Synthesis of calix (4) resorcinarene based amphiphilic macrocycle as an efficient nanocarrier for Amphotericin-B to enhance its oral bioavailability.

The supramolecular-based macrocyclic amphiphiles have fascinating attention and find extensive utilization in the pharmaceutical industry for efficient drug delivery. In this study, we designed and synthesized a new supramolecular amphiphilic macrocycle to serve as an efficient nanocarrier, achieved by treating 4-hydroxybenzaldehyde with 1-bromotetradecane. The derivatized product was subsequently treated with resorcinol to cyclize, resulting in the formation of a calix(4)-resorcinarene-based supramolecular amphiphilic macrocycle. The synthesized macrocycle and intermediate products were characterized using mass spectrometry, IR, and 1H NMR spectroscopic techniques. The amphotericin-B (Amph-B)-loaded and unloaded amphiphiles were screened for biocompatibility studies, vesicle formation, particle shape, size, surface charge, drug entrapment, in-vitro release profile, and stability through atomic force microscopy (AFM), Zetasizer, HPLC, and FT-IR. Amph-B -loaded macrocycle-based niosomal vesicles were investigated for in-vivo bioavailability in rabbits. The synthesized macrocycle exhibited no cytotoxicity against normal mouse fibroblast cells and was found to be hemocompatible and safe in mice following an acute toxicity study. The drug-loaded macrocycle-based vesicles appeared spherical, nano-sized, and homogeneous in size, with a notable negative surface charge. The vesicles remained stable after 30 days of storage. The results of Amph-B oral bioavailability and pharmacokinetics revealed that the newly tailored niosomal formulation enhanced drug solubility, protected drug degradation at gastric pH, facilitated sustained drug release at the specific target site, and delayed plasma drug clearance. Incorporating such advanced niosomal formulations in the field of drug delivery systems has the potential to revolutionize therapeutic outcomes and improve the quality of patient well-being.

Classification of singular differential invariants in (1+3)-dimensional space and integrability.

Singularity is one of the important features in invariant structures in several physical phenomena reflected often in the associated invariant differential equations. The classification problem for singular differential invariants in (1+3)-dimensional space associated with Lie algebras of dimension 4 is investigated. The formulation of singular invariants for a Lie algebra of dimension 4 possessed by the underlying system of three second-order ordinary differential equations is studied in detail and the corresponding canonical forms for these systems are deduced. Furthermore, the categorization of singular invariants on the basis of conditional singularity, weak uncoupling, weak linearization, partial uncoupling and partial linearization are described for the underlying canonical forms. In addition, those cases of classified canonical forms are also mentioned which do not lead to singular invariant systems of three second-order ODEs for a Lie algebra of dimension 4. The integrability aspect of these classified singular-invariant systems in (1+3)-dimensional space is discussed in a detailed manner for a Lie algebra of dimension 4. Finally, two physical systems from mechanics are presented to illustrate the utilization of the physical aspect of these singular invariants.