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1.
Int J Mol Sci ; 25(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38892121

RESUMEN

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.


Asunto(s)
Cannabidiol , Hidrogeles , Piel , Hidrogeles/química , Hidrogeles/farmacología , Cannabidiol/farmacología , Cannabidiol/química , Piel/efectos de los fármacos , Piel/metabolismo , Humanos , Monoterpenos Ciclohexánicos/química , Monoterpenos Ciclohexánicos/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Regeneración/efectos de los fármacos , Polímeros/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Queratinocitos/efectos de los fármacos , Células HaCaT , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Antiinfecciosos/farmacología , Antiinfecciosos/química
2.
Int J Mol Sci ; 24(8)2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37108074

RESUMEN

The aim of this study was to develop an innovative, dual-stimuli-responsive smart hydrogel local drug delivery system (LDDS), potentially useful as an injectable simultaneous chemotherapy and magnetic hyperthermia (MHT) antitumor treatment device. The hydrogels were based on a biocompatible and biodegradable poly(ε-caprolactone-co-rac-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-rac-lactide) (PCLA-PEG-PCLA, PCLA) triblock copolymer, synthesized via ring-opening polymerization (ROP) in the presence of a zirconium(IV) acetylacetonate (Zr(acac)4) catalyst. The PCLA copolymers were successfully synthesized and characterized using NMR and GPC techniques. Furthermore, the gel-forming and rheological properties of the resulting hydrogels were thoroughly investigated, and the optimal synthesis conditions were determined. The coprecipitation method was applied to create magnetic iron oxide nanoparticles (MIONs) with a low diameter and a narrow size distribution. The magnetic properties of the MIONs were close to superparamagnetic upon TEM, DLS, and VSM analysis. The particle suspension placed in an alternating magnetic field (AMF) of the appropriate parameters showed a rapid increase in temperature to the values desired for hyperthermia. The MIONs/hydrogel matrices were evaluated for paclitaxel (PTX) release in vitro. The release was prolonged and well controlled, displaying close to zero-order kinetics; the drug release mechanism was found to be anomalous. Furthermore, it was found that the simulated hyperthermia conditions had no effect on the release kinetics. As a result, the synthesized smart hydrogels were discovered to be a promising antitumor LDDS, allowing simultaneous chemotherapy and hyperthermia treatment.


Asunto(s)
Hidrogeles , Nanopartículas de Magnetita , Hidrogeles/química , Poliésteres/química , Polietilenglicoles/química , Polímeros/química , Sistemas de Liberación de Medicamentos , Temperatura
3.
Materials (Basel) ; 15(24)2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36556694

RESUMEN

The aim of this work was to obtain and characterize composite biomaterials containing two components, namely carbonated hydroxyapatite, which was substituted with Mg2+ and Zn2+ ions, and natural polymer-collagen protein. The following two different types of collagen were used: lyophilized powder of telocollagen from bovine Achilles tendon and atelocollagen solution from bovine dermis. The obtained 3D materials were used as potential matrices for the targeted delivery of tranexamic acid for potential use in wound healing after tooth extractions. Tranexamic acid (TXA) was introduced into composites by two different methods. The physicochemical analyses of the obtained composites included Fourier-transform infrared spectroscopy (FT-IR), inductively coupled plasma-optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), release kinetics tests, swelling test, and cytotoxicity assays. The studies showed that the proposed synthetic methods yielded biomaterials with favorable physicochemical properties, as well as the expected release profile of the drug and ions from the matrices.

4.
Int J Mol Sci ; 23(22)2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36430222

RESUMEN

Thermosensitive liquid suppositories (LSs) carrying the model antihypertensive drug metoprolol tartrate (MT) were developed and evaluated. The fundamental purpose of this work was to produce, for the first time, liquid MT suppositories based on biodegradable nanoparticles and optimize their rheological and mechanical properties for prospective rectal administration. The nanoparticle system was based on a biodegradable copolymer synthesized by ring opening polymerization (ROP) of glycolide (GL) and L,L-lactide (LLA). Biodegradable nanoparticles loaded with the model drug were produced by the o/o method at the first stage of the investigation. Depending on the concentration of the drug in the sample, from 66 to 91% of MT was released over 12 h, according to first-order kinetics. Then, thermosensitive LSs with MT-loaded biodegradable nanoparticles were obtained by a cold method and their mechanical and rheological properties were evaluated. To adjust the thermogelling and mucoadhesive properties for rectal administration, the amounts of major formulation components such as poloxamers (P407, P188), Tween 80, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and sodium alginate were optimized. The in vitro release results revealed that more than 80% of the MT was released after 12 h, following also first-order kinetics. It was discovered that the diffusion process was dominant. The drug release profile was mainly governed by the rheological and mechanical properties of the developed formulation. Such a novel, thermosensitive formulation might be an effective alternative to hypertension treatment, particularly for unconscious patients, patients with mental illnesses, geriatric patients, and children.


Asunto(s)
Metoprolol , Nanopartículas , Niño , Humanos , Anciano , Supositorios , Poliglactina 910 , Estudios Prospectivos
5.
Int J Mol Sci ; 23(13)2022 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-35806116

RESUMEN

The aim of the current work was to study the physicochemical properties and biological activity of different types of porous granules containing silver or gallium ions. Firstly, hydroxyapatites powders doped with Ga3+ or Ag+ were synthesized by the standard wet method. Then, the obtained powders were used to fabricate ceramic microgranules (AgM and GaM) and alginate/hydroxyapatite composite granules (AgT and GaT). The ceramic microgranules were also used to prepare a third type of granules (AgMT and GaMT) containing silver or gallium, respectively. All the granules turned out to be porous, except that the AgT and GaT granules were characterized by higher porosity and a better developed specific surface, whereas the microgranules had very fine, numerous micropores. The granules revealed a slow release of the substituted ions. All the granules except AgT were classified as non-cytotoxic according to the neutral red uptake (NRU) test and the MTT assay. The obtained powders and granules were subjected to various antibacterial test towards the following four different bacterial strains: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli. The Ag-containing materials revealed high antibacterial activity.


Asunto(s)
Sustitutos de Huesos , Galio , Antibacterianos/química , Antibacterianos/farmacología , Durapatita/química , Escherichia coli , Galio/farmacología , Iones , Polvos , Plata/química , Plata/farmacología
6.
Molecules ; 27(3)2022 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-35164403

RESUMEN

Aliphatic polyesters are the most common type of biodegradable synthetic polymer used in many pharmaceutical applications nowadays. This report describes the ring-opening polymerization (ROP) of l-lactide (L-LA), ε-caprolactone (CL) and glycolide (Gly) in the presence of a simple, inexpensive and convenient PEG200-BiOct3 catalytic system. The chemical structures of the obtained copolymers were characterized by 1H- or 13C-NMR. GPC was used to estimate the average molecular weight of the resulting polyesters, whereas TGA and DSC were employed to determine the thermal properties of polymeric products. The effects of temperature, reaction time, and catalyst content on the polymerization process were investigated. Importantly, the obtained polyesters were not cyto- or genotoxic, which is significant in terms of the potential for medical applications (e.g., for drug delivery systems). As a result of transesterification, the copolymers obtained had a random distribution of comonomer units along the polymer chain. The thermal analysis indicated an amorphous nature of poly(l-lactide-co-ε-caprolactone) (PLACL) and a low degree of crystallinity of poly(ε-caprolactone-co-glycolide) (PCLGA, Xc = 15.1%), in accordance with the microstructures with random distributions and short sequences of comonomer units (l = 1.02-2.82). Significant differences in reactivity were observed among comonomers, confirming preferential ring opening of L-LA during the copolymerization process.


Asunto(s)
Bismuto/química , Caproatos/química , Dioxanos/química , Lactonas/química , Ácido Poliglicólico/química , Polimerizacion , Caproatos/síntesis química , Catálisis , Dioxanos/síntesis química , Lactonas/síntesis química , Poliésteres/síntesis química , Poliésteres/química , Ácido Poliglicólico/síntesis química , Temperatura
7.
Int J Mol Sci ; 22(15)2021 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-34361098

RESUMEN

In this paper, injectable, thermosensitive smart hydrogel local drug delivery systems (LDDSs) releasing the model antitumour drug 5-fluorouracil (5-FU) were developed. The systems were based on biodegradable triblock copolymers synthesized via ring opening polymerization (ROP) of ε-caprolactone (CL) in the presence of poly(ethylene glycol) (PEG) and zirconium(IV) acetylacetonate (Zr(acac)4), as co-initiator and catalyst, respectively. The structure, molecular weight (Mn) and molecular weight distribution (D) of the synthesized materials was studied in detail using nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques; the optimal synthesis conditions were determined. The structure corresponded well to the theoretical assumptions. The produced hydrogels demonstrated a sharp sol-gel transition at temperature close to physiological value, forming a stable gel with good mechanical properties at 37 °C. The kinetics and mechanism of in vitro 5-FU release were characterized by zero order, first order, Higuchi and Korsmeyer-Peppas mathematical models. The obtained results indicate good release control; the kinetics were generally defined as first order according to the predominant diffusion mechanism; and the total drug release time was approximately 12 h. The copolymers were considered to be biodegradable and non-toxic; the resulting hydrogels appear to be promising as short-term LDDSs, potentially useful in antitumor therapy.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Materiales Biocompatibles/administración & dosificación , Sistemas de Liberación de Medicamentos , Fibroblastos/efectos de los fármacos , Fluorouracilo/administración & dosificación , Hidrogeles/administración & dosificación , Temperatura , Animales , Materiales Biocompatibles/química , Proliferación Celular , Células Cultivadas , Fibroblastos/citología , Hidrogeles/síntesis química , Ratones
8.
Drug Chem Toxicol ; 44(2): 140-147, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30574814

RESUMEN

Shikonin (SH) is used as a red pigment for food coloring and cosmetics, and has cytotoxic activity towards cancer cells. However, due to strong toxicity SH has limited potential as an anticancer drug. Acetylshikonin (ASH) is one of the SH derivatives with promising anticancer potential. In present study, we attempted to evaluate and compare the cytotoxicity of SH and ASH towards a normal cell line (V79) and in addition to evaluate their antigenotoxic activity. The evaluation was made with the use of the set of cytotoxicity assays with V79 line and the micronucleus test in vitro performed using clinafloxacin (CLFX), ethyl methanesulfonate (EMS) as direct genotoxins and cyclophosphamide (CPA) as indirect genotoxin. For CPA and EMS the simultaneous protocol was used and for CLFX three different variants were performed: pretreatment, simultaneous, and post-treatment. A higher cytotoxic effect was observed for SH. The EC50 values obtained for SH were approximately twofold lower compared to that of ASH. Moreover, ASH exhibited an antigenotoxic potential against CPA-induced genotoxicity, whereas SH has no activity. However, ASH increased the EMS-induced genotoxicity, when SH exhibited no effect. Both compounds decreased the genotoxicity of CLFX in pretreatment and simultaneous protocol. Based on the results of the present study it can be concluded that ASH is less cytotoxic than SH to normal cells and has comparable antigenotoxic potential.


Asunto(s)
Antraquinonas/farmacología , Daño del ADN/efectos de los fármacos , Naftoquinonas/farmacología , Animales , Antraquinonas/toxicidad , Línea Celular , Cricetulus , Ciclofosfamida/toxicidad , Metanosulfonato de Etilo/toxicidad , Fluoroquinolonas/toxicidad , Pruebas de Micronúcleos , Naftoquinonas/toxicidad
9.
Molecules ; 27(1)2021 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-35011416

RESUMEN

Hairy root cultures are considered as a valuable source of bioactive phytoconstituents with expanding applicability for their production. In the present study, hairy root cultures of Polyscias filicifolia (Araliaceae), a traditional Southeast Asian medicinal plant, were established. The transformation with Agrobacterium rhizogenes ATCC 15834 allowed to obtain 15 root lines. The K-1 line, demonstrating the highest growth capabilities, was subjected to further investigations. To enhance the biosynthetic potential of hairy roots, methyl jasmonate elicitation approach was applied (MeJA; at different doses and exposure time), with subsequent transfer of elicited roots to control medium. This strategy resulted in chlorogenic acid production up to 1.59 mg/g dry weight. HPLC-PDA-ESI-MS analysis demonstrated variation in extracts composition and allowed to identify different caffeic and ferulic acid derivatives. Next, cytotoxic, antigenotoxic, and anti-photogenotoxic properties of hairy roots extracts were determined. None of the tested extracts were cytotoxic. In addition, they demonstrated significant antigenotoxic activity with the highest protective potential; up to 52% and 49% of inhibition of induction ratio (IR) induced by the 2-aminoanthracene was revealed for extracts derived from hairy roots elicited for 3 days with 50 µM MeJA and roots elicited for 7 days with 100 µM MeJA and then transferred for 30 days to control medium, respectively. These same extracts exhibited the highest anti-photogenotoxic potential, up to 36% of inhibition of chloropromazine-induced genotoxicity.


Asunto(s)
Araliaceae/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Sustancias Protectoras/farmacología , Cromatografía Líquida de Alta Presión , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Relación Dosis-Respuesta a Droga , Espectrometría de Masas , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/crecimiento & desarrollo , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Protectores contra Radiación/química , Protectores contra Radiación/farmacología , Espectrometría de Masa por Ionización de Electrospray
10.
Int J Mol Sci ; 21(14)2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32679901

RESUMEN

Hydroxyapatite (HA) powders enriched with silver or gallium ions or both were synthesized by two different routes: standard precipitation and the solid-state method. The powders were characterized by using several methods: inductively coupled plasma optical emission spectrometry (ICP-OES), powder X-ray diffractometry (PXRD), transmission electron microscopy (TEM), infrared spectroscopy (FT-IR) and solid-state nuclear magnetic resonance spectroscopy (ssNMR). The effects of enrichment of the HAs in Ag+ or Ga3+ or both on in vitro cytotoxicity and microbiological activity were discussed. PXRD experiments showed that the samples obtained by the wet method consisted of single-phase nanocrystalline HA, while the samples prepared via the solid-state method are microcrystalline with a small amount of calcium oxide. The introduction of higher amounts of silver ions was found to be more effective than enriching HA with small amounts of Ag+. Gallium and silver ions were found not to affect the lattice parameters. Ga3+ affected the crystallinity of the samples as well as the content of structural hydroxyl groups. Among samples synthesized by the wet method, only one (5Ag-HAw) was cytotoxic, whereas all Ga-containing samples obtained by the dry method showed cytotoxicity. In the preliminary antimicrobial test all the materials containing "foreign" ions showed high antibacterial activity.


Asunto(s)
Antibacterianos/química , Durapatita/química , Galio/química , Plata/química , Animales , Antibacterianos/farmacología , Células 3T3 BALB , Cationes/química , Cationes/farmacología , Durapatita/farmacología , Galio/farmacología , Ratones , Pseudomonas fluorescens/efectos de los fármacos , Plata/farmacología
11.
Pharmaceutics ; 12(6)2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-32486203

RESUMEN

Polymer-drug conjugates are currently being more widely investigated for the treatment of hypertension. In view of the above, in the first stage of our work, we used nontoxic ß-cyclodextrin (ß-CD) as effective, simple, inexpensive, and safe for the human body initiator for the synthesis of biocompatible and biodegradable functionalized polymers suitable for the medical and pharmaceutical applications. The obtained polymeric products were synthesized through a ring-opening polymerization (ROP) of ε-caprolactone (CL), d,l-, and l,l- lactide (LA and LLA). The chemical structures of synthesized materials were elucidated based on 1H NMR and solid-state carbon-13 cross-polarization/magic angle spinning nuclear magnetic resonance (13C CP/MAS NMR) analysis, while the incorporation of ß-CD molecule into the polymer chain was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Furthermore, molecular modeling has been applied to investigate the intrachain rigidities and chain architectures for several representative structures. The obtained and thoroughly characterized branched matrices were then used to generate the first ß-cyclodextrin/biodegradable polymer/ß-blocker conjugate through the successful conjugation of pindolol. The conjugates were fabricated by carbodiimide-mediated coupling reaction. The branched biodegradable materials released the drug in vitro in a sustained manner and without "burst release" and thus have the ability to treat different heart diseases.

12.
Molecules ; 25(5)2020 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-32121158

RESUMEN

Traditional medicinal plants are an important source of active compounds with potential antimutagenic activity. Polyscias filicifolia Bailey (Araliaceae) is a South Asian traditional herb used as an adaptogenic and cardiac drug. Extracts of P. filicifolia contain a wide range of biologically active compounds like phenolic acids and triterpenoid saponins. In the present study. antigenotoxic potential of three naturally occurring phenolic acids and extracts of P. filicifolia growing in vitro with the addition of elicitors was evaluated against direct (4-nitroquinoline-N-oxide (4NQO) and mitomycin C (MMC)) and indirect mutagens (2-aminoanthracene (2AA)). The evaluation was made using a bacterial umu-test. Moreover, the ability to prevent photogenotoxicity induced by chlorpromazine (CPZ) under UVA irradiation was measured. The phytochemical profiling of examined extracts revealed the presence of numerous compounds with the prevelance of chlorogenic, caffeic, and ferulic acid derivatives; however, saponin fractions were also determined. The antioxidant potential of extracts strictly correlated with their composition. The tested extracts exhibited high antigenotoxic activity if the assay was performed with 2AA and metabolic activation. Moreover, the extracts slightly decreased the MMC-induced genotoxicity. However, an increase of the genotoxic effect was observed in the assay performed with 4NQO. In addition, photo-antigenotoxic activity was observed. In our study, phenolic acids exhibited lower activity than the extracts.


Asunto(s)
Antimutagênicos/farmacología , Antioxidantes/farmacología , Araliaceae/química , Daño del ADN , Extractos Vegetales/farmacología , Brotes de la Planta/química , Animales , Antimutagênicos/química , Antioxidantes/química , Clorpromazina/efectos adversos , Clorpromazina/farmacología , Masculino , Mitomicina/efectos adversos , Mitomicina/farmacología , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley
13.
Int J Mol Sci ; 19(12)2018 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-30558119

RESUMEN

In this study, a novel biomaterial, i.e., brushite containing 0.67 wt% of selenium (Se-Bru) was synthesized via a wet precipitation method. Pure, unsubstituted brushite (Bru) was synthesized via the same method and used as a reference material. Different techniques of instrumental analysis were applied to investigate and compare physicochemical properties of both materials. Fourier-Transform Infrared Spectroscopy confirmed the chemical identity of both materials. Scanning Electron Microscopy (SEM) was used to study the morphology and indicated that both samples (Bru and Se-Bru) consisted of plate-like microcrystals. Powder X-ray Diffraction (PXRD) showed that Bru, as well as Se-Bru were crystallographically homogenous. What is more, the data obtained from PXRD studies revealed that the substitution of selenite ions into the crystal structure of the material had clearly affected its lattice parameters. The incorporation of selenium was also confirmed by solid-state ¹H→31P CP MAS kinetics experiments. Additionally, studies on the release kinetics of the elements forming Se-Bru and preliminary cytotoxicity tests were conducted. This preliminary research will favor a better understanding of ionic substitution in calcium phosphates and may be a starting point for the development of selenium-doped brushite cements for potential use in bone tissue impairments treatment.


Asunto(s)
Sustitutos de Huesos/síntesis química , Fosfatos de Calcio/síntesis química , Selenio/química , Animales , Células 3T3 BALB , Sustitutos de Huesos/química , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Supervivencia Celular , Precipitación Química , Ratones , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , Ingeniería de Tejidos , Difracción de Rayos X
14.
Polymers (Basel) ; 10(5)2018 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-30966523

RESUMEN

Antimicrobial peptides (AMPs) are prospective therapeutic options for treating multiple-strain infections. However, clinical and commercial development of AMPs has some limitations due to their limited stability, low bioavailability, and potential hemotoxicity. The purpose of this study was to develop new polymeric carriers as highly controlled release devices for amphibian peptides citropin 1.1 (CIT) and temporin A (TEMP). The release rate of the active pharmaceutical ingredients (APIs) was strongly dependent on the API characteristics and the matrix microstructure. In the current work, we investigated the effect of the polymer microstructure on in vitro release kinetics of AMPs. Non-contact laser profilometry, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) were used to determine the structural changes during matrix degradation. Moreover, geno- and cytotoxicity of the synthesized new carriers were evaluated. The in vitro release study of AMPs from the obtained non-toxic matrices shows that peptides were released with near-zero-order kinetics. The peptide "burst release" effect was not observed. New devices have reached the therapeutic concentration of AMPs within 24 h and maintained it for 28 days. Hence, our results suggest that these polymeric devices could be potentially used as therapeutic options for the treatment of local infections.

15.
J Photochem Photobiol B ; 178: 201-210, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29156348

RESUMEN

The development of innovative solutions in photosafety of photolabile pharmaceutical products may help to reduce the adverse effects of these products, caused by light exposure. Providing new data in this area of study is particularly important in case of drugs applied topically on sensitive organs such as eyes. The main goal of this research is to investigate whether two potential excipients, namely: p-coumaric acid and benzophenone-4, affect the photodegradation, phototoxicity and photogenotoxicity of water solutions of four fluoroquinolones: ciprofloxacin, lomefloxacin, fleroxacin and clinafloxacin. We conducted a set of bioassays combined with the application of high-performance liquid chromatography and mass spectrometry techniques. The significant reduction of phototoxic and photogenotoxic abilities was evaluated in mixtures with ciprofloxacin and p-coumaric acid by using the umu test with Salmonella typhimurium TA1535/pSK1002, the methylthiazol tetrazolium reduction assay, and the micronucleus assay with the V79 cell line. In the bacterial assay the opposite effect was observed for the formulation with lomefloxacin and p-coumaric acid. This may be explained by the significant differences in the profile of the lomefloxacin photodegradation products. Further, the photoprotective and antiphotomutagenic abilities of ciprofloxacin mixed with benzophenone-4 were assessed. Promising results obtained in compositions with ciprofloxacin may be a basis for further research. Nevertheless, the increase in the DNA damage potential in mixtures with p-coumaric acid and two other antibiotics shows the importance of the safety evaluation of such innovative combinations.


Asunto(s)
Composición de Medicamentos , Fluoroquinolonas/química , Sustancias Protectoras/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Ácidos Cumáricos , Cricetinae , Cricetulus , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Fleroxacino/química , Fleroxacino/toxicidad , Fluoroquinolonas/toxicidad , Pruebas de Micronúcleos , Fotólisis/efectos de los fármacos , Fotólisis/efectos de la radiación , Propionatos/química , Sustancias Protectoras/farmacología , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Rayos Ultravioleta
16.
Pharm Res ; 34(4): 780-792, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28120174

RESUMEN

PURPOSE: The purpose of this study was to develop the perspective biodegradable poly(ester-urethane) (PUR) carriers based on "predominantly isotactic" and atactic polylactides (PLAs), and poly(ε-caprolactone) (PCL), for the controlled release of epirubicin (EPI). METHODS: The biodegradable PURs containing different soft segments as new and effective carriers of EPI have been obtained. The preliminary studies on toxicity and degradation of obtained polymers, and the release of the EPI from PUR carriers were carried out. RESULTS: We found that the kinetic release of EPI from the obtained PUR carriers tested in vitro at 37°C and pH 7.4 was strongly dependent on the kind of the polyesters, used as the soft segment in PURs synthesis. Furthermore, we demonstrated that the EPI was released from various synthesized carriers in a rather regular manner, according to the diffusion-degradation and degradation mechanisms. Importantly, in some cases, the kinetics of the EPI release was nearly zero-order. CONCLUSION: The results show that the obtained PURs are very effective and perspective carriers and might be potentially applied in the technology of high controlled EPI delivery systems.


Asunto(s)
Antineoplásicos/química , Portadores de Fármacos/química , Epirrubicina/química , Poliésteres/química , Poliuretanos/química , Materiales Biocompatibles , Preparaciones de Acción Retardada , Portadores de Fármacos/síntesis química , Liberación de Fármacos , Poliésteres/síntesis química , Poliuretanos/síntesis química
17.
Toxicol In Vitro ; 30(1 Pt B): 364-72, 2015 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-26434532

RESUMEN

The aim of this study was to evaluate the antigenotoxic and antioxidant potential of shikonin (SH), acetylshikonin (ACS) and Arnebia euchroma callus extract (EXT). The antigenotoxic activity was investigated by the umu-test as the inhibition of the SOS system induction caused by genotoxic chemical agents - 4-nitroquinoline oxide and 2-aminoanthracene. Moreover the ability of SH, ACS and EXT to prevent photogenotoxicity triggered by chlorpromazine under UVA irradiation was measured. The cytotoxicity of EXT toward V79 Chinese hamster cell line was additionally assessed. Shikonin and acetylshikonin had no effect on 4-NQO induced genotoxicity whereas EXT demonstrated an unclear effect. The protection against 2AA induced genotoxicity was observed for all tested substances. The highest protection was demonstrated for EXT with inhibition of 66%. SH and ACS reduced 2AA genotoxicity with inhibition of about 60%. Under UVA the strongest and dose-dependent activity was observed for EXT. Acetylshikonin was a weak anti-photogenotoxin whereas shikonin had no clear effect. EXT was highly cytotoxic toward the V79 cell line - the cells' morphology was affected seriously and apoptosis was impacted. The antioxidant activity of SH, ACS and EXT was studied by means of electron paramagnetic resonance spectroscopy using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. All three samples exhibited radical scavenging properties.


Asunto(s)
Antraquinonas/farmacología , Antioxidantes/farmacología , Boraginaceae , Espectroscopía de Resonancia por Spin del Electrón/métodos , Naftoquinonas/farmacología , Extractos Vegetales/farmacología , 4-Nitroquinolina-1-Óxido/toxicidad , Animales , Antracenos/toxicidad , Línea Celular , Clorpromazina/toxicidad , Cricetinae , Cricetulus , Masculino , Pruebas de Mutagenicidad , Ratas , Ratas Sprague-Dawley
18.
J Photochem Photobiol B ; 144: 76-84, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25728226

RESUMEN

Fluoroquinolones are widely used anti-bacterial agents that are known to exhibit moderate to severe phototoxicity. Furthermore some of them reveal photogenotoxicity under UV irradiation. Incidence of side effects due to light exposure may be augmented, if the medicament is used topically. The main goal of this work was to compare the extent of photodegradation of ofloxacin in ointments with various excipients: hydrated or non-hydrated base and the addition of sunscreens: bisoctrizole (Tinosorb M) and bemotrizinol (Tinosorb S). The next goal of present work was the analysis of phototoxicity and photogenotoxicity of ofloxacin photodegradation products in tested ointments and in solutions with the umu-test, the test of mitotic gene conversion with Saccharomyces cerevisiae D7 and the micronucleus assay with V79 Chinese hamster cell line. At the same time an attempt was made to determinate the photodegradation products of ofloxacin in different unguents variants. We observed a significant photoprotective effect in ointment with Tinosorb M. We did not evaluated relevant differences regarding the genotoxicity and toxicity of unguents. However, the pre-irradiated ofloxacin solutions in comparison to samples stored in the dark were significantly more genotoxic to bacteria, slightly increased the number of micronuclei in V79 cell line and were toxic to the yeast strain.


Asunto(s)
Ofloxacino/química , Ofloxacino/toxicidad , Pomadas/química , Fotólisis , Protectores Solares/química , Rayos Ultravioleta , Animales , Línea Celular , Cricetulus , Conversión Génica/efectos de los fármacos , Conversión Génica/efectos de la radiación , Pruebas de Micronúcleos , Mutágenos/química , Mutágenos/toxicidad , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/efectos de la radiación , Soluciones , Agua/química
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