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Lipophilic derivatives of the anticancer drug paclitaxel (PTX) were prepared by means of its conjugation to lipoamino acid (LAA) residues, with the aim of increasing drug accumulation in tumor cells. PTX was linked to the methyl esters of norleucine (C6) or 2-aminodecanoic acid (C10). A succinic acid group was used as a spacer to link the 2-hydroxyl group of PTX and the LAA residue, respectively by means of an ester and an amide bond. The in vitro anticancer activity of the prodrugs was tested on a human thyroid anaplastic cancer cell line (ARO). The intracellular uptake kinetics of free PTX and its prodrugs was assessed by HPLC. PTX-LAA prodrugs showed a noticeable cytotoxic activity against ARO cells at shorter incubation time (12 h) and lower doses (0.01-0.1 M) than PTX. Intracellular accumulation experiments indicated an improvement of drug concentration inside these cells, related to the block of the cellular expulsion by means of multi drug resistance efflux complex and improved physicochemical features that allowed the greater passive cellular membrane permeation. The enhanced activity of PTX-LAA prodrugs, in terms of potency and onset of the effect, as well as the interesting intracellular accumulation data suggest that these compounds can be further tested as possible alternatives to PTX for the treatment of resistant cancer cells.

Background: Retinoids represent an old class of bioactives used in the treatment of different skin pathologies (such as acne and psoriasis) and in the treatment of many tumors. Unfortunately, they present several side effects, i.e., burning of skin and general malaise after systemic administration and they are very unstable after exposition to light. Methods: One of the most promising new approaches for reducing the side effects of retinoids while improving their pharmacological effect is the use of drug-delivery devices. This review explains the current status of retinoid drug transport, which has been developing over the last few years, explaining the modification of their biopharmaceutical properties in detail after encapsulation/inclusion in vesicular and polymeric systems. Results/conclusion: Different colloidal and micellar systems containing retinoid drugs have been realized furnishing important potential advancements in traditional therapy.

The structure−activity relationship studies on 2-quinolinecarboxamide peripheral benzodiazepine receptor (PBR) ligands have been refined with the aim of using these ligands as carriers of radionuclides and boron atoms. Some new ligands show enhanced affinity and steroidogenic activity with respect to reference compound 1 and are interesting candidates for radiolabeling and PET studies. Moreover, carborane derivative 3q, representing the first example of PBR ligand bearing a carborane cage, can be useful to explore an alternative mechanism in BNCT.

The effects of different concentrations of β-cyclodextrin (β-CyD), hydroxypropyl-β-cyclodextrin (HP-β-CyD) and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CyD) on percutaneous absorption of papaverine hydrochloride (PAP) were investigated. Abdominal rat skin mounted in Franz cells was used for in vitroexperiments. To evaluate CyD interaction with a bilayer structure model, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and DPPC-Chol (8:2 mole ratio) vesicles were used. CyD vesicle interaction was evaluated by differential scanning calorimetry. Permeation through rat skin and calorimetric experiments demonstrated that at low concentrations DM-β-CyD shows higher enhancer activity as a possible result of a perturbing action on the skin by a complexation of its lipid components, but at higher concentrations HP-β-CyD is the most effective. By considering that HP-β-CyD presents a very moderate destabilizing action on the skin, we conclude that a 10 aqueous solution of this macrocycle appears to be the most suitable transdermal absorption enhancer for PAP.

We report the simultaneous determination of aspirin and its hydrolysis product, salicylic acid, in solid phase by fluorescence spectrophotometry. Aspirin is often the most labile component in a combination‐type analgesic compound. Therefore, its stability is often the initial concern in any formulation‐screening program. Preliminary screening of a large number of potential formulations can be arduous, because most current methods of analysis generally consist of several steps: extractions or column separations followed by UV, colorimetric, or gas‐liquid chromatographic assays. The method proposed here is quite suited to large numbers of assays because it is not time consuming, it is straightforward, and it is not subject to interference from the substances present in the pharmaceutical formulations. In addition, the method is nondestructive, not dependent on the sampling procedure, and, above all, quite sensitive.

We report the encapsulation of neutrase in liposornes for the acceleration of cheese ripening. The liposome preparation procedure consisted of repeated freeze-thaw cycles of multilarnellar vesicles followed by extrusion through polycarbonate filters. The neutrase encapsulation efficiency in the liposomes was influenced by the number of freeze-thaw cycles, achieving the highest value after seven cycles. Filtration through 200-nm polycarbonate membranes yielded homogenous size liposome populations with trapping efficiencies of about 65%. The vesicle stability and low neutrase release during the first stages of the cheese-making procedure, coupled with an almost quantitative retention of neutrase-loaded liposomes in cheese curd, ensured a proteolysis rate that was twice that observed in the control cheese.

Some physicochemical behaviours were investigated of polyethyl- (PECA) and polyisobutylcyanoacrylate (PICA), which, in recent years, have been proposed as nanoparticle colloidal systems for drug carrying. We observed the influence of preparation conditions, such as pH value and surfactant concentration, on parameters such as particle size and polymer molecular weight. Lower operating pH values (0-2) resulted in smaller nanoparticles than those prepared at pH 5·5. The polymer molecular weight was also a function of pH: low molecular weight at low pH and vice-versa. The surfactant concentration positively influenced main particle size and polymer molecular weight. These trends were independent of type of monomer; in fact, both ethyl- (ECA) and isobutyl-2-cyanoacrylate (ICA) showed the same behaviour. Loading capacity, as well as release profile, of the two polymers were evaluated using fluorescein as a model drug. Whereas both polymers showed almost the same release profile, there was a difference in the amount of encapsulated probe: higher aliquots for PICA than for PECA. Storage effects on such physicochemical parameters were also tested.

The inclusion properties of modifiedß-cyclodextrins (trimethyl-ß-cyclodextrin, dimethyl-ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) towards idebenone were compared with naturalß-cyclodextrin. The inclusion complexes were prepared by different methods (coprecipitation, kneading, and freeze-drying) and characterized by differential scanning calorimetry, X-ray diffractometry, UV, CD and NMR spectroscopy. The results obtained by CD and NMR spectroscopy indicate a different orientation of idebenone in dimethyl-ß-cyclodextrin with respect to other cyclodextrins. Stability constants of the complexes were determined in water at various temperatures and consequently thermodynamic parameters were obtained. All cyclodextrins are able to significantly increase the water solubility of idebenone, particularly dimethyl-ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin, as a result of complexation. Consequently, they enhance the dissolution rate of the complexed drug compared to the free drug.

The release of fluorescein from polyethylcyanoacrylate (PECA) or polyisobutylcyanoacrylate (PICA) nanoparticles was affected by the surfactants used for the preparation. The different surfactants also modified the molecular weight, size and loading of the nanoparticles. However, these factors were not be responsible for the different release. According to the release profiles and the Baker-Lonsdale model, a portion of fluorescein was concentrated near the nanoparticle surface. Thus, a non-homogeneous distribution of the fluorescent probe inside the nanoparticles was hypothesized. This distribution could reflect the fluorescein position inside the micella during the polymerization stage, or could be reached during the washing stage as the consequence of a different effect of the surfactants on the porosity of the nanoparticle structure.

In this work it was reported the determination of CDP-choline entrapment efficiency in MLVs liposomes constituted of neutral or negatively charged phospholipids. The encapsulation capacity (EC) increases with using charged phospholipids; moreover, also the presence of cholesterol into the vesicle bilayers enhances the EC values, Liposomes, prepared with reverse - -phase evaporation method, entrapped greater amounts of drug than multilamellar liposomes of the same composition, The size of liposomes so like as the polidispersity index values were determined by light scattering analysis;. The rate of CDP-choline efflux from liposomes was determined "in vitro" and was dependent upon bilayer composition and the method of preparation.

Dipalmitoylphosphatidylcholine (DPPC) liposomes were employed as membrane models for the investigation of the interaction occurring between methotrexate (MTX) and bilayer lipid matrix. Liposomes were obtained by hydrating a lipid film with 50 mM Tris buffer (pH7.4). The differential scanning calorimetry (DSC) evaluation of the thermotropic parameters associated with the phase transitions of DPPC liposomes gave useful information about the kind of drug-membrane interaction. The results showed an electrostatic interaction taking place with the negatively charged molecules of MTX and the phosphorylcholine head groups, constituting the outer part of DPPC bilayers. No interaction with the hydrophobic phospholipid bilayer domains was detected, revealing a poor capability of MTX to cross through lipid membranes to reach the interior compartment of a lipid bounded structure. These findings correlate well within vitrobiological experiments on MTX cell susceptibility.

Dipalmitoylphosphatidylcholine vesicles were used as a biological membrane model to investigate the interaction and the permeation properties of trimethoprim and brodimoprim as a function of drug protonation. The drug-membrane interaction was studied by differential scanning calorimetry. Both drugs interacted with the hydrophilic phospholipid head groups when in a protonated form. An experiment on the permeation of the two drugs through dipalmitoylphosphatidylcholine biomembranes showed higher diffusion rate constants when the two drugs were in the uncharged form; lowering of the pH (formation of protonated species) caused a reduction of permeation. Drug uptake by human neutrophil cells was also investigated. Both drugs may accumulate within neutrophils; however, brodimoprim does so to a greater extent. This accumulation is probably due to a pH gradient driving force, which allows the two drugs to move easily from the extracellular medium (pH approximately 7.3) into the internal cell compartments (acid pH). Once protonated, both drugs are less able to permeate and can be trapped by the neutrophils. This investigation showed the importance of the physicochemical properties of brodimoprim and trimethoprim in determining drug accumulation and membrane permeation pathways.

In order to incorporate ofloxacin within liposomes, the reverse-phase evaporation technique was carried out. The liposome lipid matrix consisted of dipalmitoylphosphatidylcholine-cholesterol-dihexadecylphosphate (4: 3:4 molar ratio). The liposome formulation presented a mean size of 185 +/- 31 nm and had an encapsulation capacity of 5.3 microliters/mumol. The liposome formulation was able to deliver ofloxacin into McCoy cells in a greater amount (2.6-fold) than the free drug, improving antibiotic accumulation.