Amélia Silva - Profile on Academia.edu (original) (raw)
Papers by Amélia Silva
Materials, Dec 8, 2021
The eye is a very complex organ comprising several physiological and physical barriers that compr... more The eye is a very complex organ comprising several physiological and physical barriers that compromise drug absorption into deeper layers. Nanoemulsions are promising delivery systems to be used in ocular drug delivery due to their innumerous advantages, such as high retention time onto the site of application and the modified release profile of loaded drugs, thereby contributing to increasing the bioavailability of drugs for the treatment of eye diseases, in particular those affecting the posterior segment. In this review, we address the main factors that govern the development of a suitable nanoemulsion formulation for eye administration to increase the patient's compliance to the treatment. Appropriate lipid composition and type of surfactants (with a special emphasis on cationic compounds) are discussed, together with manufacturing techniques and characterization methods that are instrumental for the development of appropriate ophthalmic nanoemulsions.
Antioxidants, Dec 31, 2019
Thymus mastichina, also called mastic thyme or Spanish marjoram, is endemic to the Iberian Penins... more Thymus mastichina, also called mastic thyme or Spanish marjoram, is endemic to the Iberian Peninsula, where it is widely used in folk medicine especially for treating digestive and respiratory systems disorders, and as a condiment to season olives. This work describes for the first time the detailed phenolic composition of exhaustive hydroethanolic extracts and aqueous decoctions of Thymus mastichina. Unlike other species of the Thymus genera, Thymus mastichina extracts contain high amounts of salvianolic acid derivatives, with salvianolic acid A isomer being the main derivative. This isomer was identified in extracts from Thymus mastichina for the first time. Also, an undescribed salvianolic acid derivative in Thymus mastichina was identified and its structure was tentatively described. Extracts from Thymus mastichina showed significant scavenging activity of 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation, hydroxyl, and nitric oxide radicals. The anti-proliferative effect of both T. mastichina extracts were tested against Caco-2 and HepG2 cells; the hydroethanolic extract showed a high anti-proliferative activity against Caco-2 cells compared to HepG2 cells (at 24 h exposure, the concentration that inhibits 50% of proliferation, IC 50 , was 71.18 ± 1.05 µg/mL and 264.60 ± 11.78 µg/mL for Caco-2 and HepG2, respectively). Thus, these results make this species a promising candidate for further investigation of its anti-tumoral potential. Therefore, Thymus mastichina can be potentially used as a functional food (used as a decoction or herbal tea) or as a source of bioactive ingredients with antioxidant and anti-proliferative properties.
Food Chemistry, Nov 1, 2020
The polyphenol compositions of Thymus × citriodorus and Thymus vulgaris extracts as obtained by e... more The polyphenol compositions of Thymus × citriodorus and Thymus vulgaris extracts as obtained by exhaustive hydroethanolic (HE) extraction and aqueous decoction (AD) were compared. In addition, their compositions and bioactivities were compared to those of Thymus pulegioides and Thymus mastichina, grown under the same edaphoclimatic conditions, and Thymus carnosus. Rosmarinic acid was the most abundant polyphenol followed by luteolin-hexuronide, salvianolic acids I and K. Cluster analysis suggests a similarity of the polyphenol composition of T. citriodorus and T. vulgaris. A significant antioxidant activity was observed and correlated with their polyphenol levels. The same being observed for the higher anti-proliferative activity/cytotoxicity of HE extracts on Caco-2 and HepG2 cells as compared to AD extracts. Significant association between the total phenolic compounds with the anti-proliferative activity, for both cell lines, was observed. These results support the importance of salvianolic acids levels in Thymus extracts and their in vitro anti-proliferative/cytotoxic activities.
Antioxidants, Mar 8, 2023
Thymus carnosus Boiss. is a near-threatened species, and, as for many species, its potential for ... more Thymus carnosus Boiss. is a near-threatened species, and, as for many species, its potential for medicinal purposes may be lost if measures towards plant protection are not taken. A way of preserving these species is to increase knowledge about their medicinal properties and economic potential. Thus, with the objective of studying the potentiality of introducing T. carnosus as a crop, the stability of the phytochemical profile of T. carnosus was studied during a period of three years by comparing the phytochemical profile of extracts obtained from plants harvested in two different edaphoclimatic locations, as well as by comparing the respective bioactivities, namely, antioxidant, antidiabetic, antiaging, and neuroprotective activities. It was reported, for the first time, the effect of annual variation and geographic location in the phytochemical composition of aqueous decoction and hydroethanolic extracts of T. carnosus. In addition, the presence of two salvianolic acid B/E isomers in T. carnosus extracts is here described for the first time. Despite the variations in phytochemical composition, according to harvesting location or year, T. carnosus extracts maintain high antioxidant activity, assessed by their capacity to scavenge ABTS •-radicals, as well as to prevent β-carotene bleaching. All extracts presented significant potential to inhibit acetylcholinesterase (AChE), tyrosinase, and α-glucosidase, denoting neuroprotective, anti-aging, and anti-diabetic potential. In conclusion, the vegetative stage and location of harvest are key factors to obtain the maximum potential of this species, namely, a phytochemical profile with health benefit bioactivities.
International Journal of Molecular Sciences
Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is kn... more Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the nonexudative (dry form) and the exudative (wet form). Currently, there is no ideal treatment available for AMD. Recommended standard treatments are based on the use of vascular endothelial growth factor (VEGF), with the disadvantage of requiring repeated intravitreal injections which hinder patient’s compliance to the therapy. In recent years, several synthetic and natural active compounds have been proposed as innovative therapeutic strategies against this disease. There is a growing interest in the development of formulations based on nanotechnology because of its important role in the management of posterior eye segment disorders, without the use of intravitreal injections, and furthermore, with the potential to prolong drug release and thus reduce adverse...
International Journal of Molecular Sciences
The complexity of the eye structure and its physiology turned ocular drug administration into one... more The complexity of the eye structure and its physiology turned ocular drug administration into one of the most challenging topics in the pharmaceutical field. Ocular inflammation is one of the most common ophthalmic disorders. Topical administration of anti-inflammatory drugs is also commonly used as a side treatment in tissue repair and regeneration. The difficulty in overcoming the eye barriers, which are both physical and chemical, reduces drug bioavailability, and the frequency of administration must be increased to reach the therapeutic effect. However, this can cause serious side effects. Lipid nanoparticles seem to be a great alternative to ocular drug delivery as they are composed from natural excipients and can encapsulate both hydrophilic and lipophilic drugs of different sources, and their unique properties, as their excellent biocompatibility, safety and adhesion allow to increase the bioavailability, compliance and achieve a sustained drug release. They are also very sta...
Bioengineering
Microemulsions and nanoemulsions are lipid-based pharmaceutical systems with a high potential to ... more Microemulsions and nanoemulsions are lipid-based pharmaceutical systems with a high potential to increase the permeation of drugs through the skin. Although being isotropic dispersions of two nonmiscible liquids (oil and water), significant differences are encountered between microemulsions and nanoemulsions. Microemulsions are thermodynamically stable o/w emulsions of mean droplet size approximately 100–400 nm, whereas nanoemulsions are thermodynamically unstable o/w emulsions of mean droplet size approximately 1 to 100 nm. Their inner oil phase allows the solubilization of lipophilic drugs, achieving high encapsulation rates, which are instrumental for drug delivery. In this review, the importance of these systems, the key differences regarding their composition and production processes are discussed. While most of the micro/nanoemulsions on the market are held by the cosmetic industry to enhance the activity of drugs used in skincare products, the development of novel pharmaceuti...
Heliyon, 2022
The skin is a complex and multifunctional organ, in which the static versus dynamic balance is re... more The skin is a complex and multifunctional organ, in which the static versus dynamic balance is responsible for its constant adaptation to variations in the external environment that is continuously exposed. One of the most important functions of the skin is its ability to act as a protective barrier, against the entry of foreign substances and against the excessive loss of endogenous material. Human skin imposes physical, chemical and biological limitations on all types of permeating agents that can cross the epithelial barrier. For a molecule to be passively permeated through the skin, it must have properties, such as dimensions, molecular weight, pKa and hydrophiliclipophilic gradient, appropriate to the anatomy and physiology of the skin. These requirements have limited the number of commercially available products for dermal and transdermal administration of drugs. To understand the mechanisms involved in the drug permeation process through the skin, the approach should be multidisciplinary in order to overcome biological and pharmacotechnical barriers. The study of the mechanisms involved in the permeation process, and the ways to control it, can make this route of drug administration cease to be a constant promise and become a reality. In this work, we address the physicochemical and biopharmaceutical aspects encountered in the pathway of drugs through the skin, and the potential added value of using solid lipid nanoparticles (SLN) and nanostructured lipid vectors (NLC) to drug permeation/penetration through this route. The technology and architecture for obtaining lipid nanoparticles are described in detail, namely the composition, production methods and the ability to release pharmacologically active substances, as well as the application of these systems in the vectorization of various pharmacologically active substances for dermal and transdermal applications. The characteristics of these systems in terms of dermal application are addressed, such as biocompatibility, occlusion, hydration, emollience and the penetration of pharmacologically active substances. The advantages of using these systems over conventional formulations are described and explored from a pharmaceutical point of view. This article is a part of the Lipid-Based Nanoparticles Special issue.
Bioengineering, 2021
Surfactants are amphiphilic compounds having hydrophilic and hydrophobic moieties in their struct... more Surfactants are amphiphilic compounds having hydrophilic and hydrophobic moieties in their structure. They can be of synthetic or of microbial origin, obtained respectively from chemical synthesis or from microorganisms’ activity. A new generation of ecofriendly surfactant molecules or biobased surfactants is increasingly growing, attributed to their versatility of applications. Surfactants can be used as drug delivery systems for a range of molecules given their capacity to create micelles which can promote the encapsulation of bioactives of pharmaceutical interest; besides, these assemblies can also show antimicrobial properties. The advantages of biosurfactants include their high biodegradability profile, low risk of toxicity, production from renewable sources, functionality under extreme pH and temperature conditions, and long-term physicochemical stability. The application potential of these types of polymers is related to their properties enabling them to be processed by emuls...
Materials, 2021
Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for sever... more Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these “virus-sized particles” can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells’ interactions. In this review, the Comet assay is described, discussing several examples of its applicatio...
Rendiconti Lincei. Scienze Fisiche e Naturali, 2021
Medicinal plants always are part of folk medicine and are nowadays receiving worldwide attention ... more Medicinal plants always are part of folk medicine and are nowadays receiving worldwide attention for prophylaxis, management, and treatment of several diseases, as an alternative to chemical drugs. The current work provided a comprehensive overview and analysis of the Astragalus and health relationship in literature. The analysis of their therapeutic potential is thus instrumental to understand their bioactivity. Among these, the flowering medicinal plant Astragalus membranaceus has raised interest due to several beneficial health effects. This perspective review discussed the botanical, geographical, historical, and the therapeutic properties of A. membranaceus, with a special focus on its health improving effects and medicinal applications both in vitro and in vivo. Graphic abstract
Nanomaterials, 2021
Oil-in-water nanoemulsions (NEs) are considered a suitable nanotechnological approach to improve ... more Oil-in-water nanoemulsions (NEs) are considered a suitable nanotechnological approach to improve the eye-related bioavailability of lipophilic drugs. The potential of cationic NEs is prominent due to the electrostatic interaction that occurs between the positively charged droplets with the negatively charged mucins present in the tear film. This interaction offers prolonged NEs residence at the ocular surface, increasing the drug absorption. Triamcinolone acetonide (TA) is one of the first pharmacologic strategies applied as an intravitreal injection in the treatment of age-related macular degeneration (AMD). Newly synthesized quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and quinuclidine surfactants have been screened with the purpose to select the best compound to formulate long-term stable NEs that combine the best physicochemical properties for the loading of TA intended for ocular administration.
Molecules, 2020
Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be lo... more Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules and nanospheres, which are distinguished by the morphological structure. Polymeric NPs have shown great potential for targeted delivery of drugs for the treatment of several diseases. In this review, we discuss the most commonly used methods for the production and characterization of polymeric NPs, the association efficiency of the active compound to the polymeric core, and the in vitro release mechanisms. As the safety of nanoparticles is a high priority, we also discuss the toxicology and ecotoxicology of nanoparticles to humans and to the environment.
Heliyon, 2020
Sunscreens have been employed on daily skin care for centuries. Their role in protecting the skin... more Sunscreens have been employed on daily skin care for centuries. Their role in protecting the skin from sun damage, avoiding accelerated photoaging and even limiting the risk of development of skin cancer is unquestionable. Although several chemical and physical filters are approved as sunscreens for human use, their safety profile is dependent on their concentration in the formulation which governs their acceptance by the regulatory agencies. A strategic delivery of such molecules should provide a UV protection and limit the skin penetration. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) may offer an alternative approach to achieve a synergistic effect on the UV protection when loaded with sunscreens as particles themselves also have a UV light scattering effect. Besides, the lipid character of SLN and NLC improves the encapsulation of lipophilic compounds, with enhanced loading capacity. Silica nanoparticles have also been employed in sunscreen formulations. Due to the formed sol-gel complexes, which covalently entrap sunscreen molecules, a controlled release is also achieved. In the present work, we have developed a new sunscreen formulation composed of hybrid SLN-Silica particles loaded with octyl methoxycinnamate (Parsol ® MCX), and their further incorporation into a hydrogel for skin administration. Hybrid SLN-silica particles of 210.0 AE 3.341 nm of mean size, polydispersity below 0.3, zeta potential of ca. |7| mV, loading capacity of 19.9% and encapsulation efficiency of 98.3% have been produced. Despite the slight negative surface charge, the developed hybrid nanoparticles remained physicochemically stable over the study period. Turbiscan transmission profiles confirmed the colloidal stability of the formulations under stress conditions. The texture profile analysis of Parsol-SLN and Parsol-SLN-Si revealed semisolid properties (e.g. adhesiveness, hardness, cohesiveness, springiness, gumminess, chewiness, resilience) suitable for topical application, together with the bioadhesiveness in the skin of pig ears. The non-irritation profile of the hybrid nanoparticles before and after dispersion into Carbopol hydrogels was confirmed by HET-CAM test.
Forests, 2020
Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cos... more Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cost-effective production when compared to chemical drugs, encouraging researchers to further exploit the therapeutic potential of the former. One of the most popular medicinal plants is Vitex agnus-castus L., grown in tropical and sub-tropical regions, to which different health benefits have already been attributed. In this perspective article, the in vitro and in vivo therapeutic properties of V. agnus-castus L. have been analyzed and reviewed with a special focus on its health-promoting effects and potential nutraceutical applications.
Molecules, 2020
Carnitine can be considered a conditionally essential nutrient for its importance in human physio... more Carnitine can be considered a conditionally essential nutrient for its importance in human physiology. This paper provides an updated picture of the main features of carnitine outlining its interest and possible use. Particular attention has been addressed to its beneficial properties, exploiting carnitine’s properties and possible use by considering the main in vitro, in animal, and human studies. Moreover, the main aspects of carnitine-based dietary supplements have been indicated and defined with reference to their possible beneficial health properties.
Materials, 2020
Photodynamic therapy is an innovative treatment approach broadly directed towards oncological dis... more Photodynamic therapy is an innovative treatment approach broadly directed towards oncological diseases. Its applicability and efficiency are closely related to the interaction of three main components, namely a photosensitizer, light and molecular triplet oxygen, which should drive cell death. Recently, several studies have demonstrated that squaraine cyanine dyes have a set of photophysical and photochemical properties that have made of these compounds’ potential photosensitizers for this therapeutic modality. In the present research work, we describe the synthesis and characterization of four quinoline- and benzoselenazole-derived unsymmetrical squaraine cyanine dyes. Except for the precursor of aminosquaraine dyes, i.e., O-methylated derivative, all dyes were evaluated for their behavior and absorption capacity in different organic and aqueous solvents, their ability to form singlet oxygen, their light-stability, and in vitro phototherapeutic effects against two human breast canc...
Applied Sciences, 2020
Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chr... more Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes. Studies in animal models and patients with diabetes have shown a high expression of the inflammatory molecules that are involved in the progression of diabetic retinopathy. Uveal melanoma is an eye tumour that remains highly deadly, because despite the correct treatment, it still causes metastasis in about 50% of patients. This type of tumour has the ability to produce and store melanin, which may result in resistance to therapy. Over time there has been development of new therapies for this disease, such as radiotherapy and surgical resection. In this review, we discuss diabetic retinopathy and ocular melanoma, their relationship with angiogenesis and the current anti-angiogenic therapies for their treatment.
Nanomaterials, 2020
Metal-based nanoparticles have been extensively investigated for a set of biomedical applications... more Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while...
Pathogens, 2019
The incidence of neglected diseases in tropical countries, such as Leishmaniasis and Chagas’s dis... more The incidence of neglected diseases in tropical countries, such as Leishmaniasis and Chagas’s disease, is attributed to a set of biological and ecological factors associated with the socioeconomic context of developing countries and with a significant burden to health care systems. Both Leishmaniasis and Chagas’s disease are caused by different protozoa and develop diverse symptoms, which depend on the specific species infecting man. Currently available drugs to treat these disorders have limited therapeutic outcomes, frequently due to microorganisms’ drug resistance. In recent years, significant efforts have been made towards the development of innovative drug delivery systems aiming to improve bioavailability and pharmacokinetic profiles of classical drug therapy. This paper discusses the key facts of Leishmaniasis and Chagas’s disease, the currently available pharmacological therapies and the new drug delivery systems for conventional drugs.
Materials, Dec 8, 2021
The eye is a very complex organ comprising several physiological and physical barriers that compr... more The eye is a very complex organ comprising several physiological and physical barriers that compromise drug absorption into deeper layers. Nanoemulsions are promising delivery systems to be used in ocular drug delivery due to their innumerous advantages, such as high retention time onto the site of application and the modified release profile of loaded drugs, thereby contributing to increasing the bioavailability of drugs for the treatment of eye diseases, in particular those affecting the posterior segment. In this review, we address the main factors that govern the development of a suitable nanoemulsion formulation for eye administration to increase the patient's compliance to the treatment. Appropriate lipid composition and type of surfactants (with a special emphasis on cationic compounds) are discussed, together with manufacturing techniques and characterization methods that are instrumental for the development of appropriate ophthalmic nanoemulsions.
Antioxidants, Dec 31, 2019
Thymus mastichina, also called mastic thyme or Spanish marjoram, is endemic to the Iberian Penins... more Thymus mastichina, also called mastic thyme or Spanish marjoram, is endemic to the Iberian Peninsula, where it is widely used in folk medicine especially for treating digestive and respiratory systems disorders, and as a condiment to season olives. This work describes for the first time the detailed phenolic composition of exhaustive hydroethanolic extracts and aqueous decoctions of Thymus mastichina. Unlike other species of the Thymus genera, Thymus mastichina extracts contain high amounts of salvianolic acid derivatives, with salvianolic acid A isomer being the main derivative. This isomer was identified in extracts from Thymus mastichina for the first time. Also, an undescribed salvianolic acid derivative in Thymus mastichina was identified and its structure was tentatively described. Extracts from Thymus mastichina showed significant scavenging activity of 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation, hydroxyl, and nitric oxide radicals. The anti-proliferative effect of both T. mastichina extracts were tested against Caco-2 and HepG2 cells; the hydroethanolic extract showed a high anti-proliferative activity against Caco-2 cells compared to HepG2 cells (at 24 h exposure, the concentration that inhibits 50% of proliferation, IC 50 , was 71.18 ± 1.05 µg/mL and 264.60 ± 11.78 µg/mL for Caco-2 and HepG2, respectively). Thus, these results make this species a promising candidate for further investigation of its anti-tumoral potential. Therefore, Thymus mastichina can be potentially used as a functional food (used as a decoction or herbal tea) or as a source of bioactive ingredients with antioxidant and anti-proliferative properties.
Food Chemistry, Nov 1, 2020
The polyphenol compositions of Thymus × citriodorus and Thymus vulgaris extracts as obtained by e... more The polyphenol compositions of Thymus × citriodorus and Thymus vulgaris extracts as obtained by exhaustive hydroethanolic (HE) extraction and aqueous decoction (AD) were compared. In addition, their compositions and bioactivities were compared to those of Thymus pulegioides and Thymus mastichina, grown under the same edaphoclimatic conditions, and Thymus carnosus. Rosmarinic acid was the most abundant polyphenol followed by luteolin-hexuronide, salvianolic acids I and K. Cluster analysis suggests a similarity of the polyphenol composition of T. citriodorus and T. vulgaris. A significant antioxidant activity was observed and correlated with their polyphenol levels. The same being observed for the higher anti-proliferative activity/cytotoxicity of HE extracts on Caco-2 and HepG2 cells as compared to AD extracts. Significant association between the total phenolic compounds with the anti-proliferative activity, for both cell lines, was observed. These results support the importance of salvianolic acids levels in Thymus extracts and their in vitro anti-proliferative/cytotoxic activities.
Antioxidants, Mar 8, 2023
Thymus carnosus Boiss. is a near-threatened species, and, as for many species, its potential for ... more Thymus carnosus Boiss. is a near-threatened species, and, as for many species, its potential for medicinal purposes may be lost if measures towards plant protection are not taken. A way of preserving these species is to increase knowledge about their medicinal properties and economic potential. Thus, with the objective of studying the potentiality of introducing T. carnosus as a crop, the stability of the phytochemical profile of T. carnosus was studied during a period of three years by comparing the phytochemical profile of extracts obtained from plants harvested in two different edaphoclimatic locations, as well as by comparing the respective bioactivities, namely, antioxidant, antidiabetic, antiaging, and neuroprotective activities. It was reported, for the first time, the effect of annual variation and geographic location in the phytochemical composition of aqueous decoction and hydroethanolic extracts of T. carnosus. In addition, the presence of two salvianolic acid B/E isomers in T. carnosus extracts is here described for the first time. Despite the variations in phytochemical composition, according to harvesting location or year, T. carnosus extracts maintain high antioxidant activity, assessed by their capacity to scavenge ABTS •-radicals, as well as to prevent β-carotene bleaching. All extracts presented significant potential to inhibit acetylcholinesterase (AChE), tyrosinase, and α-glucosidase, denoting neuroprotective, anti-aging, and anti-diabetic potential. In conclusion, the vegetative stage and location of harvest are key factors to obtain the maximum potential of this species, namely, a phytochemical profile with health benefit bioactivities.
International Journal of Molecular Sciences
Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is kn... more Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the nonexudative (dry form) and the exudative (wet form). Currently, there is no ideal treatment available for AMD. Recommended standard treatments are based on the use of vascular endothelial growth factor (VEGF), with the disadvantage of requiring repeated intravitreal injections which hinder patient’s compliance to the therapy. In recent years, several synthetic and natural active compounds have been proposed as innovative therapeutic strategies against this disease. There is a growing interest in the development of formulations based on nanotechnology because of its important role in the management of posterior eye segment disorders, without the use of intravitreal injections, and furthermore, with the potential to prolong drug release and thus reduce adverse...
International Journal of Molecular Sciences
The complexity of the eye structure and its physiology turned ocular drug administration into one... more The complexity of the eye structure and its physiology turned ocular drug administration into one of the most challenging topics in the pharmaceutical field. Ocular inflammation is one of the most common ophthalmic disorders. Topical administration of anti-inflammatory drugs is also commonly used as a side treatment in tissue repair and regeneration. The difficulty in overcoming the eye barriers, which are both physical and chemical, reduces drug bioavailability, and the frequency of administration must be increased to reach the therapeutic effect. However, this can cause serious side effects. Lipid nanoparticles seem to be a great alternative to ocular drug delivery as they are composed from natural excipients and can encapsulate both hydrophilic and lipophilic drugs of different sources, and their unique properties, as their excellent biocompatibility, safety and adhesion allow to increase the bioavailability, compliance and achieve a sustained drug release. They are also very sta...
Bioengineering
Microemulsions and nanoemulsions are lipid-based pharmaceutical systems with a high potential to ... more Microemulsions and nanoemulsions are lipid-based pharmaceutical systems with a high potential to increase the permeation of drugs through the skin. Although being isotropic dispersions of two nonmiscible liquids (oil and water), significant differences are encountered between microemulsions and nanoemulsions. Microemulsions are thermodynamically stable o/w emulsions of mean droplet size approximately 100–400 nm, whereas nanoemulsions are thermodynamically unstable o/w emulsions of mean droplet size approximately 1 to 100 nm. Their inner oil phase allows the solubilization of lipophilic drugs, achieving high encapsulation rates, which are instrumental for drug delivery. In this review, the importance of these systems, the key differences regarding their composition and production processes are discussed. While most of the micro/nanoemulsions on the market are held by the cosmetic industry to enhance the activity of drugs used in skincare products, the development of novel pharmaceuti...
Heliyon, 2022
The skin is a complex and multifunctional organ, in which the static versus dynamic balance is re... more The skin is a complex and multifunctional organ, in which the static versus dynamic balance is responsible for its constant adaptation to variations in the external environment that is continuously exposed. One of the most important functions of the skin is its ability to act as a protective barrier, against the entry of foreign substances and against the excessive loss of endogenous material. Human skin imposes physical, chemical and biological limitations on all types of permeating agents that can cross the epithelial barrier. For a molecule to be passively permeated through the skin, it must have properties, such as dimensions, molecular weight, pKa and hydrophiliclipophilic gradient, appropriate to the anatomy and physiology of the skin. These requirements have limited the number of commercially available products for dermal and transdermal administration of drugs. To understand the mechanisms involved in the drug permeation process through the skin, the approach should be multidisciplinary in order to overcome biological and pharmacotechnical barriers. The study of the mechanisms involved in the permeation process, and the ways to control it, can make this route of drug administration cease to be a constant promise and become a reality. In this work, we address the physicochemical and biopharmaceutical aspects encountered in the pathway of drugs through the skin, and the potential added value of using solid lipid nanoparticles (SLN) and nanostructured lipid vectors (NLC) to drug permeation/penetration through this route. The technology and architecture for obtaining lipid nanoparticles are described in detail, namely the composition, production methods and the ability to release pharmacologically active substances, as well as the application of these systems in the vectorization of various pharmacologically active substances for dermal and transdermal applications. The characteristics of these systems in terms of dermal application are addressed, such as biocompatibility, occlusion, hydration, emollience and the penetration of pharmacologically active substances. The advantages of using these systems over conventional formulations are described and explored from a pharmaceutical point of view. This article is a part of the Lipid-Based Nanoparticles Special issue.
Bioengineering, 2021
Surfactants are amphiphilic compounds having hydrophilic and hydrophobic moieties in their struct... more Surfactants are amphiphilic compounds having hydrophilic and hydrophobic moieties in their structure. They can be of synthetic or of microbial origin, obtained respectively from chemical synthesis or from microorganisms’ activity. A new generation of ecofriendly surfactant molecules or biobased surfactants is increasingly growing, attributed to their versatility of applications. Surfactants can be used as drug delivery systems for a range of molecules given their capacity to create micelles which can promote the encapsulation of bioactives of pharmaceutical interest; besides, these assemblies can also show antimicrobial properties. The advantages of biosurfactants include their high biodegradability profile, low risk of toxicity, production from renewable sources, functionality under extreme pH and temperature conditions, and long-term physicochemical stability. The application potential of these types of polymers is related to their properties enabling them to be processed by emuls...
Materials, 2021
Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for sever... more Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these “virus-sized particles” can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells’ interactions. In this review, the Comet assay is described, discussing several examples of its applicatio...
Rendiconti Lincei. Scienze Fisiche e Naturali, 2021
Medicinal plants always are part of folk medicine and are nowadays receiving worldwide attention ... more Medicinal plants always are part of folk medicine and are nowadays receiving worldwide attention for prophylaxis, management, and treatment of several diseases, as an alternative to chemical drugs. The current work provided a comprehensive overview and analysis of the Astragalus and health relationship in literature. The analysis of their therapeutic potential is thus instrumental to understand their bioactivity. Among these, the flowering medicinal plant Astragalus membranaceus has raised interest due to several beneficial health effects. This perspective review discussed the botanical, geographical, historical, and the therapeutic properties of A. membranaceus, with a special focus on its health improving effects and medicinal applications both in vitro and in vivo. Graphic abstract
Nanomaterials, 2021
Oil-in-water nanoemulsions (NEs) are considered a suitable nanotechnological approach to improve ... more Oil-in-water nanoemulsions (NEs) are considered a suitable nanotechnological approach to improve the eye-related bioavailability of lipophilic drugs. The potential of cationic NEs is prominent due to the electrostatic interaction that occurs between the positively charged droplets with the negatively charged mucins present in the tear film. This interaction offers prolonged NEs residence at the ocular surface, increasing the drug absorption. Triamcinolone acetonide (TA) is one of the first pharmacologic strategies applied as an intravitreal injection in the treatment of age-related macular degeneration (AMD). Newly synthesized quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and quinuclidine surfactants have been screened with the purpose to select the best compound to formulate long-term stable NEs that combine the best physicochemical properties for the loading of TA intended for ocular administration.
Molecules, 2020
Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be lo... more Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules and nanospheres, which are distinguished by the morphological structure. Polymeric NPs have shown great potential for targeted delivery of drugs for the treatment of several diseases. In this review, we discuss the most commonly used methods for the production and characterization of polymeric NPs, the association efficiency of the active compound to the polymeric core, and the in vitro release mechanisms. As the safety of nanoparticles is a high priority, we also discuss the toxicology and ecotoxicology of nanoparticles to humans and to the environment.
Heliyon, 2020
Sunscreens have been employed on daily skin care for centuries. Their role in protecting the skin... more Sunscreens have been employed on daily skin care for centuries. Their role in protecting the skin from sun damage, avoiding accelerated photoaging and even limiting the risk of development of skin cancer is unquestionable. Although several chemical and physical filters are approved as sunscreens for human use, their safety profile is dependent on their concentration in the formulation which governs their acceptance by the regulatory agencies. A strategic delivery of such molecules should provide a UV protection and limit the skin penetration. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) may offer an alternative approach to achieve a synergistic effect on the UV protection when loaded with sunscreens as particles themselves also have a UV light scattering effect. Besides, the lipid character of SLN and NLC improves the encapsulation of lipophilic compounds, with enhanced loading capacity. Silica nanoparticles have also been employed in sunscreen formulations. Due to the formed sol-gel complexes, which covalently entrap sunscreen molecules, a controlled release is also achieved. In the present work, we have developed a new sunscreen formulation composed of hybrid SLN-Silica particles loaded with octyl methoxycinnamate (Parsol ® MCX), and their further incorporation into a hydrogel for skin administration. Hybrid SLN-silica particles of 210.0 AE 3.341 nm of mean size, polydispersity below 0.3, zeta potential of ca. |7| mV, loading capacity of 19.9% and encapsulation efficiency of 98.3% have been produced. Despite the slight negative surface charge, the developed hybrid nanoparticles remained physicochemically stable over the study period. Turbiscan transmission profiles confirmed the colloidal stability of the formulations under stress conditions. The texture profile analysis of Parsol-SLN and Parsol-SLN-Si revealed semisolid properties (e.g. adhesiveness, hardness, cohesiveness, springiness, gumminess, chewiness, resilience) suitable for topical application, together with the bioadhesiveness in the skin of pig ears. The non-irritation profile of the hybrid nanoparticles before and after dispersion into Carbopol hydrogels was confirmed by HET-CAM test.
Forests, 2020
Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cos... more Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cost-effective production when compared to chemical drugs, encouraging researchers to further exploit the therapeutic potential of the former. One of the most popular medicinal plants is Vitex agnus-castus L., grown in tropical and sub-tropical regions, to which different health benefits have already been attributed. In this perspective article, the in vitro and in vivo therapeutic properties of V. agnus-castus L. have been analyzed and reviewed with a special focus on its health-promoting effects and potential nutraceutical applications.
Molecules, 2020
Carnitine can be considered a conditionally essential nutrient for its importance in human physio... more Carnitine can be considered a conditionally essential nutrient for its importance in human physiology. This paper provides an updated picture of the main features of carnitine outlining its interest and possible use. Particular attention has been addressed to its beneficial properties, exploiting carnitine’s properties and possible use by considering the main in vitro, in animal, and human studies. Moreover, the main aspects of carnitine-based dietary supplements have been indicated and defined with reference to their possible beneficial health properties.
Materials, 2020
Photodynamic therapy is an innovative treatment approach broadly directed towards oncological dis... more Photodynamic therapy is an innovative treatment approach broadly directed towards oncological diseases. Its applicability and efficiency are closely related to the interaction of three main components, namely a photosensitizer, light and molecular triplet oxygen, which should drive cell death. Recently, several studies have demonstrated that squaraine cyanine dyes have a set of photophysical and photochemical properties that have made of these compounds’ potential photosensitizers for this therapeutic modality. In the present research work, we describe the synthesis and characterization of four quinoline- and benzoselenazole-derived unsymmetrical squaraine cyanine dyes. Except for the precursor of aminosquaraine dyes, i.e., O-methylated derivative, all dyes were evaluated for their behavior and absorption capacity in different organic and aqueous solvents, their ability to form singlet oxygen, their light-stability, and in vitro phototherapeutic effects against two human breast canc...
Applied Sciences, 2020
Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chr... more Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes. Studies in animal models and patients with diabetes have shown a high expression of the inflammatory molecules that are involved in the progression of diabetic retinopathy. Uveal melanoma is an eye tumour that remains highly deadly, because despite the correct treatment, it still causes metastasis in about 50% of patients. This type of tumour has the ability to produce and store melanin, which may result in resistance to therapy. Over time there has been development of new therapies for this disease, such as radiotherapy and surgical resection. In this review, we discuss diabetic retinopathy and ocular melanoma, their relationship with angiogenesis and the current anti-angiogenic therapies for their treatment.
Nanomaterials, 2020
Metal-based nanoparticles have been extensively investigated for a set of biomedical applications... more Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while...
Pathogens, 2019
The incidence of neglected diseases in tropical countries, such as Leishmaniasis and Chagas’s dis... more The incidence of neglected diseases in tropical countries, such as Leishmaniasis and Chagas’s disease, is attributed to a set of biological and ecological factors associated with the socioeconomic context of developing countries and with a significant burden to health care systems. Both Leishmaniasis and Chagas’s disease are caused by different protozoa and develop diverse symptoms, which depend on the specific species infecting man. Currently available drugs to treat these disorders have limited therapeutic outcomes, frequently due to microorganisms’ drug resistance. In recent years, significant efforts have been made towards the development of innovative drug delivery systems aiming to improve bioavailability and pharmacokinetic profiles of classical drug therapy. This paper discusses the key facts of Leishmaniasis and Chagas’s disease, the currently available pharmacological therapies and the new drug delivery systems for conventional drugs.