Abstract Growth factor therapies to induce angiogenesis and thereby enhance the blood perfusion, hold tremendous potential to address the shortcomings of current impaired wound care modalities. ...Vascular endothelial growth factor stimulates (VEGF) wound healing via multiple mechanisms. Poly(lactic- co -glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. Hence, we hypothesized that the administration of VEGF encapsulated in PLGA nanoparticles (PLGA-VEGF NP) would promote fast healing due to the sustained and combined effects of VEGF and lactate. In a splinted mouse full thickness excision model, compared with untreated, VEGF and PLGA NP, PLGA-VEGF NP treated wounds showed significant granulation tissue formation with higher collagen content, re-epithelialization and angiogenesis. The cellular and molecular studies revealed that PLGA-VEGF NP enhanced the proliferation and migration of keratinocytes and upregulated the expression of VEGFR2 at mRNA level. We demonstrated the combined effects of lactate and VEGF for active healing of non-diabetic and diabetic wounds. From the Clinical Editor The study of wound healing has been under a tremendous amount of research over recent years. In diabetic wounds, vasculopathy leading to localized ischemia would often result in delayed wound healing. In this article, the authors encapsulated vascular endothelial growth factor stimulates (VEGF) in PLGA nanoparticles and studies the potential pro-healing effects. It was found that the combination of these two components provided synergistic actions for healing. The encouraging results should provide a basis for combination therapy in the future.
The use of colloidal silica nanoparticles and sub‐microparticles (SiPs) have been considered a very interesting strategy for drug delivery applications. In the present study, we have focused our ...attention on the suitability of these nanomaterials as potential carriers for dermal drug delivery, thus studying their toxicological profile in vitro, cellular uptake and intracellular localization in both human keratinocytes (K17) and human dermal fibroblasts (HDF) as a function of their particle size (SiPs of 20, 70, 200 and 500 nm). Full characterization of these aspects enabled us to observe a strong cell‐type dependency in terms of cytotoxicity and cell internalization, whereas particle size was only relevant for ultra‐small SiPs (20 nm), being the most toxic SiPs. For 70, 200 and 500 nm SiPs, the differences in uptake and intracellular trafficking determined the different toxicological profiles in K17 and HDF. In addition, these characteristics can further define different drug delivery strategies. Hence, phagocytosis has been identified as the main internalization mechanism for K17, and caveolae‐mediated endocytosis for HDF. This relevant information led us to conclude that fibroblasts would be optimal targets for delivering delicate therapeutic molecules such as proteins or genetic material using SiPs while maintaining a low toxicity profile, whereas keratinocytes could enable accelerated drug release therapies based on SiPs.
The toxicological characterization of silica particles (SiPs) in keratinocytes and fibroblasts evidenced a strong cell type dependency in terms of cytotoxicity and internalization. Particle size was only relevant for ultra‐small SiPs (20 nm), being the most toxic SiPs. Phagocytosis and caveolae‐mediated endocytosis were identified as main entry pathways for keratinocytes and fibroblasts, respectively. These differences determine their different toxic effect in both cell types and enable to define adequate drug delivery strategies.
Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates ...neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles.
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Dacarbazine (Dac) is one of the most commonly used chemotherapy drugs for treating various cancers. However, its poor water solubility, short half-life in blood circulation, low response rate and ...high side effect limit its application. This study aimed to improve the drug solubility and prolong drug release by developing nanostructured lipid carriers (NLCs) for Dac delivery. The NLC and Dac-encapsulated NLC were synthesized with precirol ATO 5 and isopropyl myristate as lipids, tocopheryl polyethylene glycol succinate, soybean lecithin and Kolliphor P 188 as co-surfactants. The NLCs with controlled size were achieved using high shear dispersion following solidification of oil-in-water emulsion. For Dac encapsulation, the smallest NLC with 155 ± 10 nm in size, 0.2 ± 0.01 polydispersion index and −43.4 ± 2 mV zeta potential was selected. The resultant DLC-Dac possessed size, polydispersion index and zeta potential of 190 ± 10, 0.2 ± 0.01, and −43.5 ± 1.2, respectively. The drug encapsulation efficiency and drug loading were 98.5 % and 14 %, respectively. In vitro drug release study showed a biphasic pattern, with 50 % released in the first 2 h, and the remaining released sustainably for up to 30 h. This is the first report on the development of NLC for Dac delivery, implying that NLC could be a new potential candidate as drug carrier to improve the therapeutic profile of Dac.
Human growth is a complex trait determined by genetic factors in combination with external stimuli, including environment, nutrition and hormonal status. In the past, several genome-wide association ...studies (GWAS) have collectively identified hundreds of genetic variants having a putative effect on determining adult height in different worldwide populations. Theoretically, a valuable approach to better understand the mechanisms of complex traits as adult height is to study a population exhibiting extreme stature phenotypes, such as African Baka Pygmies. After phenotypic characterization, we sequenced the whole exomes of a cohort of Baka Pygmies and their non-Pygmies Bantu neighbors to highlight genetic variants associated with the reduced stature. Whole exome data analysis revealed 29 single nucleotide polymorphisms (SNPs) significantly associated with the reduced height in the Baka group. Among these variants, we focused on SNP rs7629425, located in the 5′-UTR of the Hyaluronidase-2 (
HYAL2
) gene. The frequency of the alternative allele was significantly increased compared to African and non-African populations. In vitro luciferase assay showed significant differences in transcription modulation by rs7629425 C/T alleles. In conclusion, our results suggested that the
HYAL2
gene variants may play a role in the etiology of short stature in Baka Pygmies population.
Background: Silica is the common name for silicon dioxide (SiO2) materials and exists in both crystalline and amorphous forms. While crystalline silica is known for its severe health effects, ...amorphous silica has been considered safe and applied in many areas. However, some recent studies have showed evidence of their toxicity, raising concerns about its use as nanomaterial for biomedical applications. When nanomaterials enter the body, they are enveloped in biological fluids rich in biomolecules, which compete for binding to the nanomaterial. Such effect could alter their surface chemistry and therefore affect their bio-distribution and interaction with cells. Aim and objectives: As part of the EU-funded NANODRUG network programme, the aim of this project was the in vitro toxicity assessment of commercially-sourced fumed and colloidal amorphous silica particles in relation to their physico-chemical properties and potential application as carriers for drug delivery. The objectives were 1) characterization of silica particles hydrodynamic (Hd) size and dispersity in different cell culture media; 2) in vitro toxicological assessment of silica particles in human skin cells; 3) delineation of toxicity mechanisms in relation to their size; 4) assessment of the influence of Foetal Bovine Serum (FBS) on particle Hd size and toxicity; and 5) contributing to the overall objective of the NANODRUG programme - development of safe nanodrugs for skin application - through collaborations with different partners.
Background: Silica is the common name for silicon dioxide (SiO2) materials and exists in both crystalline and amorphous forms. While crystalline silica is known for its severe health effects, ...amorphous silica has been considered safe and applied in many areas. However, some recent studies have showed evidence of their toxicity, raising concerns about its use as nanomaterial for biomedical applications. When nanomaterials enter the body, they are enveloped in biological fluids rich in biomolecules, which compete for binding to the nanomaterial. Such effect could alter their surface chemistry and therefore affect their bio-distribution and interaction with cells. Aim and objectives: As part of the EU-funded NANODRUG network programme, the aim of this project was the in vitro toxicity assessment of commercially-sourced fumed and colloidal amorphous silica particles in relation to their physico-chemical properties and potential application as carriers for drug delivery. The objectives were 1) characterization of silica particles hydrodynamic (Hd) size and dispersity in different cell culture media; 2) in vitro toxicological assessment of silica particles in human skin cells; 3) delineation of toxicity mechanisms in relation to their size; 4) assessment of the influence of Foetal Bovine Serum (FBS) on particle Hd size and toxicity; and 5) contributing to the overall objective of the NANODRUG programme - development of safe nanodrugs for skin application - through collaborations with different partners.
The development of tools to quickly identify the fate of damaged trees after a stress event such as a wildfire is of great importance. In this context, an innovative approach to assess irreversible ...physiological damage in trees could help to support the planning of management decisions for disturbed sites to restore biodiversity, protect the environment and understand the adaptations of ecosystem functionality. The vitality of trees can be estimated by several physiological indicators, such as cambium activity and the amount of starch and soluble sugars, while the accumulation of ethanol in the cambial cells and phloem is considered an alarm sign of cell death. However, their determination requires time-consuming laboratory protocols, making the approach impractical in the field. Biosensors hold considerable promise for substantially advancing this field. The general objective of this review is to define a system for quantifying the plant vitality in forest areas exposed to fire. This review describes recent electrochemical biosensors that can detect plant molecules, focusing on biosensors for glucose, fructose, and ethanol as indicators of tree vitality.
Metal halide perovskites are the first solution processed semiconductors that can compete in their functionality with conventional semiconductors, such as silicon. Over the past several years, ...perovskite semiconductors have reported breakthroughs in various optoelectronic devices, such as solar cells, photodetectors, light emitting and memory devices, and so on. Until now, perovskite semiconductors face challenges regarding their stability, reproducibility, and toxicity. In this Roadmap, we combine the expertise of chemistry, physics, and device engineering from leading experts in the perovskite research community to focus on the fundamental material properties, the fabrication methods, characterization and photophysical properties, perovskite devices, and current challenges in this field. We develop a comprehensive overview of the current state-of-the-art and offer readers an informed perspective of where this field is heading and what challenges we have to overcome to get to successful commercialization.
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