Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported.

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Gold nanoparticles (AuNPs) are produced for many applications but there is a lack of available data on their skin absorption. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. A physiological solution was used as receiving phase and 0.5 mL (1st exp) and 1.5 mL (2nd exp) of a solution containing 100 mgL and 7.1 ± 2.5 ng cm-2 h -1 in intact and damaged skin, respectively, with a lag time less than 1 hour. Transmission Electron Microscope analysis on skin samples and chemical analysis using Inductively Coupled PlasmaMass Spectrometry demonstrated the presence of AuNPs into epidermis and dermis. This study showed that AuNPs are able to penetrate the human skin in an in vitro diffusion cell system.

Herein is presented a rare example of salt/ cocrystal polymorphism involving the adduct between ethionamide (ETH) and salicylic acid (SAL). Both the salt and cocrystal forms have the same stoichiometry and composition and are both stable at room temperature. The synthetic procedure was successfully optimized in order to selectively obtain both polymorphs. The two adducts' structures were thoroughly investigated by means of singlecrystal X-ray diffraction, solid-state NMR spectroscopy, and density functional theory (DFT) calculations. From the solidstate NMR point of view, the combination of mono-and multinuclear experiments ( 1 H MAS, 13 C and 15 N CPMAS, 1 H-{ 14 N} D-HMQC, 1 H− 14 N PM-S-RESPDOR) provided undoubted spectroscopic evidence about the different positions of the hydrogen atom along the main N•••H•••O interaction. In particular, the 1 H− 14 N PM-S-RESPDOR allowed N−H distance measurements through the 1 H detected signal at a very high spinning speed (70 kHz), which remarkably agree with those derived by DFT optimized X-ray diffraction, even on a natural abundance real system. The thermodynamic relationship between the salt and the cocrystal was inquired from the experimental and computational points of view, enabling the characterization of the two polymorphs as enantiotropically related. The performances of the two forms in terms of dissolution rate are comparable to each other but significantly higher with respect to the pure ETH.

The order-disorder phase transition associated with the uprise of reorientational motion in (DABCOH2) , in the supramolecular salts of general formula [1⋅(DABCOH )]X (where 1=12-crown-4, DABCO=1,4-diazabicyclo[2.2.2]octane, and X=Cl or Br ), has been investigated by variable temperature X-ray diffraction on single crystals and powder samples, as well as by DSC and solid-state NMR spectroscopy (SSNMR). The two compounds undergo a reversible phase change at 292 and 290 K, respectively. The two crystalline materials form solid solutions [1⋅(DABCOH )]Cl Br in the whole composition range (0 < x<1), with a decrease in the temperature of transition to a minimum of ca 280 K, corresponding to x=0.5. Activation energy values for the dynamic processes, evaluated by variable-temperature C magic-angle spinning (MAS) SSNMR and line-shape analysis are ca. 50 kJ mol in all cases. Combined diffraction and spectroscopic evidence has allowed the detection of a novel dynamic process for the (DABCOH ) dications, based on a room temperature precessional motion that is frozen out below the disorder-order transition; to the best of the authors' knowledge this phenomenon has never been observed before.

The possibility of decreasing the solubility of the antidepressant drug venlafaxine hydrochloride by formation of molecular salts with organic acids accepted by the Pharmacopeia has been successfully investigated. Reacting venlafaxine with coumaric, ferulic, oxalic, salicylic, fumaric, and citric acids results in the protonation of the amino group and formation of the corresponding 1:1 molecular salts. All compounds have been characterized by a combination of solid state techniques, i.e., single crystal and powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy and solid-state NMR (1H MAS, 13C and 15N CPMAS, 1H DQ MAS, two-dimensional (2D) 13C–1H HETCOR, and 2D 14N–1H J-HMQC) spectroscopy. Intrinsic dissolution tests were performed on the pure salts, and suitable candidates were selected for the preparation of solid formulations with excipients; dissolution profiles for the solid formulations were measured in water and sodium chloride solution, and compared with that of the commercial form of venlafaxine, showing that the coumarate salt might represent an improvement for extended release administrations.

The formation of a codrug, a cocrystal formed by two active pharmaceutical ingredients (APIs), between theophylline (THEO) and pyridoxine·HCl (PyrH+Cl–) is reported. The THEO PyrH+Cl– drug–drug cocrystal could turn out to be interesting in the pharmaceutical field because these two APIs are concurrently administered for asthma treatment. The codrug was characterized by a combined experimental and computational investigation by means of single crystal X-ray diffraction (SCXRD), solid-state NMR (SSNMR), and density functional theory (DFT) calculations. An exhaustive SSNMR study was performed to unravel the complex network of hydrogen bond interactions which was poorly defined by SCXRD. Several advanced two-dimensional SSNMR spectra such as 1H DQ MAS, 13C–1H HETCOR, 14N–1H J- and D-HMQC were acquired, taking advantage of the resolution and sensitivity improvement provided by indirect detection pulse sequences and very fast MAS at 70 kHz. These experiments, supported and completed by DFT calculations, were fundamental in accurately determining the position of hydrogen atoms and thus in elucidating the hydrogen bond network. They also allowed defining the ionic character of the drug–drug cocrystal, which can be more properly defined as a drug–drug salt cocrystal.

The structures and solid-state dynamics of the supramolecular salts of the generalf ormula [(12-crown-4) 2 ·DABCOH 2 ](X) 2 (whereD ABCO = 1,4-diazabicyclo[2.2.2]octane, X = BF 4 ,C lO 4 )h ave been investigated as af unction of temperature (from 100 to 360 K) and pressure (up to 3.4 GPa), through the combination of variable-temperature and variable-pressure XRD techniques and variable-temperature solid-state NMR spectroscopy.T he two salts are isomorphous and crystallize in the enantiomeric space groups P3 2 2 1 and P3 1 2 1 .A ll building blocks composing the supramolecular complex display dynamic processes at ambient temperature and pressure. It has been demonstrated that the motion of the crown ethers is maintained on lowering the temperature (down to 100 K) or on increasing the pressure (up to 1.5 GPa) thankst ot he correlation between neighboring molecules, whichm esh and rotate in ac oncerted manner similar to spiralg ears. Above 1.55 GPa, ac ollapse-type transition to al ower-symmetry ordered structure, not attainable at at emperature of 100 K, takes place, proving, thus, that the pressure acts as the means to couple and decouple the gears. The relationship between temperature and pressure effects on molecular motion in the solid state has also been discussed.[a] Dr.