Abstract Ultraviolet B (UVB) irradiation causes free radical production, increase inflammation and oxidative stress, thus, supporting the use of antioxidants by topical administration as therapeutic approaches. Quercetin (QC) is a... more
Abstract Ultraviolet B (UVB) irradiation causes free radical production, increase inflammation and oxidative stress, thus, supporting the use of antioxidants by topical administration as therapeutic approaches. Quercetin (QC) is a flavonoid with antioxidant activity, however, high liposolubility makes it difficult to remain in the viable skin layer. Thus, this study evaluated whether microencapsulation of QC would enhance its activity in comparison with the same dose of free QC (non-active dose) and unloaded-microcapsules added in formulation for topical administration in a mouse model of UVB irradiation targeting the skin. Topical formulation containing Quercetin-loaded microcapsules (TFcQCMC) presents physico-chemical (colour, consistence, phase separation and pH) and functional antioxidant stability at 4 °C, room temperature and 40 °C for 6 months. TFcQCMC inhibited the UVB-triggered depletion of antioxidants observed by GSH (reduced glutathione), ability to reduce iron, ability to scavenge 2,2’-azinobis radical and catalase activity. TFcQCMC also inhibited markers of oxidation (lipid hydroperoxides and superoxide anion production). Concerning inflammation, TFcQCMC reduced the production of inflammatory cytokines, matrix metalloproteinase-9 activity, skin edoema, collagen fibre damage, myeloperoxidase activity/neutrophil recruitment, mast cell and sunburn cell counts. The pharmacological activity of TFcQCMC was not shared by the same pharmaceutical form containing the same dose of free QC or unloaded control microcapsules.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Abstract Topical application of drugs is the choice route of administration for treating skin diseases. The stratum corneum, a natural skin barrier, protects the body against external agents but also limits penetration of topically... more
Abstract Topical application of drugs is the choice route of administration for treating skin diseases. The stratum corneum, a natural skin barrier, protects the body against external agents but also limits penetration of topically applied drugs into deeper skin layers. Nanoparticles are nano-sized drug delivery systems with several advantages for topical administration, including protection against drug degradation and sustained drug delivery, leading to a more effective and less toxic treatment, compared to conventional topically applied formulations. Nanoparticle interactions and distribution within the skin, whether associated or not with physical methods like iontophoresis, modifies drugs penetration. It is, consequently, important to evaluate nanoparticle characteristics which bring about these interactions. Therefore, this chapter will address nanoparticle characteristics affecting skin drug penetration, their possible penetration pathways, in addition to in vitro and in vivo techniques commonly used in assessing penetration and distribution of drugs into the skin when nanoparticles are used as topical delivery systems.
Research Interests:
Research Interests:
Research Interests:
Targeted therapy has been recently highlighted due to the reduction of side effects and improvement in overall efficacy and survival from different types of cancers. Considering the approval of many monoclonal antibodies in the last... more
Targeted therapy has been recently highlighted due to the reduction of side effects and improvement in overall efficacy and survival from different types of cancers. Considering the approval of many monoclonal antibodies in the last twenty years, cancer treatment can be accomplished by the combination of monoclonal antibodies and small molecule chemotherapeutics. Thus, strategies to combine both drugs in a single administration system are relevant in the clinic. In this context, two strategies are possible and will be further discussed in this review: antibody-drug conjugates (ADCs) and antibody-functionalized nanoparticles. First, it is important to better understand the possible molecular targets for cancer therapy, addressing different antigens that can selectively bind to antibodies. After selecting the best target, ADCs can be prepared by attaching a cytotoxic drug to an antibody able to target a cancer cell antigen. Briefly, an ADC will be formed by a monoclonal antibody (MAb), a cytotoxic molecule (cytotoxin) and a chemical linker. Usually, surface-exposed lysine or the thiol group of cysteine residues are used as anchor sites for linker-drug molecules. Another strategy that should be considered is antibody-functionalized nanoparticles. Basically, liposomes, polymeric and inorganic nanoparticles can be attached to specific antibodies for targeted therapy. Different conjugation strategies can be used, but nanoparticles coupling between maleimide and thiolated antibodies or activation with the addition of ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/ N-hydroxysuccinimide (NHS) (1:5) and further addition of the antibody are some of the most used strategies. Herein, molecular targets and conjugation strategies will be presented and discussed to better understand the in vitro and in vivo applications presented. Also, the clinical development of ADCs and antibody-conjugated nanoparticles are addressed in the clinical development section. Finally, due to the innovation related to the targeted therapy, it is convenient to analyze the impact on patenting and technology. Information related to the temporal evolution of the number of patents, distribution of patent holders and also the number of patents related to cancer types are presented and discussed. Thus, our aim is to provide an overview of the recent developments in immunoconjugates for cancer targeting and highlight the most important aspects for clinical relevance and innovation.
Research Interests:
Research Interests:
Nanoparticles have been extensively employed to deliver many drugs, including siRNA, for the treatment of a variety of diseases, particularly cancer. Lately, there has been a great deal of effort to design nanoparticles with materials... more
Nanoparticles have been extensively employed to deliver many drugs, including siRNA, for the treatment of a variety of diseases, particularly cancer. Lately, there has been a great deal of effort to design nanoparticles with materials that are able to respond to intrinsic or extrinsic stimuli for "on…
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Biophysics, Chemistry, Biomedical Engineering, Fluorescence, Medicine, and 15 moreHumans, Controlled release, Lipid Membranes, PMC, Case Study, Animals, Skin, Swine, Fluorescent probes, Enhancer, Transdermal, Skin Absorption, fluorescent dyes, Pharmacology and pharmaceutical sciences, and design principle
Research Interests:
Squamous cell carcinoma (SCC) is a malignant tumor in which epidermal growth factor receptor (EGFR) overexpression is associated with poor prognosis and malignancy. For SCC treatment, cetuximab, an anti-EGFR antibody, is administered in... more
Squamous cell carcinoma (SCC) is a malignant tumor in which epidermal growth factor receptor (EGFR) overexpression is associated with poor prognosis and malignancy. For SCC treatment, cetuximab, an anti-EGFR antibody, is administered in combination with a chemotherapeutic drug for improved efficacy. In this work, an EGFR-targeted immunoliposome loaded with 5-fluorouracil (5- FU) was developed to allow co-administration of the antibody and the chemotherapeutic agent and selective delivery to SCC cells. Topically applied iontophoresis and subcutaneous injections of the 5-FU-loaded immunoliposomes were employed in an SCC xenograft animal model to evaluate the influence of the administration route on therapeutic efficacy. In vitro, cellular uptake of cetuximab-immunoliposomes by EGFR-positive SCC cells was 3.5-fold greater than the uptake of control liposomes. Skin penetration studies showed that iontophoresis of immunoliposomes doubled the 5-FU penetration into the viable epidermis com...
Research Interests:
Drug delivery is of paramount importance, since the drug needs to be delivered to a specific site, in adequate concentration, avoiding degradation in order to provide therapeutic efficacy. Different nanocarriers have been used over the... more
Drug delivery is of paramount importance, since the drug needs to be delivered to a specific site, in adequate concentration, avoiding degradation in order to provide therapeutic efficacy. Different nanocarriers have been used over the years for this purpose and liposomes are well-established systems due to the high biocompatibility and the possibility to vehiculate both hydrophilic and lipophilic drugs. In order to circumvent the rapid clearance by the reticuloendothelial system and to avoid the healthy cells exposure to the drug, long circulating liposomes containing polyethyleneglycol (PEG) and functionalized liposomes for targeted delivery have been developed. Immunoliposomes consist of liposomes containing antibodies or antibody fragments attached at the membrane surface. This attachment can be performed using PEG lipids, containing a reactive terminal group such as maleimide and thiolated antibodies. Additionaly, the use of PEG chains as spacers increases antibody-antigen affi...
Research Interests:
Delonix is a galactomannan polysaccharide extracted from the endosperm of Delonix regia plant. This study aims at the development of Delonix nanoparticle and assesses its potential for ocular delivery by evaluating its in-vitro stability,... more
Delonix is a galactomannan polysaccharide extracted from the endosperm of Delonix regia plant. This study aims at the development of Delonix nanoparticle and assesses its potential for ocular delivery by evaluating its in-vitro stability, toxicity and cellular uptake. Fluorescent nanoparticles (BODIPY-loaded nanoparticles) were prepared by a Quality-by-Design modified nanoprecipitation technique. Optimized nanoparticles had mean sizes <240nm, PdI<0.2 and zeta potential of <-30mV. Mixture of surfactants with different hydrophilic-lipophilic balance controlled nanoparticle swelling. Nanoparticles, which were stable in the presence of simulated lachrymal fluid and lysozyme also sustained the release of BODIPY. In-vitro studies suggest no toxicity of the nanoparticles in concentration range of 100-1483.3μg/mL on retinal and corneal epithelial cells. Flow cytometry and confocal microscopy techniques showed that retinal cells but not corneal cells, uptake 18% of the nanoparticles...
Research Interests:
Research Interests: Materials Engineering, Materials Science, Chemistry, Inorganic Chemistry, Nanoparticles, and 15 moreNanotechnology, Medicine, Lipids, Mice, Female, Animals, Skin, Iontophoresis, In Vivo, Doxorubicin, Biomedical nanotechnology, Stratum Corneum, Antineoplastic Agents, Skin Neoplasms, and Skin Absorption
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
ABSTRACT Iontophoretic delivery of a homologous series of cationic ALA esters, into and through the skin, has been detd. and compared to that of the zwitterionic parent drug. The roles of electrorepulsion and electroosmosis have been... more
ABSTRACT Iontophoretic delivery of a homologous series of cationic ALA esters, into and through the skin, has been detd. and compared to that of the zwitterionic parent drug. The roles of electrorepulsion and electroosmosis have been deduced.
Research Interests:
Research Interests: Materials Science, Drug delivery, Nanoparticles, Pharmaceutical Chemistry, Medicine, and 12 moreHumans, Animals, Drug Delivery Systems, Skin, Topical Drug Administration, Microspheres, Hair Follicle, Stratum Corneum, Pharmaceutical preparations, Transdermal, Skin Absorption, and Pharmacology and pharmaceutical sciences
Vegetable oils offer excellent biological properties, but their high lipophilicity limits their bioavailability. This work aimed to develop nanoemulsions based on sunflower and rosehip oils and to evaluate their wound-healing activity.... more
Vegetable oils offer excellent biological properties, but their high lipophilicity limits their bioavailability. This work aimed to develop nanoemulsions based on sunflower and rosehip oils and to evaluate their wound-healing activity. The influence of phospholipids of plant origin on nanoemulsions’ characteristics was investigated. A nanoemulsion prepared with a mixture of phospholipids and synthetic emulsifiers (Nano-1) was compared with another prepared only with phospholipids (Nano-2). The healing activity was evaluated in wounds induced in human organotypic skin explant culture (hOSEC) based on histological and immunohistochemical analysis. The hOSEC wound model was validated, showing that high nanoparticle concentration in the wound bed interferes with cell mobility and the ability to respond to the treatment. Nanoemulsions were 130 to 370 nm, with a concentration of 1013 particles/mL, and a low potential to induce inflammatory processes. Nano-2 was three times larger than Nan...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Permeation assays are important for the development of topical formulations applied on buccal mucosa. Swine buccal and esophageal epithelia are usually used as barriers for these assays, while frozen epithelia have been used to optimize... more
Permeation assays are important for the development of topical formulations applied on buccal mucosa. Swine buccal and esophageal epithelia are usually used as barriers for these assays, while frozen epithelia have been used to optimize the experimental setup. However, there is no consensus on these methods. In transdermal studies, barrier integrity has been evaluated by measuring electrical resistance (ER) across the skin, which has been demonstrated to be a simple, fast, safe, and cost-effective method. Therefore, the aims here were to investigate whether ER might also be an effective method to evaluate buccal and esophageal epithelium mucosa integrity for in vitro permeation studies, and to establish a cut-off ER value for each epithelium mucosa model. We further investigated whether buccal epithelium could be substituted by esophageal epithelium in transbuccal permeation studies, and whether their permeability and integrity were affected by freezing at −20 °C for 3 weeks. Fresh ...
Research Interests:
Research Interests:
A Bronquite infecciosa Aviaria (BI) e uma doenca de distribuicao mundial, causada pelo virus da bronquite infecciosa (VBI). A enfermidade provoca grandes prejuizos economicos na avicultura industrial, acometendo aves de postura e de corte... more
A Bronquite infecciosa Aviaria (BI) e uma doenca de distribuicao mundial, causada pelo virus da bronquite infecciosa (VBI). A enfermidade provoca grandes prejuizos economicos na avicultura industrial, acometendo aves de postura e de corte de todas as idades. Em busca de adjuvantes de nova geracao para a formulacao de vacinas inativadas contra as variantes de campo do VBI, o trabalho teve como objetivo desenvolver e avaliar a eficacia de uma vacina inativada com uma variante brasileira do VBI encapsulada em nanoparticulas de quitosana e administrada via oculo-nasal (VBI-CS-ON) em aves SPF. Foi utilizada a tecnica de geleificacao ionica para a formulacao das nanoparticulas com o VBI. Para comparar o grau de protecao induzido pela vacina de nanoparticulas, outra vacina inativada convencional contra o VBI foi utilizada, na qual foi incorporada um adjuvante oleoso e se usou a administracao pela via intra-muscular (VBI-O-IM). Para a infeccao experimental foram utilizadas 54 aves, distribu...
Research Interests: Physics()
()
In acne management, oral isotretinoin (IST) is associated with various untoward systemic effects, while its topical formulation has irritation side effects.Delonix(DLX) is a natural galactomannan derived fromDelonix regiaseed that can... more
In acne management, oral isotretinoin (IST) is associated with various untoward systemic effects, while its topical formulation has irritation side effects.Delonix(DLX) is a natural galactomannan derived fromDelonix regiaseed that can fabricate nanoparticles for topical skin delivery. This study aims to develop IST-DLX nanoparticles and assess their prospects for acne treatment. Fluorescent-DLX nanoparticles (made with a lipophilic BODIPY dye) or IST-DLX nanoparticles were prepared and characterized. BODIPY-DLX nanoparticles' skin distribution and IST-DLX nanoparticles'in-vitrotargeting were assessed in pig ear skin, inflammatory modulation was assessed in AMJ-2 macrophage cells, while skin penetration and irritation were assessed in Wistar rats. IST-DLX nanoparticles had ≈230 nm, negative zeta potential, and ≈30% encapsulation efficiency. Confocal showed BODIPY in DLX nanoparticles accumulated in hair follicles as compared to BODIPY solution. IST-DLX nanoparticles released ≈37% IST over 48 h and increased IST 3-fold in hair follicles compared to IST solution. IST-DLX nanoparticles suppressed IL-6 expression in cells and reduced photo-irritation in Wistar rats compared to IST solution. In conclusion, IST-DLX nanoparticles may target and deliver adequate IST to skin layers associated with acne, avoid systemic penetration, modulate inflammatory pathogenic acne stage and prevent IST topical photo-irritation.
Research Interests:
Research Interests:
The encapsulation process of the PdII complex [PdCl(PPh3)(PrCh)], a promising cytotoxic agent on ovarian cancer cells, in PLGA polymer was studied. The cytotoxicity results showed that the formulation led to a significant reduction of the... more
The encapsulation process of the PdII complex [PdCl(PPh3)(PrCh)], a promising cytotoxic agent on ovarian cancer cells, in PLGA polymer was studied. The cytotoxicity results showed that the formulation led to a significant reduction of the ovarian cell viability (80% at 1 μM).
Research Interests:
Research Interests:
Lipophilic drugs do not usually benefit from iontophoresis mainly because they do not solubilize in aqueous formulations suitable for the application of electric current. To explore the influence of iontophoresis on penetration of these... more
Lipophilic drugs do not usually benefit from iontophoresis mainly because they do not solubilize in aqueous formulations suitable for the application of electric current. To explore the influence of iontophoresis on penetration of these drugs, a cationic nanoemulsion was developed to solubilize zinc phthalocyanine (ZnPc), a promising drug for the treatment of skin cancer. To verify the influence of particle size on iontophoresis, an emulsion of nanoemulsion-like composition was also developed. The formulations were characterized and cutaneous and tumor penetration studies were performed in vitro and in vivo, respectively. With particles of about 200 nm, the nanoemulsion solubilized 2.5-fold more ZnPc than the 13-µm emulsion. At the same concentration of ZnPc, in vitro passive penetration studies showed that the nanoemulsion increased, after 1 h of treatment, by almost 4 times the penetration of ZnPc into the viable layers of the skin when compared to the emulsion, whereas iontophore...