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1.
Pharmaceuticals (Basel) ; 17(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38256910

RESUMO

Inflammatory skin diseases, such as psoriasis, atopic dermatitis, and alopecia areata, occur when the regulatory tolerance of the innate immune system is disrupted, resulting in the activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inflammatory signaling pathway by interleukin 6 (IL-6) and other key inflammatory cytokines. JAK inhibitors, such as tofacitinib, bind to these enzymes which are coupled to receptors on cell surfaces and block the transcription of inflammatory cytokine-induced genes. The first topical applications are being marketed, yet insufficient effects regarding indications, such as alopecia areata, suggest that improved delivery technologies could help increase the efficacy. In this study, we used sulfated dendritic polyglycerol with caprolactone segments integrated in its backbone (dPGS-PCL), with a molecular weight of 54 kDa, as a degradable carrier to load and solubilize the hydrophobic drug tofacitinib (TFB). TFB loaded in dPGS-PCL (dPGS-PCL@TFB), at a 11 w/w% loading capacity in aqueous solution, showed in an ex-vivo human skin model better penetration than free TFB in a 30:70 (v/v) ethanol/water mixture. We also investigated the anti-inflammatory efficacy of dPGS-PCL@TFB (0.5 w/w%), dPGS-PCL, and free TFB in the water/ethanol mixture by measuring their effects on IL-6 and IL-8 release, and STAT3 and STAT5 activation in ex vivo skin models of simulated inflamed human skin. Our results suggest that dPGS-PCL@TFB reduces the activation of STAT3 and STAT5 by increasing the penetration of the tofacitinib. However, no statistically significant differences with respect to the inhibition of IL-6 and IL-8 were observed in this short incubation time.

2.
Soft Matter ; 20(6): 1282-1292, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38240025

RESUMO

C 3-symmetric star-shaped aromatic compounds are known to possess unique characteristics which facilitate their industrial and biomedical applications. Herein, we report the design, synthesis, self-assembly and drug/dye delivery capabilities of C3-symmetric, hexa-substituted benzene-based amphiphiles. The synthesis of the hexa-substituted C3-symmetric core involves C-acetylation of phloroglucinol to yield the corresponding tri-acetyl derivative. This was further subjected to O-propargylation, followed by the carbonyl reduction of acetyl groups to yield the central core. Various hydrophilic (mPEG) and lipophilic units were then incorporated into this core via click and esterification reactions, respectively, to produce a new type of star shaped amphiphiles. So the obtained amphiphilic architectures have a tendency to aggregate in an aqueous medium forming nanosized assemblies with an inner hydrophobic core, allowing the substituents to control the tension-active properties. The critical aggregation concentration of the amphiphiles was evaluated by fluorescence measurement using the dye Nile red as a fluorescent probe. The hydrodynamic diameter of self-assembled aggregates in aqueous solution was studied by dynamic light scattering, while the actual size and morphology were determined by cryo-transmission electron microscopy (cryo-TEM) analysis. The physicochemical properties of the amphiphiles suggested their suitability for exploring their drug delivery applications. In this endeavor, the amphiphiles were utilized for the encapsulation of model hydrophobic entities and studying their subsequent release from their hydrophobic core in a controlled manner. The transport potential of the synthesised amphiphiles was explored for transdermal drug delivery. Furthermore, cytotoxicity studies were conducted using MCF7 and HeLa cells, which indicated that the nanocarriers had no toxic effect on the cells.


Assuntos
Sistemas de Liberação de Medicamentos , Micelas , Humanos , Células HeLa , Corantes Fluorescentes/química
3.
ACS Appl Mater Interfaces ; 15(48): 56213-56222, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37992272

RESUMO

Manipulation of the structure of covalent organic frameworks at the molecular level is an efficient strategy to shift their biological, physicochemical, optical, and electrical properties in the desired windows. In this work, we report on a new method to construct chiral triazine frameworks using metal-driven polymerization for enantiodiscrimination. The nucleophilic substitution reaction between melamine and cyanuric chloride was performed in the presence of PdCl2, ZnCl2, and CuCl2 as chirality-directing agents. Palladium, with the ability of planar complex formation, was able to assemble monomers in two-dimensions and drive the reaction in two directions, leading to a two-dimensional triazine network with several micrometers lateral size. Nonplanar arrangements of monomers in the presence of ZnCl2 and CuCl2, however, resulted in calix and bouquet structures, respectively. While 2D and bouquet structures showed strong negative and positive bands in the CD spectra, respectively, their calix counterparts displayed long-range weak negative bands. In spite of the ability of both calix and bouquet networks to load l-histidine 35 and 50% more than d-histidine from pure enantiomers, respectively, only calix counterparts were able to take up this enantiomer (78%) from the racemic mixture. The two-dimensional polytriazine network did not show any specific interactions with pure enantiomers or their racemic mixtures.

4.
Nanoscale Adv ; 5(21): 5923-5931, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37881716

RESUMO

Interactions between graphene, with its wide deployment in consumer products, and skin, the body's largest organ and first barrier, are highly relevant with respect to toxicology and dermal delivery. In this work, interaction of polyglycerol-functionalized graphene sheets, with 200 nm average lateral size and different surface charges, and human skin was studied and their potential as topical delivery systems were investigated. While neutral graphene sheets showed no significant skin interaction, their positively and negatively charged counterparts interacted with the skin, remaining in the stratum corneum. This efficient skin interaction bears a warning but also suggests a new topical drug delivery strategy based on the sheets' high loading capacity and photothermal property. Therefore, the immunosuppressive drug tacrolimus was loaded onto positively and negatively charged graphene sheets, and its release measured with and without laser irradiation using liquid chromatography tandem-mass spectrometry. Laser irradiation accelerated the release of tacrolimus, due to the photothermal property of graphene sheets. In addition, graphene sheets with positive and negative surface charges were loaded with Nile red, and their ability to deliver this cargo through the skin was investigated. Graphene sheets with positive surface charge were more efficient than the negatively charged ones in enhancing Nile red penetration into the skin.

5.
ACS Nano ; 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599026

RESUMO

Piezoelectric nanogenerators (PENGs) provide a viable solution to convert the mechanical energy generated by body movement to electricity. One-dimensional yarns offer a platform for flexible wearable textile PENGs, which can conform to body for comfort and efficient energy harvesting. In this context, we report a flexible piezoelectric yarn, assembled by one-step cocentric deposition of cesium lead halide perovskite decorated polyvinylidene fluoride (PVDF) nanofibers, on a stainless-steel yarn. Perovskite crystals were formed in situ during electrospinning. Our work demonstrates a nanofiber morphology in which perovskite crystals spread over the nanofiber, leading to a rough surface, and complementing piezoelectric nanocomposite formation with PVDF for superior stress excitation. We investigated how the halide anions of perovskite affect the piezoelectric performance of PENG yarns by comparing CsPbBr3 and CsPbI2Br. Effects of the perovskite concentration, annealing temperature, and deposition time on the piezoelectric properties of PENG yarns were investigated. Devices assembled with a single yarn of CsPbI2Br decorated PVDF nanofibers yield the optimal performance with an output voltage of 8.3 V and current of 1.91 µA in response to pressing from an actuator and used to charge capacitors for powering electronics. After aging in the ambient environment for 3 months, the device maintained its performance during 19,200 cycles of mechanical stresses. The excellent and stable electrical performance can be ascribed to the optimized crystallization of CsPbI2Br crystals, their complementing performance with PVDF, and formation of nanofibers with uniformity and strength. The flexibility of piezoelectric yarns enables them to be bent, twisted, braided, and woven for different textile integrations while harvesting energy from body movements, demonstrating the potential for wearable mechanical energy harvesting.

6.
RSC Adv ; 12(36): 23566-23577, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36090422

RESUMO

Since biocatalysts manoeuvre most of the physiological activities in living organisms and exhibit extreme selectivity and specificity, their use to trigger physicochemical change in polymeric architectures has been successfully used for targeted drug delivery. Our major interest is to develop lipase responsive nanoscale delivery systems from bio-compatible and biodegradable building blocks. Herein, we report the synthesis of four novel non-ionic Gemini amphiphiles using a chemo-enzymatic approach. A symmetrical diglycerol has been used as a core that is functionalised with alkyl chains for the creation of a hydrophobic cavity, and for aqueous solubility (polyethylene glycol) monomethyl ether (mPEG) is incorporated. Such systems can exhibit a varied self-assembly behaviour leading to the observance of different morphological structures. The aggregation behaviour of the synthesised nanocarrier was studied by dynamic light scattering (DLS) and critical aggregation concentration (CAC) measurements. The nanotransport potential of amphiphiles was investigated for hydrophobic guest molecules, i.e. Nile red, nimodipine and curcumin. Cytotoxicity of the amphiphiles was studied using HeLa and MCF7 cell lines at different concentrations, i.e. 0.05, 0.1, and 0.5 mg mL-1. All nanocarriers were found to be non-cytotoxic up to a concentration of 0.1 mg mL-1. Confocal laser scanning microscopy (cLSM) study suggested the uptake of encapsulated dye in the cytosol of the cancer cells within 4 h, thus implying that amphiphilic systems can efficiently transport hydrophobic drug molecules into cells. The biomedical application of the synthesised Gemini amphiphiles was also investigated for dermal drug delivery. In addition, the enzyme-mediated release study was performed that demonstrated 90% of the dye is released within three days. All these results supported the capability of nanocarriers in drug delivery systems.

7.
Int J Nanomedicine ; 16: 7137-7151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712046

RESUMO

INTRODUCTION: Rapamycin (Rapa) is an immunosuppressive macrolide that inhibits the mechanistic target of rapamycin (mTOR) activity. Thanks to its anti-proliferative effects towards different cell types, including keratinocytes and T cells, Rapa shows promise in the treatment of skin diseases characterized by cell hyperproliferation. However, Rapa skin penetration is limited due to its lipophilic nature (log P = 4.3) and high molecular weight (MW = 914 g/mol). In previous studies, new microenvironment-sensitive core multishell (CMS) nanocarriers capable of sensing the redox state of inflamed skin were developed as more efficient and selective vehicles for macrolide delivery to inflamed skin. METHODS: In this study, we tested such redox-sensitive CMS nanocarriers using an inflammatory skin model based on human skin explants co-cultured with Jurkat T cells. Serine protease (SP) was applied on skin surface to induce skin barrier impairment and oxidative stress, whereas phytohaemagglutinin (PHA), IL-17A, and IL-22 were used to activate Jurkat cells. Activation markers, such as CD45 and CD69, phosphorylated ribosomal protein S6 (pRP-S6), and IL-2 release were monitored in activated T cells, whereas pro-inflammatory cytokines were measured in skin extracts and culture medium. RESULTS: We found that alteration of skin barrier proteins corneodesmosin (CDSN), occludin (Occl), and zonula occludens-1 (ZO-1) as well as oxidation-induced decrease of free thiol groups occurred upon SP-treatment. All Rapa formulations exerted inhibitory effects on T cells after penetration across ex vivo skin. No effects on skin inflammatory markers were detected. The superiority of the oxidative-sensitive CMS nanocarriers over the other formulations was observed with regard to drug delivery as well as downregulation of IL-2 release. CONCLUSION: Overall, our results demonstrate that nanocarriers addressing features of diseased skin are promising approaches to improve the topical delivery of macrolide drugs.


Assuntos
Nanopartículas , Absorção Cutânea , Administração Cutânea , Anti-Inflamatórios/metabolismo , Técnicas de Cocultura , Dexametasona , Portadores de Fármacos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Sirolimo , Pele/metabolismo
8.
ACS Biomater Sci Eng ; 7(6): 2485-2495, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33905661

RESUMO

A synthetic route for oxidation-sensitive core-multishell (osCMS) nanocarriers was established, and their drug loading and release properties were analyzed based on their structural variations. The nanocarriers showed a drug loading of 0.3-3 wt % for the anti-inflammatory drugs rapamycin and dexamethasone and the photosensitizer meso-tetra-hydroxyphenyl-porphyrin (mTHPP). Oxidative processes of the nanocarriers were probed in vitro by hydrogen peroxide, and the degradation products were identified by infrared spectroscopy supported by ab initio calculations, yielding mechanistic details on the chemical changes occurring in redox-sensitive nanocarriers. Oxidation-triggered drug release of the model drug Nile Red measured and assessed by time-dependent fluorescence spectroscopy showed a release of up to 80% within 24 h. The drug delivery capacity of the new osCMS nanocarriers was tested in ex vivo human skin with and without pretreatments to induce local oxidative stress. It was found that the delivery of mTHPP was selectively enhanced in skin under oxidative stress. The number and position of the thioether groups influenced the physicochemical as well as drug delivery properties of the carriers.


Assuntos
Portadores de Fármacos , Nanopartículas , Dexametasona , Sistemas de Liberação de Medicamentos , Humanos , Oxirredução
9.
Int J Biol Macromol ; 181: 1063-1071, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33892037

RESUMO

Fiber electrodes are the main functional elements of flexible and textile-based storage devices. This study proposes a Polypyrrole (PPy) and MXene composite, grown on cotton fiber, as a high capacitance electrode. Pyrrole (Py) and MXene are processed and deposited along with an in-situ polymerization. The mass and areal capacitance of the assembled (PPy/MXene)@Cotton electrode respectively reach to 506.6 F g-1, at current density of 1 A g-1 and 455.9 mF cm-2 at scan rate of 0.9 mA cm-2. These values outperform the PPy@Cotton fiber electrode, around 45.8% and 119% respectively. As-prepared fiber electrodes with mechanical strength of 107.3 MPa and conductivity of 60.8 S/m, offer intriguing application prospects in the field of weaving and flexible fibrous supercapacitors.


Assuntos
Fibra de Algodão , Polimerização/efeitos dos fármacos , Polímeros/química , Pirróis/química , Têxteis , Capacitância Elétrica , Eletrodos
10.
RSC Adv ; 11(35): 21702-21715, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35478795

RESUMO

We report the synthesis and characterization of graphene functionalized with iron (Fe3+) oxide (G-Fe3O4) nanohybrids for radio-frequency magnetic hyperthermia application. We adopted the wet chemical procedure, using various contents of Fe3O4 (magnetite) from 0-100% for making two-dimensional graphene-Fe3O4 nanohybrids. The homogeneous dispersal of Fe3O4 nanoparticles decorated on the graphene surface combined with their biocompatibility and high thermal conductivity make them an excellent material for magnetic hyperthermia. The morphological and magnetic properties of the nanohybrids were studied using scanning electron microscopy (SEM) and a vibrating sample magnetometer (VSM), respectively. The smart magnetic platforms were exposed to an alternating current (AC) magnetic field of 633 kHz and of strength 9.1 mT for studying their hyperthermic performance. The localized antitumor effects were investigated with artificial neural network modeling. A neural net time-series model was developed for the assessment of the best nanohybrid composition to serve the purpose with an accuracy close to 100%. Six Nonlinear Autoregressive with External Input (NARX) models were obtained, one for each of the components. The assessment of the accuracy of the predicted results has been done on the basis of Mean Squared Error (MSE). The highest Mean Squared Error value was obtained for the nanohybrid containing 45% magnetite and 55% graphene (F45G55) in the training phase i.e., 0.44703, which is where the model achieved optimal results after 71 epochs. The F45G55 nanohybrid was found to be the best for hyperthermia applications in low dosage with the highest specific absorption rate (SAR) and mean squared error values.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 238: 118439, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32387917

RESUMO

A new chemosensor based on the thiazolylazo-quinazolinone hybrid (TAQH) was designed and synthesized for naked-eye sensitive detection of F- and S2-in aqueous acetonitrile solution. Spectral characterization of TAQH using FT-IR, 1H NMR, and 13C NMR analysis revealed that the probe TAQH was successfully synthesized using a two steps reaction, including the diazotization-coupling and condensation reactions, respectively. The ion sensing ability of TAQH toward a wide range of anions and metal ions was evaluated by naked-eye detection method and UV-Vis absorption spectroscopy. The chemosensor TAQH displayed a fast and clear color change from yellow to red in the presence of F- and S2- ions, enabling easily detect with the naked eye. This clear color change is due to the effective interaction of the basic F- and S2- anions with hydroxyl group of chemosensor as a binding site. The experimental data also revealed that the F- and S2- ions were sensed by the probe TAQH over a wide pH range from 3 to 8. The results also confirmed that the TAQH has a wide linear detection range for F- and S2- ions. From UV-vis titration experiment, the limit of detection (LOD) for F- and S2- ions was found to be 3.1 µM and 5.7 µM, respectively. For quantitative measurements, the paper test strips containing TAQH were successfully fabricated and applied to detect F- and S2- ions in aqueous solutions. Furthermore, Job's plot based on spectroscopic data showed one-to-one stoichiometry for the interaction of anions with probe TAQH. Therefore, the proposed chemosensor with excellent features like the cost-effective, high sensitively and selectively and short response times can be utilized in any physical and biological conditions.

12.
Int J Pharm ; 580: 119212, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32165226

RESUMO

A new class of non-ionic amphiphiles have been synthesised using a combination of polyethylene glycol (PEG) and oligoglycerol dendrons as hydrophilic units and an alkoxy aryl moiety as hydrophobic unit. The resulting amphiphiles were found to aggregate in aqueous medium. Their aggregation behaviour was studied using dynamic light scattering (DLS), fluorescence spectroscopy, and cryogenic electron microscopy (cryo-TEM). The inner hydrophobic core of these aggregates in aqueous medium is capable of encapsulating lipophilic guest molecules. The encapsulation behaviour was studied using Nile red as a hydrophobic dye as well as Curcumin and Dexamethasone as hydrophobic drug candidates. Furthermore, for biological evaluation, cytotoxicity and cellular uptake was studied using different cancer cell lines. The biomedical application of synthesised amphiphiles was further investigated for dermal drug delivery on excised human skin using Nile red encapsulated in the nanocarrier. The release profile of drug/dye encapsulated amphiphiles was studied under physiochemical conditions in the presence of immobilized lipase Novozym 435.


Assuntos
Antracenos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Polietilenoglicóis/química , Absorção Cutânea/fisiologia , Células A549 , Antracenos/administração & dosagem , Antracenos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Células HeLa , Humanos , Células MCF-7 , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Técnicas de Cultura de Órgãos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Absorção Cutânea/efeitos dos fármacos
13.
Pharmaceutics ; 13(1)2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33383706

RESUMO

A synthetic route for redox-sensitive and non-sensitive core multi-shell (CMS) carriers with sizes below 20 nm and narrow molecular weight distributions was established. Cyclic voltammetric measurements were conducted characterizing the redox potentials of reduction-sensitive CMS while showcasing its reducibility through glutathione and tris(2-carboxyethyl)-phosphine as a proof of concept. Measurements of reduction-initiated release of the model dye Nile red by time-dependent fluorescence spectroscopy showed a pronounced release for the redox-sensitive CMS nanocarrier (up to 90% within 24 h) while the non-sensitive nanocarriers showed no release in PBS. Penetration experiments using ex vivo human skin showed that the redox-sensitive CMS nanocarrier could deliver higher percentages of the loaded macrocyclic dye meso-tetra (m-hydroxyphenyl) porphyrin (mTHPP) to the skin as compared to the non-sensitive CMS nanocarrier. Encapsulation experiments showed that these CMS nanocarriers can encapsulate dyes or drugs with different molecular weights and hydrophobicity. A drug content of 1 to 6 wt% was achieved for the anti-inflammatory drugs dexamethasone and rapamycin as well as fluorescent dyes such as Nile red and porphyrins. These results show that redox-initiated drug release is a promising strategy to improve the topical drug delivery of macrolide drugs.

14.
Adv Fiber Mater ; 2(3): 123-139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-38624352

RESUMO

Public health events caused by viruses pose a significant risk to humans worldwide. From December 2019 till now, the rampant novel 2019 coronavirus (SAR-CoV-2) has hugely impacted China and over world. Regarding a commendable means of protection, mask technology is relatively mature, though most of the masks cannot effectively resist the viral infections. The key material of the mask is a non-woven material, which makes the barrier of virus through filtration. Due to the lack of the ability to kill the viruses, masks are prone to cross-infection and become an additional source of infection after being discarded. If the filteration and antiviral effects can be simultaneously integrated into the mask, it will be more effcient, work for a longer time and create less difficulty in post-treatment. This mini-review presents the advances in antiviral materials, different  mechanisms of their activity, and their potential applications in personal protective fabrics. Furthermore, the article addresses the future challenges and directions of mask technology.

15.
Biomacromolecules ; 20(5): 1867-1875, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-30995401

RESUMO

Polyglycerol nanogels are three-dimensional polymeric networks with a few hundred nanometer sizes and the ability to encapsulate and deliver cargos for a wide range of biomedical applications. However, time-consuming and multistep synthetic routes as well as milligram-scale production have hindered further development of these nanomaterials. In this work, we report on a straightforward synthetic method for the production of polyglycerol nanoarchitectures. Enzymatic ring-opening copolymerization of a mixture of glycidol and succinic anhydride resulted in polyglycerol nanogels with succinic acid segments in their backbone. Novozyme 435 was used as a dual catalytic agent to support ring-opening polymerization of the above-mentioned cyclic monomers as well as esterification of the produced oligomers to obtain nanogels. While succinic acid segments improved the biodegradability and loading capacity of nanogels, polyglycerol caused water solubility, high functionality, and biocompatibility. Nanogels were loaded with tacrolimus and photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP)-a close congener of the approved photosensitizer temoporfin (mTHPC)-and their ability to improve the skin penetration of these therapeutic agents was investigated. mTHPP delivery experiments on human skin, which were quantified by fluorescence microscopy, showed that these nanogels deposit in the stratum corneum and release the loaded drug to viable epidermis of skin efficiently in comparison with commercially available base cream. Taking advantage of the straightforward synthesis as well as biodegradability, biocompatibility, high loading capacity, and efficient skin penetration, the synthesized nanogels could be used as future topical delivery systems.


Assuntos
Portadores de Fármacos , Glicerol/síntese química , Nanogéis/química , Polímeros/síntese química , Absorção Cutânea , Succinatos/síntese química , Administração Cutânea , Sistemas de Liberação de Medicamentos
16.
J Control Release ; 300: 64-72, 2019 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-30797001

RESUMO

Nanogels that are assembled by supramolecular interactions as compared to covalent crosslinked nanogels, exhibit new functionalities with potential for easy processability, recycling and self-healing due to the nature of dynamic and reversible non-covalent interactions. Here we design a supramolecular polymer nanogel that utilize host-guest interactions between the groups pillar [5] arene and alkyl chains on hyperbranched polyglycerol backbone as crosslinking agents for a new dermal drug delivery system. The anti-inflammatory drug Dexamethasone (Dexa) can be efficiently loaded into the nanogels and released from the assemblies. Besides, the supramolecular polymer nanogels exhibit better drug loading capacity and skin penetration enhancement than the individual host polymer and guest polymer. In vitro skin permeation studies show that supramolecular polymer nanogels can improve the Nile red penetration through the skin by up to 9 fold, compared to the individual polymers or a conventional cream formulation on a barrier deficient skin model.


Assuntos
Sistemas de Liberação de Medicamentos , Nanogéis/administração & dosagem , Administração Cutânea , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Calixarenos/administração & dosagem , Calixarenos/química , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/administração & dosagem , Dexametasona/química , Liberação Controlada de Fármacos , Glicerol/administração & dosagem , Glicerol/química , Humanos , Oxazinas/administração & dosagem , Oxazinas/química , Polímeros/administração & dosagem , Polímeros/química , Pele/metabolismo
17.
Nanoscale ; 10(35): 16848-16856, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30168550

RESUMO

Due to the low cutaneous bioavailability of tacrolimus (TAC), penetration enhancers are used to improve its penetration into the skin. However, poor loading capacity, non-biodegradability, toxicity, and in some cases inefficient skin penetration are challenging issues that hamper their applications for the dermal TAC delivery. Here we present poly(lactide-co-glycerol) (PLG) as a water soluble, biodegradable, and biocompatible TAC-carrier with high loading capacity (14.5% w/w for TAC) and high drug delivery efficiencies into the skin. PLG was synthesized by cationic ring-opening copolymerization of a mixture of glycidol and lactide and showed 35 nm and 300 nm average sizes in aqueous solutions before and after loading of TAC, respectively. Delivery experiments on human skin, quantified by fluorescence microscopy and LC-MS/MS, showed a high ability for PLG to deposit Nile red and TAC into the stratum corneum and viable epidermis of skin in comparison with Protopic® (0.03% w/w, TAC ointment). The cutaneous distribution profile of delivered TAC proved that 80%, 16%, and 4% of the cutaneous drug level was deposited in the stratum corneum, viable epidermis, and upper dermis, respectively. TAC delivered by PLG was able to efficiently decrease the IL-2 and TSLP expressions in human skin models. Taking advantage of the excellent physicochemical and biological properties of PLG, it can be used for efficient dermal TAC delivery and potential treatment of inflammatory skin diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Absorção Cutânea , Tacrolimo/administração & dosagem , Administração Cutânea , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Humanos , Técnicas In Vitro , Inflamação/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Dermatopatias/tratamento farmacológico
18.
Nanoscale ; 10(18): 8526-8535, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29694485

RESUMO

Perovskite solar cells (PSCs) have gained great interest, owing to a fast increase in their power conversion efficiency (PCE), within a few years. However, their wide application and scale-up are hampered due to multiple obstacles, such as chemical instability, which leads to a short lifetime, and their complicated reaction and crystallization, which requires thermal annealing. Here, we address these issues using the ultrasonic substrate vibration post treatment (SVPT) applied on the as-spun perovskite wet films, so as to achieve a uniform, microscale and stable mixed-halide and mixed-cation perovskite layer, (FAPbI3)0.85(MAPbBr3)0.15, without the need for a conventional thermal annealing step. This is achieved by the creation of fluid micromixing and in situ annealing within the solution, caused by the ultrasonic excitation of the wet film. The optoelectronic properties of the perovskite films subjected to the SVPT, including photoemission, carrier lifetime and band gap, are remarkably improved compared to the conventionally annealed films. When incorporated into a planar PSC, a maximum PCE of 18.55% was achieved, compared to 15.17% for the control device, with high reproducibility and no hysteresis, and the device retained 80% of its initial PCE, over a period of 20 days of storage under ambient conditions.

19.
Nanoscale Res Lett ; 11(1): 408, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27639581

RESUMO

In this paper, two-step sequential spin-dip and spin-spin coating, as well as one-step spin coating, methods are used to fabricate methylammonium lead mixed-halide perovskites to study the effect of process parameters, including the choice of the solvent, annealing temperature, spin velocity, and dipping time on the characteristics of the perovskite film. Our results show that using a mixture of DMF and DMSO, with volume ratio of 1:1, as the organic solvents for PbCl2 results in the best mixed-halide perovskite because of the effective coordination between DMSO and PbCl2. Surface dewetting due to two effects, i.e., crystallization and thin liquid film instability, is observed and discussed, where an intermediate spin velocity of about 4000 rpm is found suitable to suppress dewetting. The perovskite film fabricated using the one-step method followed by anti-solvent treatment shows the best perovskite conversion in XRD patterns, and the planar device fabricated using the same method exhibited the highest efficiency among the employed methods. The perovskite layer made by sequential spin-dip coating is found thicker with higher absorbance, but the device shows a lower efficiency because of the challenges associated with perovskite conversion in the sequential method. The one-step deposition method is found easier to control and more promising than the sequential deposition methods.

20.
J Control Release ; 242: 35-41, 2016 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-27469470

RESUMO

Nanogels offer many unique features rendering them as very attractive candidates for drug delivery. However, for their applications the loading capacity and specific encapsulation, in particular for hydrophobic drugs, in a complex media are two critical factors. In this work, we report for the first time on the preparation of nanogel-peptide conjugates with the ability of specific encapsulation of temoporfin (m-THPC). The peptide was selected based on combinatorial means and it was conjugated to polyglycerol as the nanogel precursor. We observed that the loading capacity of nanogels improved 16 times upon peptide conjugation. Skin penetrations tests in barrier deficient skin showed that nanogel-peptide conjugates enhance the penetration of m-THPC in the viable skin layers efficiently. This study indicates that nanogel-peptide conjugates could be used as unique carriers with high loading capacity for hydrophobic compounds, which provides the basis for the design of advanced topical drug delivery systems.


Assuntos
Sistemas de Liberação de Medicamentos , Mesoporfirinas/administração & dosagem , Nanopartículas , Absorção Cutânea , Administração Cutânea , Portadores de Fármacos/química , Glicerol/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Mesoporfirinas/farmacocinética , Peptídeos/química , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacocinética , Polímeros/química
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