Chemical structure modifications and nano‐technology applications for improving ADME‐Tox properties, a review

Abstract

The chemical structure of a drug molecule affects its physicochemical properties and subsequent biological activities. Many pharmacologically active molecules fail to reach the market or have an inconvenient route of administration due to their chemical structure. This is especially important with the recent tendency to develop drug candidates beyond the drug-likeness space for addressing difficult targets such as protein-protein interfaces. The objective of this review is to discuss chemical and pharmaceutical approaches for circumventing structure-related problems and achieving acceptable ADME-Tox properties. The chemical structure-associated limitations are critically discussed. Chemical modifications and pharmaceutical technology applications for improving drug-likeness are illustrated. Attention is paid to modern therapeutic candidates and targets. In conclusion, chemical modifications as well as nanotechnology applications can be used effectively to enhance absorption, permeability, and selective distribution to a body compartment, to improve drug specificity, to limit off-target toxicity as well as to enhance stability and to protect against metabolism. The nano-technology-based solutions are relatively easier to develop over a new molecular entity, but adopting the chemical approach is more established in terms of safety, quality control, and regulatory assessment methods. K E Y W O R D Sblood-brain barrier, cancer tissue delivery, drug delivery, drug targeting, protein-protein interaction

Glucose-induced self-assembly and phase separation in hydrophilic triblock copolymers and the governing mechanism

“…7a presents Cur broad spectra with a noted absorbance maximum at B420 nm due to low-energy p-p* excitation, matching well with the reported work. 34,80 For the waterbased systems, the amounts of Cur absorbed in F38, F68, F88, F98, and F108 without glucose micelles are 0.9 mg mL À1 , 1.2 mg mL À1 , 1.6 mg mL À1 , 1.7 mg mL À1 and 1.9 mg mL À1 , respectively, which are more than the reported solubility value of Cur in water (0.6 mg mL À1 ). 27 This reflects the novelty of this work.…”

“…[84][85][86] Though poor water solubility and low absorption in the human body are major limitations facing Cur, recent research has demonstrated that the drawbacks of Cur can be effectively addressed when it is integrated into Pluronic sbased micellar nanocarriers. 80,86 Spectral studies of the examined system revealed an enhancement in the solubility of the waterinsoluble drug Cur in conjunction with the BCP micelles (Fig. 7).…”

“…42,78,79 The reason for selecting Cur in our study is due to its pharmacological and therapeutic properties, numerous medicinal benefits, and low degree of toxicity. [80][81][82][83] With these features, Cur is used in the prevention or therapy of cardiovascular disease, respiratory diseases, cancer, neurodegeneration, infection, and inflammation based on cellular biochemistry, physiological regulation, infection suppression, and immunomodulation. [84][85][86] Though poor water solubility and low absorption in the human body are major limitations facing Cur, recent research has demonstrated that the drawbacks of Cur can be effectively addressed when it is integrated into Pluronic sbased micellar nanocarriers.…”

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

“…In recent years, numerous drug delivery systems, including liposomes, micelles, “smart” polymers, and hydrogels, have been developed for cancer therapy [ 547 – 552 ]. For instance, to achieve accurate delivery to mitochondria with high specificity and low size, a native genetic system encoded in Salmonella pathogenicity island-1 (SPI-1) was used by Lim et al [ 553 ].…”

Curcuma Longa Herbs: A Mechanism to Increase the Innate Immune Response Through a Pharmacological System Approach

“…This is especially important given the recent trend to develop drug candidates out of space similar to drugs to deal with difficult target proteins due to the need for linkage between proteins. The aim of the in silico research is to conduct an accurate study with chemical and pharmaceutical approaches so that drug candidates are known to have good ADME-Tox properties and high bioavailability [11].…”