Development of Chitosan/Cyclodextrin Nanospheres for Levofloxacin Ocular Delivery

Levofloxacin (LVF) is an antibacterial drug approved for the treatment of ocular infections. However, due to the low ocular bioavailability, high doses are needed, causing bacterial resistance. Polymeric nanospheres (NPs) loading antibiotic drugs represent the most promising approach to eradicate ocular infections and to treat pathogen resistance. In this study, we have developed chitosan NPs based on sulfobutyl-ether-β-cyclodextrin (CH/SBE-β-CD NPs) for ocular delivery of LVF. CH/SBE-β-CD NPs loading LVF were characterized in terms of encapsulation parameters, morphology, and sizes, in comparison to NPs produced without the macrocycle. Nuclear magnetic resonance and UV–vis spectroscopy studies demonstrated that SBE-β-CD is able to complex LVF and to influence encapsulation parameters of NPs, producing high encapsulation efficiency and LVF loading. The NPs were homogenous in size, with a hydrodynamic radius between 80 and 170 nm and positive zeta potential (ζ) values. This surface property could promote the interaction of NPs with the negatively charged ocular tissue, increasing their residence time and, consequently, LVF efficacy. In vitro, antibacterial activity against Gram-positive and Gram-negative bacteria showed a double higher activity of CH/SBE-β-CD NPs loading LVF compared to the free drug, suggesting that chitosan NPs based on SBE-β-CD could be a useful system for the treatment of ocular infections.

UV SPECTROSCOPY AND KINETIC RESEARCH OF PHOTODEGRADATION OF METHYL ORANGE IN THE PRESENCE OF TITANIUM DIOXIDE AND β-CYCLODEXTRIN OR ITS DERIVATIVES

The research is devoted to the study of the effect of β-cyclodextrin (β-CD) and its derivatives on the photocatalytic degradation of methyl orange in aqueous solutions in the presence of titanium dioxide. It has been shown that the kinetics of photodegradation of methyl orange is more accurately described by the pseudo first order equation for all investigated pH values. In the presence of cyclodextrins β-CD and 2-hydroxypropyl-β-cyclodextrin, acceleration of photodegradation was observed only after 30 min of irradiation. As a result, the oxidation of hydroxyl groups of cyclodextrin occurred. A significant slowdown in photodestruction in the TiO2-β-CD sample during the first 45 min is explained by the formation of inclusion complexes of cyclodextrin with methyl orange, which prevented the destruction of dye. The use of the β-cyclodextrin, its derivatives and increasing the acidity of the medium accelerates the processes of photodestruction of methyl orange in distilled and natural waters. Methyl orange was decolorized for 20 – 25 min in solutions of all investigated cyclodextrin derivatives at pH 2.5. The destruction of methyl orange was most effective with the use of sulfobutyl ether β-CD. The bactericidal lamp (λ = 254 nm) allows to increase the rate of destruction during the irradiation process. Methyl orange discolored much faster under the action of a bactericidal lamp than using only ultraviolet lamps with λ = 365 nm. A slight slowdown in the decomposition process is observed after several irradiation cycles. This may be due to the influence of the formed products of destruction. However, under such conditions, the by-products of reactions decompose much faster. The use of cyclodextrins is possible without significant loss of efficiency up to 8 cycles.

The Enantiomeric Discrimination of 5-Hexyl-2-methyl-3,4-dihydro-2H-pyrrole by Sulfobutyl ether-β-cyclodextrin: A Case Study

1-Pyrrolines are important intermediates of active natural products, such as the 2,5-dialkyl-1-pyrroline derivatives found in fire ant venoms. Here, 5-hexyl-2-methyl-3,4-dihydro-2H-pyrrole was synthesized by the enzymatic transamination/cyclization of 2,5-undecadione, and enantiodifferenciation was successfully achieved by capillary electrophoresis with sulfobutyl ether-β-cyclodextrin as the chiral selector. The rationale of the enantiomeric discrimination was based on the results of a docking simulation that revealed the higher affinity of (S)-5-hexyl-2-methyl-3,4-dihydro-2H-pyrrole for the sulfobutyl ether-β-cyclodextrin.

Inclusion Complex of Iloperidone with Sulfobutyl Ether Beta-Cyclodextrin: Characterization and Dissolution Studies

Iloperidone (ILO) is a second-generation antipsychotic drug and a first-line treatment approved by USFDA in May 2009. Iloperidone belongs to Biopharmaceutical Classification Systems (BCS) class II; thus, it is poorly water-soluble, highly permeable, and has pH-dependent solubility. Cyclodextrins and their derivatives have a wide range of applications in different formulations due to their complexation ability, which improves the solubility, stability, safety, and bioavailability of a drug. We have tried the complexation of iloperidone with sulfobutyl ether-β-cyclodextrin (SEβCD) to improve its solubility and dissolution. Complexation was done by the kneading method. The characterization of the SEβCD complexes with Iloperidone was done by FTIR, differential scanning calorimetry (DSC), saturation solubility, etc. A multimedia dissolution of the complex was carried out and compared with the plain drug. A significant improvement in drug release was found from SEβCD complexes in all media when compared with the drug alone.