Nanoscaled pearl powder accelerates wound repair and regeneration in vitro and in vivo.

Pearl powder has been used to treat many diseases like palpitations, insomnia, and epilepsy for thousands of years in Chinese medicine. It has demonstrated antioxidant, antiaging, antiradiative, and tonic activities. Pearl powder contains multiple active proteins, which are nutritious for skin cells and might be advantageous for wound repair and regeneration. However, its healing effect in vivo was not reported yet. This study aims to investigate the effects and the underlying mechanism of the pearl powders with different particle sizes in wound treatment. Briefly, the pearl powder with different sizes was characterized for their particle sizes and morphology. The protein release profiles of these powders were also studied. The influence of the different size of pearl powder in the proliferation, migration of skin cells was evaluated. Then, with the rat skin excision model, the effect of pearl powder on wound repair and regeneration was investigated. It was demonstrated that, all the micro and nanosized pearl powders could both increase the proliferation and migration of skin cells and accelerate the wound closure, as well as significantly enhanced the biomechanic strength of the healed skins. Moreover, the pearl powder treatment could improve the formation and regular deposition of collagen, and enhance the skin angiogenesis. Among all these in vitro and in vivo investigations, nanoscale pearl powder expressed the highest efficiency for healing. The mechanism might be contributed to the increased release of active proteins, enhanced tissue attachment, and the increased cellular uptake for the nano powder at the topical site.

Sequential release of salidroside and paeonol from a nanosphere-hydrogel system inhibits ultraviolet B-induced melanogenesis in guinea pig skin.

Melanin is the one of most important pigments for skin color in mammals. Excessive biosynthesis of melanin induces various pigment disorders. Much effort has been made to develop regulators to minimize skin pigmentation abnormalities. However, only a few of them are used, primarily because of safety concerns and low efficiency. In this study, we aimed to construct a novel nanosphere-gel for sequential delivery of salidroside and paeonol, to investigate the synergistic effects of these drugs in anti-melanogenesis, and to decrease their potential for toxicity in high dosage. Nanospheres were prepared and characterized for their particle size, polydispersity index, zeta potential, and morphological properties. The optimized nanospheres were incorporated in carbomer hydrogel with both paeonol and salidroside entrapped to form a dual drug-releasing nanosphere-gel. With this nanosphere-gel, rapid release of salidroside from the hydrogel followed by sustained release of paeonol from the nanosphere was achieved. Using a classical model of the melanogenesis response to ultraviolet exposure, it was shown that the anti-melanogenesis effects of the dual drug-releasing system, in which the doses of the individual drugs were decreased by half, was obviously enhanced when compared with the effects of the single drug preparations. Mechanistically, the burst release of salidroside from the hydrogel may enable prompt suppression of melanocyte proliferation on exposure to ultraviolet B radiation, while the paeonol released in a sustained manner can provide continuous inhibition of tyrosinase activity in melanocytes. Combined delivery of salidroside and paeonol was demonstrated to be a promising strategy for enhancing the therapeutic efficacy of these agents in anti-melanogenesis and reducing their toxicity, so may have great potential in nanomedicine.

Inhibitory effects of salidroside and paeonol on tyrosinase activity and melanin synthesis in mouse B16F10 melanoma cells and ultraviolet B-induced pigmentation in guinea pig skin.

Salidroside, the major active component of Rhodiola rosea, a herb with antioxidant, free radical scavenging and tyrosinase inhibitory effects, has been recently reported in protecting the kerationcytes from the UV radiation, suggesting the potential of this component in depigmentation. Paeonol is isolated from Moutan Cortex Radicis with anti-inflammation/microbial activities, was reported to induce the down-regulation of microphthalmia-associated transcription factor and subsequently tyrosinase. To testify the potential of these compounds as melanin formation inhibitors for hyperpigmentation therapy, the influence of salidroside and paeonol on pigmentation was investigated. With arbutin as a positive control, salidroside and paeonol were evaluated for their inhibitory effect on the cell viability, tyrosinase activity and melanin synthesis in B16F10 melanoma cells, as well as their effects in UVB-induced hyperpigmentation in brown guinea pig skins. It was demonstrated that the significant inhibition of salidroside (33.0%) and paeonol (22.2-30.9%) on the tyrosinase activity is slightly lower than that of arbutin (18.4-44.7%). However, salidroside exhibited the dose-dependent inhibition (30.6-42.0%) in melanin synthesis at a low concentration of 100 µM, paeonol and arbutin expressed inhibition rates of 27.4-37.2% and 25.8-45.6% within 500-1000 µM. The in vivo topical application of these compounds was demonstrated to obviously decrease the hyperpigmentation on UVB stimulated guinea pig skin. This study provided the original evidence for the salidroside and paeonol as therapeutic agents for pigmentation disorder and skin lightening, with further clinical investigation of these compounds in the field of depigmentation was suggested.

Astragaloside IV-loaded nanoparticle-enriched hydrogel induces wound healing and anti-scar activity through topical delivery.

This study aims to investigate the novel preparation of solid lipid nanoparticle-enriched hydrogel (SLN-gel) for the topical delivery of astragaloside IV and to determine the effects of astragaloside IV-based SLN-gel on wound healing and anti-scar formation. Solid lipid nanoparticles (SLNs) were prepared through the solvent evaporation method. The particle size, polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), drug release, and morphological properties of the SLNs were characterized. The optimized SLNs were incorporated in carbomer hydrogel to form an SLN-enriched gel (SLN-gel) carrier. The effects of astragaloside IV-enriched SLNs on wound healing were determined using the wound scratch test, and their uptake by skin cells was tested in vitro. With the rat full-skin excision model, the in vivo regulation of astragaloside IV-based SLN-gel in the wound stages of re-epithelization, angiogenesis, and extracellular matrix remodeling was investigated. The best formulation of astragaloside IV-based SLNs had high EE (93% ± 5%) and ZP (-23.6 mV ± 1.5 mV), with a PDI of 0.18 ± 0.03 and a drug loading percentage of 9%. Astragaloside IV-based SLNs and SLN-gel could release drug sustainably. Astragaloside IV-based SLNs enhanced the migration and proliferation of keratinocytes and increased drug uptake on fibroblasts in vitro (P<0.01) through the caveolae endocytosis pathway, which was inhibited by methyl-ß-cyclodextrin. Astragaloside IV-based SLN-gel strengthened wound healing and inhibited scar formation in vivo by increasing wound closure rate (P<0.05) and by contributing to angiogenesis and collagen regular organization. SLN-enriched gel is a promising topical drug delivery system. Astragaloside IV-loaded SLN-enriched gel was proven as an excellent topical preparation with wound healing and anti-scar effects.

The healing and anti-scar effects of astragaloside IV on the wound repair in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragaloside IV is the chief ingredient of Radix Astragali, which has been used in the Traditional Chinese Medicine as a major component of many polyherbal formulations for the repair and regeneration of injured organ and tissues. This study is to investigate the influence of astragaloside IV on both of the wound healing and scar formation. MATERIALS AND METHODS: For the in vitro evaluation, the influence of the astragaloside IV in the wound scratch test of keratinocytes and the secretion of transforming growth factor-ß1, a key factor contributing to scar formation were determined. With the rat skin excision model, the in vivo regulation of astragaloside IV on wound closure, angiogenesis and collagen disposition were also evaluated. RESULTS: Astragaloside IV was shown to significantly promote the migration of keratinocytes in wound scratching assay. The superior effect of Astragaloside IV was observed at 100 µmol/L, in which the recover rates was increased with 2 and 3 folds after 48 h and 96 h respectively than that of blank control (P<0.01). Animal skin closure measurement showed that astragaloside IV could stimulate the wound healing, e.g. with 21% recover in contrast to the 8% of blank control at the 6th day. Biomechanic and Masson's trichrome stain analysis indicated that astragaloside IV may improve the strength of the repaired skin and promoted the angiogenesis and collagen synthesis. Meanwhile, the picrosirius-sirus red stain and Elisa test definitely showed the anti-scar effects of astragaloside IV by decreasing the levels of collagen I/III and TGF-ß1 secretion by firbroblasts with a dose-dependent manner (25-100 µmol/L). CONCLUSIONS: Astragaloside IV was shown a promising natural product with both healing and anti-scar effects for wound treatment. These results give the evidence for the application of astragaloside IV in the treatment of injury.

In vitro and in vivo evaluation of a novel capsule for colon-specific drug delivery.

The aim of this study was to estimate colon-specific drug delivery of a novel capsule (CS capsule). Theophylline was used as model drug and little was released from the CS capsules in the release medium mimicking physiological environment of stomach to small intestine. However, 66.7 +/- 8.8% theophylline was released from the capsules in the phosphate buffer (pH 6.8) mimicking the physiological environment of colon in the next 4 h, while the addition of galactomannanase (39.3 U/L) accelerated the disintegration of the CS capsule and enhanced the release rate to 92.6 +/- 6.0%. Rats in vivo pharmacokinetics demonstrated that the relative bioavailability of theophylline after intragastric administration of CS capsules was 76.72% with delayed T(max) of 8 h comparing to that of theophylline solution with T(max) of 1.5 h. Radiolabeled with technetium-99m, the CS capsule could keep intact from stomach to small intestine while disintegration of the CS capsule was observed in the proximal colon or the joint between the distal small intestine and right colon. A great quantity of radiolabeled marker was released as well as distributed in the whole colon at 10 h after administration. As a whole, the CS capsule prepared could provide an alternative carrier for the colon-specific drug delivery.

[Influence of different penetration enhancers on Lappaconitine transcutaneous permeation].

OBJECTIVE: To investigate the effects of different kinds and concentration of transdermal enhancers on Lappaconitine transcutaneous permeation when used individually or together. METHOD: Using modified Franz-type diffusion cell and excised human body skin as an in vitro transdermal model, the concentration of lappaconitine was determined by HPLC, then cumulative permeation quantity (Q) and stability rate (J) of progesterone were calculated. RESULT: Penetration enhancers such as propylene glycol, dodecanol, IPM, and particularly 3% OA and Azone, can significantly enhance the penetration rate of lappaconitine. Concentration effect of penetration enhancers concentration on lappaconitine transcutaneous permeation were found in experiments, the permeation effect of Azone was better than Azone + OA and Azone + propylene glycol. CONCLUSION: The transdermal rate of lappaconitine from batch which contains 3% OA or Azone is higher than others. Combination of Azone with other penetration enhancers is not recommended for Lappaconitine transcutaneous permeation.

[Study on alpha-asarone reservoir-type patch].

OBJECTIVE: To prepare the alpha-asarone reservoir patch and investigate its release and transdermal absorption characteristics in vitro. The efficient enhancers were chosen to improve the drug's permeation rate. METHOD: The alpha-asarone reservoir patch was prepared using 1% hydroxypropyl methylcellulose (HPMC) of ethanol solution as medium and ethylene vinyl acetate (EVA) membrane to control the release of drug. The Franz diffusion cells were used and several permeation enhancers were evaluated. High performance liquid chromatorgraphy (HPLC) was used to determine alpha-asarone's content and permeation rate. RESULT: The release mechanisms of alpha K-asarone patch in vitro coincided with zero-order kinetic. 30% ethanol cooperates with 1% Isopropyl Myristate (IPM) have the best effect on permeation of the patch. The permeation rate reaches (20.67 +/- 1.33) microg x cm(-2) h(-1). CONCLUSION: Ethanol combined with IPM is good permeation enhancer, which facilitated the permeation of alpha K-asarone to fit the clinical requirements. However, the further studies of the skin's stimulation and bioavailability are needed.