied to specific glycosidases and glycosyltransferases.     

Synthesis and aggregational behavior of acidic proteinoid

Polypeptide-based acidic proteinoid containing L -glutamic acid and L -aspartic acid in excess and five other neutral and basic amino acids in minor proportions have been synthesized and found that it forms organized aggregates in an aqueous solution. The proteinoid aggregate has been characterized using ¹³C-NMR, IR, and fluorescence spectroscopic techniques. The c.m.c. of the proteinoid has been determined by conductometric and pH metric methods. The aggregation studies were carried out at different temperatures and varying ionic strengths of the medium. The phase transition of the proteinoid aggregate has been determined using the fluorescence absorbance method. The aggregation behavior is shown to be dependent on the pH of the solution. This was also supported by conductivity measurements. Using methylene blue as a model drug, the drug delivery property of the proteinoid micelles were studied in acidic (pH 4.5) and neutral (pH 7.4) mediums. Using biphasic model thermochemical parameters, ΔG, ΔH, ΔS, and ΔC_p have been evaluated. © 1996 John Wiley & Sons, Inc.