Design and Characterization of Elastic Artificial Skin Containing Adenosine-Loaded Solid Lipid Nanoparticles for Treating Wrinkles.

Adenosine (AD), which is used for treating wrinkles, exhibits poor skin permeation. The aim of the present study was to develop a cross-linked silicone-based cellulose elastomer as an elastic artificial skin for the treatment of skin wrinkles, a biocompatible lipid-based nano-carrier for enhancing the skin permeation of AD, and a formulation consisting of the lipid-based carrier incorporated in the elastic artificial skin. AD-loaded solid lipid nanoparticles (SLNs) were prepared using a double-emulsion method. Particle characteristics and mechanical properties of SLNs and elastic artificial skin, respectively, were assessed. Skin permeation was evaluated using SkinEthic RHE tissue, a reconstructed human epidermis model. The mean particle size and zeta potential for SLNs ranged from 123.57 to 248.90 nm and -13.23 to -41.23 mV, respectively. The components of neither SLNs nor the elastic artificial skin were cytotoxic, according to cell- and tissue-viability assays and EU classification. SLNs and the elastic artificial skin exhibited sustained drug release for 48 h. The amount of AD released from SLNs and elastic artificial skin was approximately 10 times and 5 times higher, respectively, than that from AD solution. Therefore, elastic artificial skin incorporated with AD-loaded SLNs may serve as a promising topical delivery system for cosmeceutical treatment of skin wrinkles.

Dual Stimuli-Triggered Nanogels in Response to Temperature and pH Changes for Controlled Drug Release.

Poly-N-isopropyl acrylamide (PNIPAM) nanogels have been modified with different acrylic acid (AAc) contents for the efficient control of lower critical solution temperature (LCST). In this study, PNIPAM-co-AAc nanogels nanogels showed two volume phase transitions in comparison with PNIPAM. The transition temperature of PNIPAM nanogels was increased with AAc contents. The controlled drug release performance of PNIPAM-co-AAc nanogels loaded with ß-lapachone was attributed to the AAc content ratio and was efficiently triggered in response to temperature and pH. Moreover, a colorimetric cell proliferation assay and direct fluorescence-based live/dead staining were used to confirm the concurrence on drug release profiles. Finally, PNIPAM-co-AAc20 showed a relatively low level of drug release in the range of acidic to neutral pH at body temperature, while maximizing drug release at basic pH. Therefore, we demonstrated that the PNIPAM-based nanogel with the temperature- and pH-responsive features could be a promising nanocarrier for potential intestine-specific drug delivery.

Cell-Penetrating Peptide-Patchy Deformable Polymeric Nanovehicles with Enhanced Cellular Uptake and Transdermal Delivery.

We herein propose a polymeric nanovehicle system that has the ability to remarkably improve cellular uptake and transdermal delivery. Cell-penetrating peptide-patchy deformable polymeric nanovehicles were fabricated by tailored coassembly of amphiphilic poly(ethylene oxide)- block-poly(ε-caprolactone) (PEO- b-PCL), mannosylerythritol lipid (MEL), and YGRKKRRQRRR-cysteamine (TAT)-linked MEL. Using X-ray diffraction, differential scanning calorimetry, and nuclear magnetic resonance analyses, we revealed that the incorporation of MEL having an asymmetric alkyl chain configuration was responsible for the deformable phase property of the vehicles. We also discovered that the nanovehicles were mutually attracted, exhibiting a gel-like fluid characteristic due to the dipole-dipole interaction between the hydroxyl group of MEL and the methoxy group of PEO- b-PCL. Coassembly of TAT-linked MEL with the deformable nanovehicles significantly enhanced cellular uptake due to macropinocytosis and caveolae-/lipid raft-mediated endocytosis. Furthermore, the in vivo skin penetration test revealed that our TAT-patchy deformable nanovehicles remarkably improved transdermal delivery efficiency.

Polymeric vehicles for topical delivery and related analytical methods.

Recently a variety of polymeric vehicles, such as micelles, nanoparticles, and polymersomes, have been explored and some of them are clinically used to deliver therapeutic drugs through skin. In topical delivery, the polymeric vehicles as drug carrier should guarantee non-toxicity, long-term stability, and permeation efficacy for drugs, etc. For the development of the successful topical delivery system, it is of importance to develop the polymeric vehicles of well-defined intrinsic properties, such as molecular weights, HLB, chemical composition, topology, specific ligand conjugation and to investigate the effects of the properties on drug permeation behavior. In addition, the role of polymeric vehicles must be elucidated in in vitro and in vivo analyses. This article describes some important features of polymeric vehicles and corresponding analytical methods in topical delivery even though the application span of polymers has been truly broad in the pharmaceutical fields.

Topical delivery of retinol emulsions co-stabilised by PEO-PCL-PEO triblock copolymers: effect of PCL block length.

This article describes enhanced skin permeation and UV/thermal stability of retinol emulsions by the co-stabilisation of Tween20 and biodegradable poly(ethylene oxide)-block-poly(ε-caprolactone)-block-poly(ethylene oxide) (PEO-PCL-PEO) triblock copolymers having different lengths of hydrophobic PCL block. A triblock copolymer with a longer PCL block has a lower hydrophile-lipophile balance (HLB) value. Commercial Retinol 50C® (BASF Co., Ludwigshafen, Germany) was used as the source of retinol. Ultrasonication of the Retinol 50C® emulsion with the triblock copolymers led to an increase in retinol solubilisation and a decrease in average particle size of the resulting retinol emulsion. These characteristics improved skin permeation of retinol through the stratum corneum of artificial skin and subsequent proliferation of viable epidermis cell. Employment of the triblock copolymer with a longer PCL block increased both UV and thermal stabilization of the retinol. These results suggest that HLB and PCL block length are important factors to enhance the topical delivery of retinol into the skin.

Synthesis and characterization of PEO-PCL-PEO triblock copolymers: effects of the PCL chain length on the physical property of W(1)/O/W(2) multiple emulsions.

A series of poly(ethylene glycol)-block-poly(epsilon-caprolactone)-block-poly(ethylene glycol) (PEO-PCL-PEO) triblock copolymers were prepared and then used for the investigation of the effects of the ratio of epsilon-caprolactone to poly(ethylene glycol) (i.e., [CL]/[EO]) on the physical properties of water-in-oil-in-water (W(1)/O/W(2)) multiple emulsions containing a model reagent, ascorbic acid-2-glucoside (AA2G). In the synthesis, the [CL]/[EO] was varied from 0.11 to 0.31. The molecular weights and compositions of PEO-PCL-PEO were determined by GPC and (1)H NMR analyses. Thermal behavior and crystal formation were studied by DSC, XRD, FT-IR, and polarized optical microscopy (POM). Aggregate behavior of PEO-PCL-PEO was confirmed by DLS, UV, and (1)H NMR. Morphology and relative stiffness of the W(1)/O/W(2) multiple emulsions in the presence of PEO-PCL-PEO were studied by confocal laser scanning microscopy (CLSM) and rheometer. Variation in the [CL]/[EO] significantly affects the crystalline temperature and spherulite morphology of PEO-PCL-PEO. As the [CL]/[EO] increases, the CMCs of PEO-PCL-PEO decreases and the slope of aggregate size reduction against the copolymer concentration becomes steeper except for the lowest [CL]/[EO] value of PEO-PCL-PEO (i.e., P-222). P-222 significantly increases the viscosity of continuous (W(2)) phase, which implies the copolymer would exist in the W(2) phase. On the other hand, the triblock copolymers with relatively high [CL]/[EO] ratios mainly contribute to the size reduction of multiple emulsions and the formation of a firm wall structure. The particle size of the multiple emulsion decreases and the elastic modulus increased as [CL]/[EO] increases, confirmed by microscopic and rheometric analyses.