Current Topics in Medicinal Chemistry - Volume 21, Issue 2, 2021

Lipid nanoparticles (LNPs) have been widely applied in drug and gene delivery. More than twenty years ago, Doxil^TM was the first LNPs-based drug approved by the US Food and Drug Administration (FDA). Since then, with decades of research and development, more and more LNP-based therapeutics have been used to treat diverse diseases, which often offer the benefits of reduced toxicity and/or enhanced efficacy compared to the active ingredients alone. Here, we provide a review of recent advances in the development of efficient and robust LNPs for drug/gene delivery. We emphasize the importance of rationally combining experimental and computational approaches, especially those providing multiscale structural and functional information of LNPs, to the design of novel and powerful LNP-based delivery systems.

In this review, nanoscale-based drug delivery systems, particularly in relevance to the antiglaucoma drugs, have been discussed. In addition to that, the latest computational/in silico advances in this field are examined in brief. Using nanoscale materials for drug delivery is an ideal option to target tumours, and the drug can be released in areas of the body where traditional drugs may fail to act. Nanoparticles, polymeric nanomaterials, single-wall carbon nanotubes (SWCNTs), quantum dots (QDs), liposomes and graphene are the most important nanomaterials used for drug delivery. Ocular drug delivery is one of the most common and difficult tasks faced by pharmaceutical scientists because of many challenges like circumventing the blood-retinal barrier, corneal epithelium and the blood-aqueous barrier. Authors found compelling empirical evidence of scientists relying on in-silico approaches to develop novel drugs and drug delivery systems for treating glaucoma. This review in nanoscale drug delivery systems will help us understand the existing queries and evidence gaps and will pave the way for the effective design of novel ocular drug delivery systems.

Hyaluronan (HA) is a natural linear polysaccharide that has excellent hydrophilicity, biocompatibility, biodegradability, and low immunogenicity, making it one of the most attractive biopolymers used for biomedical researches and applications. Due to the multiple functional sites on HA and its intrinsic affinity for CD44, a receptor highly expressed on various cancer cells, HA has been widely engineered to construct different drug-loading nanoparticles (NPs) for CD44-targeted anti-tumor therapy. When a cocktail of drugs is co-loaded in HA NP, a multifunctional nano-carriers could be obtained, which features as a highly effective and self-targeting strategy to combat cancers with CD44 overexpression. The HA-based multidrug nano-carriers can be a combination of different drugs, various therapeutic modalities, or the integration of therapy and diagnostics (theranostics). Up to now, there are many types of HA-based multidrug nano-carriers constructed by different formulation strategies, including drug co-conjugates, micelles, nano-gels and hybrid NP of HA and so on. This multidrug nano-carrier takes the full advantages of HA as an NP matrix, drug carriers and targeting ligand, representing a simplified and biocompatible platform to realize the targeted and synergistic combination therapy against the cancers. In this review, recent progress of HA-based multidrug nano-carriers for combination cancer therapy is summarized and the potential challenges for translational applications have been discussed.

Aims: The present work aimed to develop MT loaded solid Nano dispersion by improving its solubility, half-life and bioavailability in biological system thereby this formulation may be afforded economically. Background: Small cell lung carcinoma is a type of malignant tumor characterized by uncontrolled cell growth at lung tissues. The potent anti-cancer drug methotrexate (MT) chosen for the present work is poorly soluble in water (BCS type IV class) with short half-life and hepatotoxic effect. Objective: With the concept of polymeric surfactant to improve the solubility along with wettability of drugs, the present work has been hypothesized to improve its solubility using polyvinyl pyrollidone (PVP K30) polymer and α- tocopheryl polyethylene glycol 1000 succinate (TPGS) surfactant, thereby the bioavailability is expected to get enhanced. By varying the PVP K30 and TPGS ratios different formulations were developed using emulsification process. Methods: The developed MT loaded solid nanodispersion was further characterized for its particle size, charge, morphology, encapsulation efficiency and in-vitro release behavior etc. Results: The results of FT-IR spectrometric analysis indicated the compatibility nature of MTX, PVPK30 and TPGS. The developed formulations showed spherical morphology, particle size ranging from 59.28±24.2 nm to 169.33±10.85 nm with a surface charge ranging from -10.33 ± 2.81mV to -9.57 ± 1.2 mV. The in vitro release studies as performed by dialysis bag method showed a sustained release pattern as checked by UV Spectrophotometer. Residual solvent analysis for MTXNDs performed by HPLC indicates there is no residual DMSO in the formulation. Transmission electron microscopic image of MTXNDs revealed that the particles are spherical shaped with a solid core structure. Haemolytic assay indicates that the developed formulation is safe for intravenous administration. Cell culture studies in A549 cells indicates the enhanced cytotoxic effect for the developed formulation. Conclusion: This proof of study indicates that the developed formulation may have anticancer potential for SCLC treatment.

Alzheimer's Disease (AD) is a devastating neurodegenerative disease that affects millions of people in the world. The abnormal aggregation of amyloid β protein (Aβ) is regarded as the key event in AD onset. Meanwhile, the Aβ oligomers are believed to be the most toxic species of Aβ. Recent studies show that the Aβ dimers, which are the smallest form of Aβ oligomers, also have the neurotoxicity in the absence of other oligomers in physiological conditions. In this review, we focus on the pathogenesis, structure and potential therapeutic molecules against small Aβ oligomers, as well as the nanoparticles (NPs) in the treatment of AD. In this review, we firstly focus on the pathogenic mechanism of Aβ oligomers, especially the Aβ dimers. The toxicity of Aβ dimer or oligomers, which attributes to the interactions with various receptors and the disruption of membrane or intracellular environments, were introduced. Then the structure properties of Aβ dimers and oligomers are summarized. Although some structural information such as the secondary structure content is characterized by experimental technologies, detailed structures are still absent. Following that, the small molecules targeting Aβ dimers or oligomers are collected; nevertheless, all of these ligands have failed to come into the market due to the rising controversy of the Aβ-related “amyloid cascade hypothesis”. At last, the recent progress about the nanoparticles as the potential drugs or the drug delivery for the Aβ oligomers are present.