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Article: Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel.

Lajarin-Reinares, Maria / Naveira-Souto, Iria / Mallandrich, Mireia / Suñer-Carbó, Joaquim / Llagostera Casas, Montserrat / Calvo, Maria Angels / Fernandez-Campos, Francisco

Pharmaceutics

2023 Volume 15, Issue 5

Abstract: Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative ... ...

Abstract	Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative to treat vaginal candidiasis. The aim of the current study was to develop and optimize a mucoadhesive drug delivery system for the local administration of disulfiram. Such formulations were composed of polyethylene glycol and carrageenan to improve the mucoadhesive and mechanical properties and to prolong the residence time in the vaginal cavity. Microdilution susceptibility testing showed that these gels had antifungal activity against
Language	English
Publishing date	2023-05-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15051436
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Article ; Online: Hydrogel of Thyme-Oil-PLGA Nanoparticles Designed for Skin Inflammation Treatment.

Folle, Camila / Díaz-Garrido, Natalia / Mallandrich, Mireia / Suñer-Carbó, Joaquim / Sánchez-López, Elena / Halbaut, Lyda / Marqués, Ana M / Espina, Marta / Badia, Josefa / Baldoma, Laura / Calpena, Ana Cristina / García, Maria Luisa

Gels (Basel, Switzerland)

2024 Volume 10, Issue 2

Abstract: Thyme oil (THO) possesses excellent antibacterial and antioxidant properties which are suitable for skin inflammatory disorders such as acne vulgaris. However, THO is insoluble in water and its components are highly volatile. Therefore, these drawbacks ... ...

Abstract	Thyme oil (THO) possesses excellent antibacterial and antioxidant properties which are suitable for skin inflammatory disorders such as acne vulgaris. However, THO is insoluble in water and its components are highly volatile. Therefore, these drawbacks may be overcome by its encapsulation in biodegradable PLGA nanoparticles (THO-NPs) that had been functionalized using several strategies. Moreover, cell viability was studied in HaCat cells, confirming their safety. In order to assess therapeutic efficacy against acne, bacterial reduction capacity and antioxidant properties were assessed. Moreover, the anti-inflammatory and wound-healing abilities of THO-NPs were also confirmed. Additionally, ex vivo antioxidant assessment was carried out using pig skin, demonstrating the suitable antioxidant properties of THO-NPs. Moreover, THO and THO-NPs were dispersed in a gelling system, and stability, rheological properties, and extensibility were assessed. Finally, the biomechanical properties of THO-hydrogel and THO-NP-hydrogel were studied in human volunteers, confirming the suitable activity for the treatment of acne. As a conclusion, THO has been encapsulated into PLGA NPs, and in vitro, ex vivo, and in vivo assessments had been carried out, demonstrating excellent properties for the treatment of inflammatory skin disorders.
Language	English
Publishing date	2024-02-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2813982-3
ISSN	2310-2861 ; 2310-2861
ISSN (online)	2310-2861
ISSN	2310-2861
DOI	10.3390/gels10020149
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Article ; Online: Gel-Dispersed Nanostructured Lipid Carriers Loading Thymol Designed for Dermal Pathologies.

Folle, Camila / Marqués, Ana M / Díaz-Garrido, Natalia / Carvajal-Vidal, Paulina / Sánchez López, Elena / Suñer-Carbó, Joaquim / Halbaut, Lyda / Mallandrich, Mireia / Espina, Marta / Badia, Josefa / Baldoma, Laura / García, Maria Luisa / Calpena, Ana Cristina

International journal of nanomedicine

2024 Volume 19, Page(s) 1225–1248

Abstract: Purpose: Acne vulgaris: Methods: To address this issue, nanostructured lipid carriers (NLC) capable of encapsulating thymol, a natural compound used for the treatment of acne vulgaris, were developed either using ultrasonication probe or high- ... ...

Abstract	Purpose: Acne vulgaris Methods: To address this issue, nanostructured lipid carriers (NLC) capable of encapsulating thymol, a natural compound used for the treatment of acne vulgaris, were developed either using ultrasonication probe or high-pressure homogenization and optimized using 2 Results: NLC encapsulating thymol were developed and optimized and demonstrated a prolonged thymol release. The formulation was dispersed in gels and a screening of several gels was carried out by studying their rheological properties and their skin retention abilities. From them, carbomer demonstrated the capacity to be highly retained in skin tissues, specifically in the epidermis and dermis layers. Moreover, antimicrobial assays against healthy and pathological skin pathogens demonstrated the therapeutic efficacy of thymol-loaded NLC gelling systems since NLC are more efficient in slowly reducing Conclusion: Thymol was successfully loaded into NLC and dispersed in gelling systems, demonstrating that it is a suitable candidate for topical administration against acne vulgaris by eradicating pathogenic bacteria while preserving the healthy skin microbiome.
MeSH term(s)	Humans ; Thymol/pharmacology ; Drug Carriers/chemistry ; Lipids/chemistry ; Nanostructures/chemistry ; Acne Vulgaris ; Anti-Infective Agents/pharmacology ; Gels/chemistry ; Particle Size
Chemical Substances	Thymol (3J50XA376E) ; Drug Carriers ; Lipids ; Anti-Infective Agents ; Gels
Language	English
Publishing date	2024-02-07
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2364941-0
ISSN	1178-2013 ; 1176-9114
ISSN (online)	1178-2013
ISSN	1176-9114
DOI	10.2147/IJN.S433686
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Article ; Online: Gel Formulations with an Echinocandin for Cutaneous Candidiasis: The Influence of Azone and Transcutol on Biopharmaceutical Features.

Pérez-González, Noelia / Espinoza, Lupe Carolina / Rincón, María / Sosa, Lilian / Mallandrich, Mireia / Suñer-Carbó, Joaquim / Bozal-de Febrer, Nuria / Calpena, Ana Cristina / Clares-Naveros, Beatriz

Gels (Basel, Switzerland)

2023 Volume 9, Issue 4

Abstract: Caspofungin is a drug that is used for fungal infections that are difficult to treat, including invasive aspergillosis and candidemia, as well as other forms of invasive candidiasis. The aim of this study was to incorporate Azone in a caspofungin gel ( ... ...

Abstract	Caspofungin is a drug that is used for fungal infections that are difficult to treat, including invasive aspergillosis and candidemia, as well as other forms of invasive candidiasis. The aim of this study was to incorporate Azone in a caspofungin gel (CPF-AZ-gel) and compare it with a promoter-free caspofungin gel (CPF-gel). An in vitro release study using a polytetrafluoroethylene membrane and ex vivo permeation into human skin was adopted. The tolerability properties were confirmed by histological analysis, and an evaluation of the biomechanical properties of the skin was undertaken. Antimicrobial efficacy was determined against
Language	English
Publishing date	2023-04-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2813982-3
ISSN	2310-2861 ; 2310-2861
ISSN (online)	2310-2861
ISSN	2310-2861
DOI	10.3390/gels9040308
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Article ; Online: Alginate Hydrogel Formulation with Ketorolac for the Treatment of Pain Related Sialolithiasis.

Silva, Cristina / Ramos-Yacasi, Gladys / Mallandrich, Mireia / Colom-Codina, Helena / Suñer-Carbó, Joaquim / Pérez-González, Noelia / Calpena, Ana Cristina / Fernández-Campos, Francisco

Gels (Basel, Switzerland)

2023 Volume 9, Issue 5

Abstract: Sialolithiasis mainly affects the oral salivary glands due to the presence of small stones that obstruct the secretion of saliva. The treatment and control of pain and inflammation during the course of this pathology is essential to guarantee the patient' ...

Abstract	Sialolithiasis mainly affects the oral salivary glands due to the presence of small stones that obstruct the secretion of saliva. The treatment and control of pain and inflammation during the course of this pathology is essential to guarantee the patient's comfort. For this reason, a ketorolac calcium cross-linked alginate hydrogel was developed, and it was then applied in the area of the buccal cavity. The formulation was characterized (swelling and degradation profile, extrusion, extensibility, surface morphology, viscosity, and drug release). The drug release was studied ex vivo in static Franz cells and with a dynamic ex vivo method under artificial saliva continuous flow. The product exhibits adequate physicochemical properties considering the intended purpose, and the drug concentrations retained in the mucosa were high enough to deliver a therapeutic local concentration able to reduce the pain associated with the patient's conditions. The results confirmed the suitability of the formulation for application in the mouth.
Language	English
Publishing date	2023-05-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2813982-3
ISSN	2310-2861 ; 2310-2861
ISSN (online)	2310-2861
ISSN	2310-2861
DOI	10.3390/gels9050415
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Article ; Online: Colloidal hydrogel systems of thymol-loaded PLGA nanoparticles designed for acne treatment.

Folle, Camila / Marqués, Ana M / Mallandrich, Mireia / Suñer-Carbó, Joaquim / Halbaut, Lyda / Sánchez-López, Elena / López-Machado, Ana Laura / Díaz-Garrido, Natalia / Badia, Josefa / Baldoma, Laura / Espina, Marta / García, María Luisa / Calpena, Ana Cristina

Colloids and surfaces. B, Biointerfaces

2023 Volume 234, Page(s) 113678

Abstract: Thymol-loaded PLGA nanoparticles (TH-NPs) were incorporated into different semi-solid formulations using variable gelling agents (carbomer, polysaccharide and poloxamer). The formulations were physicochemically characterized in terms of size, ... ...

Abstract	Thymol-loaded PLGA nanoparticles (TH-NPs) were incorporated into different semi-solid formulations using variable gelling agents (carbomer, polysaccharide and poloxamer). The formulations were physicochemically characterized in terms of size, polydispersity index and zeta potential. Moreover, stability studies were performed by analyzing the backscattering profile showing that the gels were able to increase the nanoparticles stability at 4 °C. Moreover, rheological properties showed that all gels were able to increase the viscosity of TH-NPs with the carbomer gels showing the highest values. Moreover, the observation of carbomer dispersed TH-NPs under electron microscopical techniques showed 3D nanometric cross-linked filaments with the NPs found embedded in the threads. In addition, cytotoxicity studies showed that keratinocyte cells in contact with the formulations obtained cell viability values higher than 70 %. Furthermore, antimicrobial efficacy was assessed against C. acnes and S. epidermidis showing that the formulations eliminated the pathogenic C. acnes but preserved the resident S. epidermidis which contributes towards a healthy skin microbiota. Finally, biomechanical properties of TH-NPs dispersed in carbomer gels in contact with healthy human skin were studied showing that they did not alter skin properties and were able to reduce sebum which is increased in acne vulgaris. As a conclusion, TH-NPs dispersed in semi-solid formulations and, especially in carbomer gels, may constitute a suitable solution for the treatment of acne vulgaris.
MeSH term(s)	Humans ; Hydrogels/chemistry ; Thymol/pharmacology ; Skin ; Acne Vulgaris/drug therapy ; Polylactic Acid-Polyglycolic Acid Copolymer ; Nanoparticles/chemistry
Chemical Substances	Hydrogels ; Thymol (3J50XA376E) ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS)
Language	English
Publishing date	2023-12-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2023.113678
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Article ; Online: Semi-solid functionalized nanostructured lipid carriers loading thymol for skin disorders.

Folle, Camila / Sánchez-López, Elena / Mallandrich, Mireia / Díaz-Garrido, Natalia / Suñer-Carbó, Joaquim / Halbaut, Lyda / Carvajal-Vidal, Paulina / Marqués, Ana M / Espina, Marta / Badia, Josefa / Baldoma, Laura / García, Maria Luisa / Calpena, Ana Cristina

International journal of pharmaceutics

2023 Volume 651, Page(s) 123732

Abstract: Acne constitutes one of the most prevalent skin disorder affecting both skin and mental health of patients. However, no cure has been developed so far. In this area, Thymol constitutes a potential candidate since it is able to restore the healthy ... ...

Abstract	Acne constitutes one of the most prevalent skin disorder affecting both skin and mental health of patients. However, no cure has been developed so far. In this area, Thymol constitutes a potential candidate since it is able to restore the healthy microbiota of the skin. However, its permeation properties cause its fast elimination and, to avoid this problem, thymol has been loaded into nanostructured lipid carriers (TH-NLCs). Moreover, to increase the suitability of these systems for skin applications, several surface functionalization strategies of TH-NLCs had been assessed. Among the different molecules, phosphatidylcholine-TH-NLCs demonstrated to be safe as well as to provide high antioxidant activity in cellular studies. Therefore, to administer these systems to the skin, functionalized TH-NLCs were dispersed into a carbomer gel developing semi-solid formulations. Rheological properties, porosity and extensibility of TH dispersed in carbomer as well as phosphatidylcholine-TH-NLCs were assessed demonstrating suitable properties for dermal applications. Moreover, both formulations were applied in healthy volunteers demonstrating that gel-phosphatidylcholine-TH-NLCs were able to increase in skin hydration, decrease water loss and reduce skin sebum. Therefore, gel-phosphatidylcholine-TH-NLCs proved to be a suitable system for skin pathologies linked with high sebum generation, loss of hydration and high oxidation, such as acne vulgaris.
MeSH term(s)	Humans ; Thymol ; Nanoparticles ; Drug Carriers/therapeutic use ; Skin ; Nanostructures ; Acne Vulgaris/drug therapy ; Phosphatidylcholines ; Particle Size
Chemical Substances	Thymol (3J50XA376E) ; Drug Carriers ; Phosphatidylcholines
Language	English
Publishing date	2023-12-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2023.123732
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Article: Effects of Metamitron under Different Relative Humidity Conditions on the Fruit Abscission of Malus domestica Borkh. Cultivars

Rosa, Nídia / Verjans, Wim / Àvila, Glória / Carbó, Joaquim / Bonany, Joan / Ramalho, José Cochicho / Asín, Luís / Oliveira, Cristina Moniz

Horticulturae. 2020 Nov. 23, v. 6, no. 4

2020

Abstract: Metamitron is an apple (Malus domestica Borkh.) fruit thinner that acts by reducing the photosynthetic capacity of trees. Relative humidity may influence thinning efficacy; however, the broadness of this effect is not yet fully understood. Trials were ... ...

Abstract	Metamitron is an apple (Malus domestica Borkh.) fruit thinner that acts by reducing the photosynthetic capacity of trees. Relative humidity may influence thinning efficacy; however, the broadness of this effect is not yet fully understood. Trials were set in Sint-Truiden (Belgium) in 2018 and Lleida and Girona (Spain) in 2019, using 4-year-old cvs. Braeburn and Elstar trees in Belgium, and 16-year-old cv. Golden Reinders trees in Spain. Four treatments were implemented at the stage of 12–14 mm fruit diameter: (a) CTR—control, trees under natural environmental conditions; (b) HH—high humidity, trees submitted to artificially increased air relative humidity applied for 3 h prior to the beginning of the experiment; (c) MET—trees sprayed with 247.5 mg/L metamitron; (d) MET + HH—trees submitted to the combination of increased humidity (HH) and metamitron (MET) application. In Belgium, metamitron absorption by leaves was greater than in Spain. This might be related to morphological characteristics of the leaves which developed under greater natural relative humidity levels in Belgium than in Spain. Compared to MET alone, ‘Braeburn’ and ‘Elstar’ demonstrated significantly greater metamitron absorption, 59% and 84%, respectively, under MET + HH, accompanied by declines in leaf net photosynthesis (10% and 32%, respectively) and sucrose (31% and 26%, respectively). At harvest, MET + HH treatment reduced yield by 24% and 32% in ‘Braeburn’ and ‘Elstar’, respectively, when compared with MET alone. A large reduction (considered over thinning) in the yield of ‘Elstar’ occurred. In contrast, metamitron absorption by ‘Golden Reinders’ using MET alone was similar to MET + HH; however, there was a slight foliar sugar reduction in the latter treatment. In addition, both treatments enhanced shoot growth and increased fruit abscission with similar improvements in fruit weight and size. In this study, high relative humidity enhanced fruit thinning efficacy under certain circumstances, such as age or genetic predisposal, which left the tree more susceptible to a negative carbohydrate balance. For instance, ‘Braeburn’ and ‘Elstar’ were easier to thin when compared to ‘Golden Reinders’. In addition, this study raises a question that requires further research regarding the impact of HH before and after spraying as well as its effect in combination with higher temperatures.
Keywords	Malus domestica ; absorption ; age ; apples ; cultivars ; diameter ; environmental factors ; fruit drop ; fruit weight ; fruits ; leaves ; metamitron ; photosynthesis ; relative humidity ; research ; spraying ; sucrose ; temperature ; trees ; Belgium ; Spain
Language	English
Dates of publication	2020-1123
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2813983-5
ISSN	2311-7524
ISSN	2311-7524
DOI	10.3390/horticulturae6040089
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Evaluation of chemical fruit thinning efficiency using Brevis® (Metamitron) on apple trees (‘Gala’) under Spanish conditions

González, Luis / Torres, Estanis / Avila, Gloria / Bonany, Joan / Alegre, Simó / Carbó, Joaquim / Martín, Begoña / Recasens, Inmaculada / Asín, Luis

Scientia horticulturae 2020 Feb. 5, v. 261, p. 109003

2020 , Page(s) 109003

Abstract: Thinning is an important technique in apple growing which is used to reduce the number of fruits per plant and achieve commercial fruit size and quality. The objective of this work was to evaluate the efficacy of one and two applications of the chemical ... ...

Abstract	Thinning is an important technique in apple growing which is used to reduce the number of fruits per plant and achieve commercial fruit size and quality. The objective of this work was to evaluate the efficacy of one and two applications of the chemical thinner Brevis® in Gala apple applied at different fruit sizes and at different intervals between the first and second spray. The trials were conducted over two seasons from 2015 to 2016 in apple orchards of the IRTA experimental agricultural stations of Mas Badia and Lleida (Spain). One or two applications with Brevis® were applied at different fruit sizes (king fruit diameter ranging between 7.5 and 13.5 mm) and at a rate of 1.65 kg/ha for all treatments. Under the trial conditions, a Brevis® thinning effect was observed in all trials with a reduction in crop load, fruit set and number of fruits per tree which varied according to the number of applications. In addition, average fruit weight, color and diameter increased significantly with treatments in which Brevis® reduced the number of fruits per tree. The degree of abscission of Brevis® was highly dependent on night temperature and, for this reason, there was a high degree of variability between trials in terms of efficacy. Our results show that the number of days between applications was not as important a factor for Brevis® efficacy as the difference in night temperature in the days immediately after its application.
Keywords	Night temperature ; Metamitron ; Fruit abscission ; Carbohydrate deficit ; Crop load
Language	English
Dates of publication	2020-0205
Size	p. 109003
Publishing place	International Society for Horticultural Science.
Document type	Article ; Online
ZDB-ID	185557-8
ISSN	0304-4238
ISSN	0304-4238
DOI	10.1016/j.scienta.2019.109003
Database	NAL-Catalogue (AGRICOLA)

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Article: Screening of eco-friendly thinning agents and adjusting mechanical thinning on ‘Gala’, ‘Golden Delicious’ and ‘Fuji’ apple trees

Lordan, Jaume / Alins, Georgina / Àvila, Glòria / Torres, Estanis / Carbó, Joaquim / Bonany, Joan / Alegre, Simó

Scientia horticulturae. 2018 Sept. 15, v. 239

2018

Abstract: Fruit thinning is the most important yet difficult practice that drives orchard profitability. High labor costs and difficulty to improve return bloom by hand thinning have left chemical thinning as the main method used by growers. However, ... ...

Abstract	Fruit thinning is the most important yet difficult practice that drives orchard profitability. High labor costs and difficulty to improve return bloom by hand thinning have left chemical thinning as the main method used by growers. However, unpredictability and safety/environment concerns regarding chemical thinning have set mechanical thinning as a sound alternative. Thirteen field experiments were performed during 2004–2016 in order to evaluate several agents for their use as new thinners, and adjust mechanical thinning on ‘Gala’, ‘Golden Delicious’ and ‘Fuji’. Olive oil applied at bloom reduced crop load, but russetting was also increased. Therefore, while their use is not advisable for russetting prone cultivars such as ‘Golden Delicious’, it could be a good thinner for cultivars like ‘Red Delicious’. Lime sulfur did not have a consistent thinning effect in our study when applied at bloom. Overall, no differences regarding economic value between hand, chemical, and mechanical blossom thinning were observed, suggesting mechanical thinning as a valid alternative approach. For ‘Gala’ strains, 6 km h−1 and 250 rpm with 270 strings was the best configuration to provide an ideal crop load of ∼6 fruit/cm2 of TCSA and an average fruit size of 170 g. For ‘Fuji’, 5 km h−1 and 320 rpm with 270 strings provided a crop load in accordance to the optimum range for this cultivar in our conditions. However, combination of mechanical thinning plus chemical treatments might be the ideal strategy for ‘Fuji’ strains when the initial number of flower clusters per tree is above 500. For ‘Golden Delicious’ strains, 6 km h−1 and 230 rpm with 270 strings was the best configuration to provide an ideal crop load within the optimum range. Mechanical thinning timing was also examined at different phenological stages (E2, F1, F2, and G), with no significant differences regarding yield, fruit size or crop load between them. Two prediction models (‘Gala’ & ‘Golden Delicious’) were developed to adjust the right tractor and rotational speeds depending on the initial number of flower clusters. The method begins with first calculating the final fruit number needed per tree (crop load for each particular cultivar) in order to achieve the desired yield. Then, tractor and rotational speeds can be determined by the model once knowing the initial number of flower clusters per tree.
Keywords	apples ; chemical treatment ; cultivars ; deblossoming ; economic valuation ; field experimentation ; flowers ; fruits ; growers ; hand thinning ; models ; olive oil ; orchards ; phenology ; profitability ; screening ; sulfur ; tractors ; trees ; wages and remuneration
Language	English
Dates of publication	2018-0915
Size	p. 141-155.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	185557-8
ISSN	0304-4238
ISSN	0304-4238
DOI	10.1016/j.scienta.2018.05.027
Database	NAL-Catalogue (AGRICOLA)

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