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The possibility of controlling periorbital hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. In the current investigation, 1% vitamin K (Vit K) was incorporated into a Chitosan/alginate hydrogel which aimed to increase the dermal delivery and anti-pigmentation effect. The Vit K-hydrogel was evaluated using several different tests, including volume expansion/contraction analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), ultraviolet (UV) absorbance spectroscopy, and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Vit K hydrogel's drug release profile showed a steady increase over time. Furthermore, the modified Vit K hydrogel formulations showed no harmful effects in an in vitro cytotoxicity study. The Vit K hydrogel was tested for dermal irritation on Wistar rats, and the hydrogel was found to be non-irritating. Furthermore, Vit K-hydrogel inhibited melanin formation (31.76 ± 1.14%) and was remarkably higher than free Vit K. In addition, Vit K-hydrogel inhibited L-dopa auto-oxidation to a greater extent (94.80 ± 2.41%) in comparison with Vit K solution (73.95 ± 1.62%). Vit K-hydrogel enhanced percutaneous transport of Vit K, according to in vitro percutaneous absorption findings, suggesting that this innovative formulation may provide new therapeutic options for periorbital hyperpigmentation. [ABSTRACT FROM AUTHOR]

Transdermal administration of chemo therapeutics into burn healing may be an effective treatment to reduce toxic side effects and improve patient compliance for burns. As a transdermal delivery system, Camelina lipid droplets (CLDs) have received great attention due to their biocompatibility, high drug payload, and rapid absorption. However, the absorbed-related mechanisms of Camelina lipid droplets have not yet been reported. Thus, this paper not only demonstrated that CLD can accelerate skin burn healing through promoting hFGF2 absorption, but also elucidated the mechanism between the skin tissue and keratinocytes using Franz, HE staining, DSC, FTIR spectroscopy, and atomic force microscopy with the presence of CLD-hFGF2 freeze-dried powder. We found that the cumulative release rate of CLD-hFGF2 freeze-dried powder was significantly higher than that of free hFGF2 freeze-dried powder into the skin. At the same time, CLD can change the structure and content of lipids and keratin to increase the permeability of hFGF2 freeze-dried powder in skin tissue. Unlike the free state of hFGF2, the biophysical properties of single cells, including height and adhesion force, were changed under CLD-hFGF2 freeze-dried powder treatment. Meanwhile, CLD-hFGF2 freeze-dried powder was more easily taken up through keratinocytes without damaging cell integrity, which provided a new viewpoint for understanding the absorption mechanism with the CLD system for cellular physiology characteristics. Overall, our findings demonstrated that CLD could break through the stratum corneum (SC) barrier and elucidated the transport mechanism of lipid droplets in skin tissue, which provides a crucial guideline in drug delivery applications for future engineering. [ABSTRACT FROM AUTHOR]

Nanomaterials manufactured of amphiphilically‐altered polysaccharides have sparked a great deal of interest due to their capability to elevate drug transport across the skin. The study presents the fabrication of alkylated chitosan through 2‐tert‐butoxymethyloxirane alteration (alkylation degree 29.7%), that was typified by spectroscopic, chromatographic, and thermal analysis approaches before being constructed into nanomaterials for the analysis of their capability in governing fusidic acid diffusion percutaneously. The nanomaterials were constructed via the ionic interaction of positively charged chitosan and negatively charged cross linker sodium tripolyphosphate, with a loading degree of fusidic acid of ca. 20% reported. Fusidic acid release was slower in nanomaterials constructed of alkylated chitosan than in neat chitosan. Under application‐relevant conditions, in vitro incubation with HaCaT cells exhibited insignificant toxicity. Using Franz diffusion cells, the alkylated chitosan nanomaterials induced fusidic acid to infiltrate the Strat‐M® membrane at a 2‐fold greater rate than the neat chitosan nanomaterials. Based on the agar diffusion test, fusidic acid was shown to have better antimicrobial activity when loaded into alkylated chitosan nanomaterials than when loaded into neat chitosan nanomaterials. Ultimately, the in vitro results revealed that alkylated chitosan nanomaterials offer a great deal of potential for percutaneous delivery, which merits greater analysis. [ABSTRACT FROM AUTHOR]

The local treatment of kojic acid (KA) as a tyrosinase inhibitor results in inadequate skin absorption and a number of side effects. The current study aims to maximize KA skin delivery. To produce KA-hydrogel, 1% KA was injected into a Chitosan/alginate hydrogel. The impacts of biopolymer proportion on the KA-hydrogel preparations were investigated. Swelling analysis, weight loss analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), UV absorption spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to evaluate the KA-hydrogel. The swelling percentages of KA-hydrogel increased significantly after 4 h. After two weeks, up to 60% of the primary mass of the KA- hydrogel has been removed. By alternation in biopolymer proportion, the drug release profile of KA-hydrogel demonstrated a sustained pattern. According to the skin absorption experiment, KA-hydrogel had higher skin deposition (25.630 ± 3.350%) than KA-plain gel (5.170 ± 0.340%). Moreover, an in vitro cytotoxicity analysis for the modified KA-hydrogel preparations revealed no cytotoxic effects on HFF cell line (90%). Moreover, KA hydrogel had inhibitory effect on melanin synthesis and are comparable with KA. Furthermore, KA-hydrogel had higher inhibitory effect on L-dopa auto oxidation (94.84 ± 2.41%) in comparison KA solution (73.95 ± 3.28%). Also, the dermal irritation study on Wistar rat revealed that the hydrogel constituent used did not irritate the skin. These results revealed that the KA-hydrogel might be employed as KA local administration, thus opening up new prospects for the therapies of hyperpigmentation problems. [ABSTRACT FROM AUTHOR]

Background: There has been an increase in demand for cosmetic skin-whitening products with efficacy toward lightening skin tone. β-arbutin is an inhibitor of tyrosinase enzyme activity within the skin's melanocytes, and so has shown considerable promise as a skin-lightening agent. It is, however, both hydrophilic and hygroscopic, which hinders its penetration of the skin to reach these melanocytes. Chitosan (CS) possesses considerable penetration-enhancing properties when utilized in topical delivery formulations. The strong affinity of positively charged chitosan nanoparticles toward negatively charged biological membranes can be exploited to achieve site-specific targeting. Objective: To investigate the use of chitosan nanoparticles (CSNPs) as carrier units to enhance the topical delivery of β-arbutin. Method: CSNPs containing β-arbutin were prepared using an ionic cross-linking method, and entrapment efficiency and loading capacity were evaluated at numerous β-arbutin concentrations. Further characterization involved using FTIR, XRD, TEM, and TGA, and in vitro permeation studies were conducted using in vitro Franz diffusion cells. Results: β-arbutin chitosan nanoparticles were successfully formulated with a size range of 211–289 d.nm, a polydispersity index between 0.2–0.3, and zeta potential in the range 46.9–64.0 mV. The optimum encapsulation efficiency (EE) and loading capacity (LC) of β-arbutin were 68% and 73%, respectively. TEM revealed the nanoparticles to be spherical in shape. FTIR spectra revealed characteristic chitosan-related peaks appearing at 3438.3 cm−1 (-OH stretching) and 3320 cm−1 (-CH stretching), together with 1598.01 cm−1 (-NH2) specific to β-arbutin nanoparticles. XRD analysis revealed an increase in crystallinity and TGA analyses identified increasing thermal stability with increasing β-arbutin concentration. In vitro studies indicated higher permeation and improved penetration of β-arbutin loaded in CSNPs compared to its free form. Conclusion: CSNPs present considerable promise as effective carriers for improved topical delivery of β-arbutin. [ABSTRACT FROM AUTHOR]

The study aims to formulate and characterize nanoformulations produced from amphipathically‐modified pectin containing fusidic acid, making clear the importance of nanocarrier amphipathicity in boosting drug permeation through the skin. For this purpose, the amphipathically‐modified pectin (GBE‐PEC) fabrication was achieved following glycidol butyl ether modification via the nucleophilic substitution SN2 reaction, which was then characterized using thermal analysis, spectroscopic, and chromatographic tools. The materials were subsequently converted into spherical nanostructures (NSs) (size 250–290 nm; zeta potential −25 to −34 mV) via a nanoprecipitation in situ cross‐linking approach, demonstrating low viscosity and good colloidal stability under pH 4 conditions. The encapsulated fusidic acid (loading degree 14.9%) was released from GBE‐PEC NSs in a more controlled fashion, with release profiles best characterized by the Higuchi model. Interactions with HaCaT cells in vitro demonstrated no apparent cytotoxicity at application relevant conditions, with efficient cellular absorption as evidenced by flow cytometry analysis. Using Franz diffusion cells, GBE‐PEC NSs had a 2‐fold greater penetration rate through the Strat‐M® membrane than the native pectin NSs. Overall, the study has introduced new insights into the design, fabrication, characterization, and tremendous potential of NSs formulated from GBE‐PEC for percutaneous delivery of poorly penetrating actives, which merit further analysis. [ABSTRACT FROM AUTHOR]

The study focused on formulation of carmellose sodium hydrogels and nonionic microemulsions with 5% and 10% of levetiracetam and investigation of drug concentration influence on their physicochemical characteristics and in-use stability as well as influence of drug concentration and carrier type on in vitro drug release and in vivo antihyperalgesic/antiedematous activity in a rat model of localized (intraplantar) carrageenan-induced inflammation. Hydrogels were pseudoplastic semisolids with thixotropy and pH 7.37–7.58. Microemulsions were low viscous Newtonian nanodispersions of oil droplets (13.11–15.11 nm) in water, with pH 4.01–4.64. Physical stability of the investigated systems was preserved over the 3-month storage under ambient conditions. Levetiracetam release followed zero order and Korsmeyer-Peppas models (R2 ≥ 0.99) reflecting the combined effects of drug concentration and carrier viscosity. All levetiracetam-loaded formulations produced significant reduction of hyperalgesia and paw swelling induced by carrageenan (p < 0.001). Their efficacy in exerting antihyperalgesic activity was significantly higher than that observed with the reference 5% ibuprofen hydrogel preparation (up to 6 h) (p < 0.001), while antiedematous activity was comparable with the reference product. No erythema and visible blood vessels were observed in a rat ear test. The study demonstrated percutaneous delivery of levetiracetam as useful and safe therapeutic option for localized inflammatory pain with potential to overcome the insufficient efficacy of topically applied nonsteroidal anti-inflammatory drugs in the form of a hydrogel. [ABSTRACT FROM AUTHOR]

Tamoxifen (TAM) is frequently prescribed for the management breast cancer, but is associated with the challenges like compromised aqueous solubility and poor bioavailability to the target site. It was envisioned to develop phospholipid-based mixed micelles to explore the promises offered by the biocompatible carriers. Various compositions were prepared, employing soya lecithin, polysorbate 80, sodium chloride/dextrose, and water, by self-assembled technique. The formulations were characterized for micromeritics and evaluated for in vitro drug release, hemolysis study, dermatokinetic studies on rodents, and cytotoxicity on MCF-7 cell lines. Cellular uptake of the system was also studied using confocal laser scanning microscopy. The selected composition was of sub-micron range (28.81 ± 2.1 nm), with spherical morphology. During in- vitro studies, the mixed micelles offered controlled drug release than that of conventional gel. Cytotoxicity was significantly enhanced and IC value was reduced that of the naïve drug. The bioavailability in epidermis and dermis skin layers was enhanced approx. fivefold and threefold, respectively. The developed nanosystem not only enhanced the efficacy of the drug but also maintained the integrity of skin, as revealed by histological studies. The developed TAM-nanocarrier possesses potential promises for safe and better delivery of TAM. [ABSTRACT FROM AUTHOR]

Prosthetic annuloplasty rings are a common treatment modality for mitral regurgitation, and recently, percutaneous implantation techniques have gained popularity due to their favorable safety profile. Although in common use, biocompatibility of annuloplasty rings has been reported only sparsely in the literature, and none of these reports used the percutaneous technique of implantation. We report on the biocompatibility and the systemic safety of a novel transcatheter mitral valve annuloplasty ring (AMEND™) in 6 minipigs. This device is composed of a nitinol tube surrounded by a braided polyethylene terephthalate fabric tube. The device produced no adverse inflammatory response, showing gradual integration between the metal ring and the fabric by normal host fibrocellular response, leading to complete neoendocardium coverage. There was no evidence for adverse reactions, rejection, or intolerance in the valvular structure. In 2 animals, hemopericardium resulted from the implantation procedure, leading to right-sided cardiac insufficiency with pulmonary edema and liver congestion. The findings reported herein can serve as a case study for the expected healing pathology reactions after implantation of transcatheter mitral valve annuloplasty rings. [ABSTRACT FROM AUTHOR]

A study that combines microneedles (MNs) and sonophoresis pre-treatment was explored to determine their combined effects on percutaneous delivery of lidocaine from a polymeric hydrogel formulation. Varying ratios of carboxymethylcellulose and gelatine (NaCMC/gel ranges 1:1.60–1:2.66) loaded with lidocaine were prepared and characterized for zeta potential and particle size. Additionally, variations in the formulation drying techniques were explored during the formulation stage.Ex vivopermeation studies using Franz diffusion cells measured lidocaine permeation through porcine skin after pre-treatment with stainless steel MNs and 20 kHz sonophoresis for 5-and 10-min durations. A stable formulation was related to a lower gelatine mass ratio because of smaller mean particle sizes and high zeta potential. Lidocaine permeability in skin revealed some increases in permeability from combined MN and ultrasound pre-treatment studies. Furthermore, up to 4.8-fold increase in the combined application was observed compared with separate pre-treatments after 30 min. Sonophoresis pre-treatment alone showed insignificant enhancement in lidocaine permeation during the initial 2 h period. MN application increased permeability at a time of 0.5 h for up to ∼17 fold with an average up to 4 fold. The time required to reach therapeutic levels of lidocaine was decreased to less than 7 min. Overall, the attempted approach promises to be a viable alternative to conventional lidocaine delivery methods involving painful injections by hypodermic needles. The mass transfer effects were fairly enhanced and the lowest amount of lidocaine in skin was 99.7% of the delivered amount at a time of 3 h for lidocaine NaCMC/GEL 1:2.66 after low-frequency sonophoresis and MN treatment. [ABSTRACT FROM AUTHOR]

Common local anaesthetics such as lidocaine are administered by the hypodermic parenteral route but it causes pain or anxiety to patients. Alternatively, an ointment formulation may be applied which involves a slow drug diffusion process. In addressing these two issues, this paper aims to understand the significance of the 'poke and patch' microneedle (MN) treatment on skin in conjunction to the lidocaine permeation, and in particular, the vertical (depth averaged) and horizontal (e.g. lateral) permeation profiles of the drug in the skin. The instantaneous pharmacokinetics of lidocaine in skin was determined by a skin denaturation technique coupled with Franz diffusion cell measurements of the drug pharmacokinetics. All pharmacokinetic profiles were performed periodically on porcine skin. Three MN insertion forces of 3.9, 7.9 and 15.7 N were applied on the MN to pierce the skin. For the smaller force (3.9 N), post MN-treated skin seems to provide an 'optimum' percutaneous delivery rate. A 10.2-fold increase in lidocaine permeation was observed for a MN insertion force of 3.9 N at 0.25 h and similarly, a 5.4-fold increase in permeation occurred at 0.5 h compared to passive diffusional delivery. It is shown that lidocaine permeates horizontally beyond the area of the MN-treated skin for the smaller MN insertion forces, namely, 3.9 and 7.9 N from 0.25 to 0.75 h, respectively. The lateral diffusion/permeation of lidocaine for larger MN-treated force (namely, 15.7 N in this work) seems to be insignificant at all recorded timings. The MN insertion force of 15.7 N resulted in lidocaine concentrations slightly greater than control (passive diffusion) but significantly less than 3.9 and 7.9 N impact force treatments on skin. We believe this likelihood is due to the skin compression effect that inhibits diffusion until the skin had time to relax at which point lidocaine levels increase. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to develop an optimal microemulsion (ME) formulation as topical nanocarrier of caffeine (CAF) to enhance CAF skin retention and subsequently improve its therapeutic effect on UVB-induced skin carcinogenesis. The pseudo-ternary phase diagram was developed composing of Labrafil M 1944 CS as oil phase, Cremophor EL as surfactant, tetraglycol as cosurfactant, and water. Four ME formulations at water content of 50, 60, 70, and 80% were prepared along the water dilution line of oil to surfactant ratio of 1:3 and characterized in terms of morphology, droplet size, and electric conductivity. A gel at the same drug loads (1%, w/ w) was used as control. Ex vivo skin permeation studies were conducted for ME optimization. The optimized formulation (ME4) was composed of 5% ( w/ w) Labrafil M 1944 CS, 15% ( w/ w) Smix (2/1, Cremophor EL and tetraglycol), and 80% ( w/ w) aqueous phase. The skin location amount of CAF from ME4 was nearly 3-fold higher than control ( P < 0.05) with improved permeated amount through the skin. The skin targeting localization of hydrophilic substance from ME4 was further visualized through fluorescent-labeled ME by a confocal laser scanning microscope. In pharmacodynamics studies, CAF-loaded ME4 was superior in terms of increasing apoptotic sunburn cells ( P < 0.05) as compared with control. Overall results suggested that the ME4 might be a promising vehicle for the topical delivery of CAF. [ABSTRACT FROM AUTHOR]

Percutaneous heart valves provide a promising future for patients refused surgery on the grounds of significant technical challenges or high risk for complications. Since the first human intervention more than 10 years ago, over 50 different types of valves have been developed. The CoreValve and Edwards SAPIEN valves have both experienced clinical trials and the latter has gained FDA approval for implantation in patients considered inoperable. Current complications, such as major vascular bleeding and stroke, prevent these valves from being commonly deployed in patients considered operable in conventional surgery. This review focuses on the past and present achievements of these valves and highlights the design considerations required to progress development further. It is envisaged that, with continued improvement in valve design and with increased clinical and engineering experience, percutaneous heart valve replacement may one day be a viable option for lower-risk operable patients. [ABSTRACT FROM PUBLISHER]

We encapsulated recombinant human epidermal growth factor (rhEGF) into nano-liposomes (NLs) system for topical delivery. The rhEGF-loaded NLs were prepared using a high pressure homogenization method. Morphology and overall particle distribution of NLs were investigated using transmission electron microscopy (TEM) and high resolution microscope (CytoViva™). Particle size, zeta ( ζ) potential and encapsulation efficiency were measured and the percutaneous delivery of NLs was evaluated using Franz diffusion cells and immunofluorescence confocal laser scanning microscopy (CLSM). The mean particle size, zeta potential and encapsulation efficiency of the NLs were 155.57 ± 2.59 nm, −57.92 ± 4.35 mV and 9.00 ± 0.39%%, respectively. TEM and microscopic analysis showed spherical, very even-sized vesicles approximately 150 nm. The skin permeation and localization of rhEGF were enhanced by NLs. CLSM image analysis provided that the NLs enhanced the permeation and localization of rhEGF in rat skin by facilitating entry through pores of skin. [ABSTRACT FROM AUTHOR]

At present, no widely accepted surgical options exist for treating chronic deep venous insufficiency (CDVI). Experimental efforts to improve catheter-based management for CDVI have shown disappointing results, hindering application of these techniques in the clinical arena. A review of the literature focusing on technical aspects of valve stent design was conducted. Eight experimental studies were scrutinized to derive data on (1) stent design and configuration; (2) valve design, composition, and configuration; (3) delivery system; (4) functional outcome; and (5) histology to provide a basis for the design of a new prosthetic venous valve. The analysis of available experimental data found that all prosthetic valve designs currently under development/testing rely on some type of a stent to act as a carrier or frame for valve attachment. Most valve models reviewed were for the most part implanted safely and accurately, with good short-term patency and competency. The most commonly reported adverse event was thrombosis, which limited durability. It is assumed that valve configuration determines long-term results after repair. Hence, the newly proposed valve design consisted of 2 stent rings without barbs to fix the valve in the host vein. Because a little reflux might actually benefit the patency of the valve, the valve cusp in the new design forms a billowing 'sail' that does not completely open or close, which also prevents the valve cusp from sticking to the wall. This technology remains of great interest to the interventionist and all physicians who are involved in the care for patients with advanced chronic venous disease. Valve design remains a challenge, but promising new valve substitutes such as the one outlined here are under evaluation. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study was to determine the permeation parameters of thalidomide and three of its N-alkyl analogs and to establish a correlation between the physicochemical properties of these compounds and their percutaneous rates of absorption. Methods. In vitro permeation studies were performed from buffer, n-alkanols and various mixed components using vertical Franz diffusion cells fitted with human epidermal membranes. Results. Measured steady-state fluxes indicate that N-methyl thalidomide is a far better penetrant of human skin than the “parent molecule”. However, fluxes through skin drop off markedly from that of the methylated compound when the chain length is extended to propyl and pentyl. However, they remain well above the flux of thalidomide, which is less than 0.025 μg/cm2/h. Conclusions. The best skin permeant of this series was the N-methyl analog, which also exhibited the highest water (buffer) solubility compared to thalidomide, and the N-propyl and N-pentyl analogs. The N-propyl and N-pentyl analogs were more lipid soluble and exhibited higher partition coefficient values than the N-methyl analog. From all the permeability data using buffer, a series of n-alkanols and various combinations of solvents and enhancers as vehicles, the more water-soluble compound and not the more lipid soluble one was the best skin permeant. [ABSTRACT FROM AUTHOR]

Arthritis is a heterogeneous group of conditions that leads to joint symptoms and signs which are associated with defective integrity of articular cartilage. Major classes of drugs which are widely used for the treatment of arthritis are Non-Steroidal Anti-inflammatory Drugs (NSAIDs). Development of an efficient means of percutaneous delivery can increase drug concentration in local soft-tissues and joints while reducing the systemic distribution of a drug and its side effects. The present work is aimed at synthesisand evaluation of prodrugs of some NSAIDs for percutaneous drug delivery for the treatment of arthritis. [ABSTRACT FROM AUTHOR]