Enhanced Micro-Channeling System via Dissolving Microneedle to Improve Transdermal Serum Delivery for Various Clinical Skincare Treatments.

Topical liquid formulations, dissolving microneedles (DMNs), and microscale needles composed of biodegradable materials have been widely used for the transdermal delivery of active compounds for skincare. However, transdermal active compound delivery by topical liquid formulation application is inhibited by skin barriers, and the skincare efficacy of DMNs is restricted by the low encapsulation capacity and incomplete insertion. In this study, topical serum application via a dissolvable micro-channeling system (DMCS) was used to enhance serum delivery through micro-channels embedded with DMNs. Transdermal serum delivery was evaluated after the topical-serum-only application and combinatorial serum application by assessing the intensity of allophycocyanin (APC) loaded with the serum in the porcine skin. APC intensity was significantly higher in the skin layer at a depth of 120-270 µm upon combinatorial serum application as compared to topical-serum-only application. In addition, the combinatorial serum application showed significantly improved efficacy in the clinical assessment of skin hydration, depigmentation, improvement of wrinkles, elasticity, dermal density, skin pores, and skin soothing without any safety issues compared to the serum-only application. The results indicate that combinatorial serum application with DMCS is a promising candidate for improving skincare treatments with optimal transdermal delivery of active compounds.

Development of Lidocaine-Loaded Dissolving Microneedle for Rapid and Efficient Local Anesthesia.

Lidocaine is a local anesthetic agent used in the form of injection and topical cream. However, these formulation types have limitations of being either painful or slow-acting, thereby hindering effective and complete clinical performance of lidocaine. Dissolving microneedles (DMNs) are used to overcome these limitations owing to their fast onset time and minimally invasive administration methods. Using hyaluronic acid and lidocaine to produce the drug solution, a lidocaine HCl encapsulated DMN (Li-DMN) was fabricated by centrifugal lithography. The drug delivery rate and local anesthetic quality of Li-DMNs were evaluated using the pig cadaver insertion test and Von Frey behavior test. Results showed that Li-DMNs could deliver sufficient lidocaine for anesthesia that is required to be utilized for clinical level. Results from the von Frey test showed that the anesthetic effect of Li-DMNs was observed within 10 min after administration, thus confirming fast onset time. A toxicity test for appropriate clinical application standard was conducted with a microbial limit test and an animal skin irritation test, showing absence of skin irritation and irritation-related microorganisms. Overall, Li-DMN is a possible alternative drug delivery method for local anesthesia, meeting the requirements for clinical conditions and overcoming the drawbacks of other conventional lidocaine administration methods.

Synthesis and characterization of self-assembled nanoscopic metallarectangles capable of binding fullerenes with size-selective responses.

Two new metallarectangles, 4 and 5, were obtained from the self-assembly of areneruthenium-based molecular clips 2 and 3 with a new dipyridyl donor ligand 1 containing a diamide core and ethynyl spacers. The metallarectangles were characterized by multinuclear NMR, electrospray ionization mass spectrometry, and UV-vis spectroscopy, and the molecular structure of 4 was unambiguously determined by single-crystal X-ray diffraction analysis. Because of the presence of an extended π-electron aromatic surface, the tetracene-containing molecular rectangle 5 was capable of binding C60 and C70 fullerenes as quantified by UV-vis, emission, and (1)H NMR experiments, providing an example of a supramolecular host capable of recognizing large guest molecules.

Self-assembly of ambidentate pyridyl-carboxylate ligands with octahedral ruthenium metal centers: self-selection for a single-linkage isomer and anticancer-potency studies.

The synthesis of six new [2+2] metallarectangles through the coordination-driven self-assembly of octahedral Ru(II)-based acceptors with ambidentate pyridyl-carboxylate donors is described. These molecular rectangles are fully characterized by (1)H NMR spectroscopy, high-resolution electrospray mass spectrometry, and single-crystal X-ray diffraction. In each case, despite the possible formation of multiple isomers, based on the relative orientation of the pyridyl and carboxylate groups (head-to-head versus head-to-tail), evidence for the formation of a single preferred ensemble (head-to-tail) was found in the (1)H NMR spectra. Furthermore, the cytotoxicities of all of the rectangles were established against A549 (lung), AGS (gastric), HCT-15 (colon), and SK hep 1 (liver) human cancer cell lines. The cytotoxicities of rectangles that contained the 5,8-dihydroxy-1,4-naphthaquinonato bridging moiety between the Ru centers (9-11) were particularly high against AGS cancer cells, with IC50 values that were comparable to that of reference drug cisplatin.

Anticancer Activity of Self-Assembled Molecular Rectangles via Arene-Ruthenium Acceptors and a New Unsymmetrical Amide Ligand.

Two new and large molecular rectangles 4 and 5 were synthesized from two different arene-ruthenium [Ru(2)(µ-η(4)-C(2)O(4))(MeOH)(2)(η(6)-p-Pr(i)C(6)H(4)Me)(2)][O(3)SCF(3)](2) (2), and [Ru(2) (p-cymene)(2) (donq) (OH(2))(2)] [O(3)SCF(3)](2) (donq = 5,8-dioxydo-1,4-naphthaquinonato) (3) acceptors and a new unsymmetrical N-(4-(pyridin-4-ylethynyl)phenyl) isonicotinamide (1) donor ligand. X-ray crystallography of 4 confirmed a molecular rectangle. The (1)H NMR spectra of both rectangles 4 and 5 showed a mixture of two structural, head-to-tail (HTL) and head-to-head (HTH) type, isomers in a 1:1 ratio. The cytotoxicities of both rectangles have been established against Colo320 (colorectal cancer), A549 (lung cancer), MCF-7(breast cancer) and H1299 (lung cancer) human cancer cell lines. The cytotoxicity of rectangle 5 was found to be considerably stronger against all cancer cell lines than that of the reference drug cisplatin.

Self-assembled metalla-bowls for selective sensing of multi-carboxylate anions.

Two new tetranuclear cationic metalla-bowls 4 and 5 were self-assembled from a bis-pyridine amide ligand (H(2)L) (1) and arene-ruthenium acceptors, [(Ru(2)(µ-η(4)-C(2)O(4))(η(6)-p-cymene)(2)](O(3)SCF(3))(2) (2) and [Ru(2)(dhnd)(η(6)-p-cymene)(2)](O(3)SCF(3))(2) (dhnd = 6,11-dihydroxy-5,12-naphthacenedionato) (3), respectively. The metalla-bowls were characterized by multinuclear NMR, ESI-MS, UV-Vis spectroscopy, and single crystal X-ray diffraction study of 4. The crystal structure of 4 reveals unambiguous proof for the molecular shape of the metalla-bowl and the encapsulation of one triflate anion in the cavity through hydrogen bonding. The metalla-bowl 5 has been evaluated for anion binding studies by use of amide ligand as a hydrogen bond donor and arene-Ru acceptor as a signalling unit. UV-Vis titration studies showed that 5 selectively binds with multi-carboxylate anions such as oxalate, tartrate and citrate in a 1 : 1 fashion with high binding constants of 4.0-5.5 × 10(4) M(-1). Furthermore, the addition of multi-carboxylate anions into a solution of 5 gave rise to a large enhancement of fluorescence intensity attributable to the blocking of a photo-induced electron transfer process from the arene-ruthenium moiety to the amidic donor in 5. However, the fluorescence intensity almost remains unchanged upon addition of other anions including F(-), Cl(-), PF(6)(-), MeCOO(-), NO(3)(-) and PhCOO(-), as identically seen in the UV-Vis titration experiments, pointing to the high selectivity of 5 for the sensing of multi-carboxylate anions.