Superstructure based on β-CD self-assembly induced by a small guest molecule

The size, shape and surface chemistry of nanoparticles play an important role in cellular interaction. Thus, the main objective of the present study was the determination of the β-cyclodextrin (β-CD) self-assembly thermodynamic parameters and its structure, aiming to use these assemblies as a possible controlled drug release system. Light scattering measurements led us to obtain the β-CD's critical aggregation concentration (cac) values, and consequently the thermodynamic parameters of the β-CD spontaneous self-assembly in aqueous solution: Δ[subscript agg]G[superscript o] = −16.31 kJ mol[superscript −1], Δ[subscript agg]H[superscript o] = −26.48 kJ mol[superscript −1] and TΔ[subscript agg]S[superscript o] = −10.53 kJ mol[superscript −1] at 298.15 K. Size distribution of the self-assembled nanoparticles below and above cac was 1.5 nm and 60–120 nm, respectively. The number of β-CD molecules per cluster and the second virial coefficient were identified through Debye's plot and molecular dynamic simulations proposed the three-fold assembly for this system below cac. Ampicillin (AMP) was used as a drug model in order to investigate the key role of the guest molecule in the self-assembly process and the β-CD:AMP supramolecular system was studied in solution, aiming to determine the structure of the supramolecular aggregate. Results obtained in solution indicated that the β-CD's cac was not affected by adding AMP. Moreover, different complex stoichiometries were identified by nuclear magnetic resonance and isothermal titration calorimetry experiments.Brazil. National Institute in Science and Technology in Nanobiopharmaceutics (NanoBiofar) (CNPq/MCT/FAPEMIG)Conselho Nacional de Pesquisas (Brazil)National Institutes of Health (U.S.) (Grant 1-R01-DE016516-03)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Process 4597-08-7)Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (CEX APQ-00498/08

Theoretical and experimental study of inclusion complexes formed by isoniazid and modified β-Cyclodextrins: 1H NMR structural determination and antibacterial activity evaluation

Me-β-cyclodextrin (Me-βCD) and HP-β-cyclodextrin (HP-βCD) inclusion complexes with isoniazid (INH) were prepared with the aim of modulating the physicochemical and biopharmaceutical properties of the guest molecule, a well-known antibuberculosis drug. The architectures of the complexes were initially proposed according to NMR data Job plot and ROESY followed by density functional theory (DFT) calculations of (1)H NMR spectra using the PBE1PBE functional and 6-31G(d,p) basis set, including the water solvent effect with the polarizable continuum model (PCM), for various inclusion modes, providing support for the experimental proposal. An analysis of the (1)H NMR chemical shift values for the isoniazid (H6',8' and H5',9') and cyclodextrins (H3,5) C(1)H hydrogens, which are known to be very adequately described by the DFT methodology, revealed them to be extremely useful, promptly confirming the inclusion complex formation. An included mode which describes Me-βCD partially enclosing the hydrazide group of the INH is predicted as the most favorable supramolecular structure that can be used to explain the physicochemical properties of the encapsulated drug. Antibacterial activity was also evaluated, and the results indicated the inclusion complexes are a potential strategy for tuberculosis treatment