



@article {3390,
	title = {Are coffee silverskin extracts safe for topical use? An in vitro and in vivo approach},
	journal = {Industrial Crops and Products},
	volume = {63},
	year = {2015},
	note = {Times Cited: 0},
	month = {2015},
	pages = {167-174},
	isbn = {0926-6690},
	url = {<Go to ISI>://WOS:000347499000025},
	author = {Rodrigues, F. and Pereira, C. and Pimentel, F. B. and Alves, R. C. and Ferreira, M. and Sarmento, B. and Helena Amaral, M. and Oliveira, M. Beatriz P. P.}
}
@article {3299,
	title = {Actively targeted cetuximab conjugated γ-poly(glutamic acid)-docetaxel nanomedicines for epidermal growth factor receptor over expressing colon cancer cells},
	journal = {Journal of Biomedical Nanotechnology},
	volume = {10},
	year = {2014},
	note = {Cited By (since 1996):1Export Date: 21 November 2014},
	month = {2014},
	pages = {1416 - 1428},
	abstract = {Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded γ-poly (glutamic acid) (γ-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-γ-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-γ-PGA NPs over DTXL-γ-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-γ-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-γ-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-γ-PGA Nps (targeted) and ICG-DTXL-γ-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-γ-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer. Copyright {\textcopyright} 2014 American Scientific Publishers All rights reserved.},
	keywords = {Cetuximab, colon cancer, Docetaxel, Epidermal growth factor receptor, Poly(γ-glutamic acid) nanoparticles, Targeted nanomedicines},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899683740\&partnerID=40\&md5=39d65057952b3e192590262631867971},
	author = {Maya, S. and Sarmento, B. and Lakshmanan, V.-K. and Menon, D. and Jayakumar, R.}
}
@article {3275,
	title = {Biodistribution and pharmacokinetics of Dapivirine-loaded nanoparticles after vaginal delivery in mice},
	journal = {Pharmaceutical Research},
	volume = {31},
	year = {2014},
	note = {Cited By (since 1996):2Export Date: 21 November 2014},
	month = {2014},
	pages = {1834 - 1845},
	abstract = {Purpose: To assess the potential of polymeric nanoparticles (NPs) to affect the genital distribution and local and systemic pharmacokinetics (PK) of the anti-HIV microbicide drug candidate dapivirine after vaginal delivery. Methods: Dapivirine-loaded, poly(ethylene oxide)-coated poly(epsilon-caprolactone) (PEO-PCL) NPs were prepared by a nanoprecipitation method. Genital distribution of NPs and their ability to modify the PK of dapivirine up to 24 h was assessed after vaginal instillation in a female mouse model. Also, the safety of NPs upon daily administration for 14 days was assessed by histological analysis and chemokine/cytokine content in vaginal lavages. Results: PEO-PCL NPs (180-200 nm) were rapidly eliminated after administration but able to distribute throughout the vagina and lower uterus, and capable of tackling mucus and penetrate the epithelial lining. Nanocarriers modified the PK of dapivirine, with higher drug levels being recovered from vaginal lavages and vaginal/lower uterine tissues as compared to a drug suspension. Systemic drug exposure was reduced when NPs were used. Also, NPs were shown safe upon administration for 14 days. Conclusions: Dapivirine-loaded PEO-PCL NPs were able to provide likely favorable genital drug levels, thus attesting the potential value of using this vaginal drug delivery nanosystem in the context of HIV prophylaxis. {\textcopyright} 2014 Springer Science+Business Media New York.},
	keywords = {HIV/AIDS, microbicides, poly(ε-caprolactone), pre-exposure prophylaxis, vaginal drug delivery},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84904252215\&partnerID=40\&md5=e50091fa44bc3ac794251baa9e57d736},
	author = {Das Neves, J. and Ara{\'u}jo, F. and Andrade, F. and Amiji, M. and Bahia, M.F. and Sarmento, B.}
}
@article {3300,
	title = {Chitosan cross-linked docetaxel loaded EGF receptor targeted nanoparticles for lung cancer cells},
	journal = {International Journal of Biological Macromolecules},
	volume = {69},
	year = {2014},
	note = {Cited By (since 1996):1Export Date: 21 November 2014},
	month = {2014},
	pages = {532 - 541},
	abstract = {Lung cancer, associated with the up-regulated epidermal growth factor receptor (EGFR) led to the development of EGFR targeted anticancer therapeutics. The biopolymeric nanoparticles form an outstanding system for the targeted delivery of therapeutic agents. The present work evaluated the in vitro effects of chitosan cross-linked γ-poly(glutamic acid) (γ-PGA) nanoparticles (Nps) loaded with docetaxel (DTXL) and decorated with Cetuximab (CET), targeted to EGFR over-expressing non-small-cell-lung-cancer (NSCLC) cells (A549). CET-DTXL-γ-PGA Nps was prepared by ionic gelation and CET conjugation via EDC/NHS chemistry. EGFR specificity of targeted Nps was confirmed by the higher uptake rates of EGFR +ve A549 cells compared to that of EGFR -ve cells (NIH3T3). The cytotoxicity of Nps quantified using cell based (MTT/LDH) and flowcytometry (Cell-cycle analysis, Annexin V/PI and JC-1) assays showed superior antiproliferative activity of CET-DTXL-γ-PGA Nps over DTXL-γ-PGA Nps. The A549 cells treated with CET-DTXL-γ-PGA NPs underwent a G2/M phase cell cycle arrest followed by reduction in mitochondrial membrane potential of A549 cells, inducing apoptosis and necrosis resulting in enhanced cancer cell death. CET-DTXL-γ-PGA Nps exhibited enhanced cellular internalization and therapeutic activity, by actively targeting EGFR on NSCLC cells and hence could be an effective alternative to non-specific, conventional chemotherapy by increasing its efficiency by many folds. {\textcopyright} 2014 Elsevier B.V.},
	keywords = {Cetuximab, chitosan, Epidermal growth factor receptor, Poly(γ-glutamic acid) nanoparticles, Targeted nanoparticles},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903523289\&partnerID=40\&md5=728cbd3502e7922319f5f88fa8d6ec6d},
	author = {Maya, S. and Sarmento, B. and Lakshmanan, V.-K. and Menon, D. and Seabra, V. and Jayakumar, R.}
}
@article {3322,
	title = {Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers},
	journal = {Biomaterials},
	volume = {35},
	year = {2014},
	note = {Cited By (since 1996):1Export Date: 21 November 2014},
	month = {2014},
	pages = {7172 - 7179},
	abstract = {Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles{\textquoteright} physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (Papp) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane. {\textcopyright} 2014 Elsevier Ltd.},
	keywords = {Cell monolayers, chitosan, Diabetes, Insulin, Microparticles, Porous silicon},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84902079022\&partnerID=40\&md5=4de20e5572512006f72e11cb61a2035c},
	author = {Shrestha, N. and Shahbazi, M.-A. and Ara{\'u}jo, F. and Zhang, H. and M{\"a}kil{\"a}, E.M. and Kauppila, J. and Sarmento, B. and Salonen, J.J. and Hirvonen, J.T. and Santos, H.A.}
}
@article {3294,
	title = {Eradication of Helicobacter pylori: Past, present and future},
	journal = {Journal of Controlled Release},
	volume = {189},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {169 - 186},
	abstract = {Helicobacter pylori is the major cause of chronic gastritis and peptic ulcers. Since the classification as a group 1 carcinogenic by International Agency for Research on Cancer, the importance of the complete H. pylori eradication has obtained a novel meaning. Hence, several studies have been made in order to deepen the knowledge in therapy strategies. However, the current therapy presents unsatisfactory eradication rates due to the lack of therapeutic compliance, antibiotic resistance, the degradation of antibiotics at gastric pH and their insufficient residence time in the stomach. Novel approaches have been made in order to overcome these limitations. The purpose of this review is to provide an overview about the current therapy and its limitations, while highlighting the possibility of using micro- and nanotechnology to develop gastric drug delivery systems, overcoming these difficulties in the future. {\textcopyright} 2014 Elsevier B.V.},
	keywords = {Drug delivery, Helicobacter pylori, Microparticles, nanoparticles, Treatment},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84904904149\&partnerID=40\&md5=96cfe2d7f96a7c7a16bb7eb733c2b71c},
	author = {Lopes, D. and Nunes, C. and Martins, M.C.L. and Sarmento, B. and Reis, S.}
}
@article {3271,
	title = {An evaluation of the latest in vitro tools for drug metabolism studies},
	journal = {Expert Opinion on Drug Metabolism and Toxicology},
	volume = {10},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {103 - 119},
	abstract = {Introduction: Drugs are indispensable for human welfare nevertheless there is a lack of safe drugs. Obtaining pharmacokinetics information, especially metabolism, is a requirement during preclinical and clinical drug development so that in vitro tools represent a simple path where it is possible to assess drug toxicity and predict drug safety in humans. Areas covered: This review covers the latest in vitro tools developed for assessing drug toxicity in different organs. A special focus is given to hepatic models, as it is the main organ responsible for drug metabolism and consequently bioactivation and detoxification reactions. Three-dimensional culture models have been widely developed, resembling in vivo-like conditions, and are also discussed in this review. Expert opinion: Several in vitro tools to assess hepatic drug metabolism have been developed, however, novel in vitro methods to investigate extra-hepatic drug metabolism still need to be improved. These methods are able to reduce the number of animal used in preclinical experiments, but in vivo tests are mandatory for drug approval and commercialization. {\textcopyright} 2014 Informa UK, Ltd.},
	keywords = {Hepatic metabolism, in vitro models, Intestinal metabolism, Pulmonary metabolism, Renal metabolism},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84890346695\&partnerID=40\&md5=24208bee91a909d1e0e4882b6f2da4b6},
	author = {Costa, A. and Sarmento, B. and Seabra, V.}
}
@article {3264,
	title = {The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium},
	journal = {Biomaterials},
	volume = {35},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {9199 - 9207},
	abstract = {Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability invitro. All the nanoparticles presented a size of approximately 200nm. The nanoparticles{\textquoteright} interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal invitro models. In conclusion, PLGA+CS and PSi+CS are promising nanocarriers for the oral delivery of GLP-1. {\textcopyright} 2014 Elsevier Ltd.},
	keywords = {chitosan, Diabetes, Glucagon like peptide-1, nanoparticles, Oral delivery systems, Triple co-culture},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84906788144\&partnerID=40\&md5=38c557a51eb271561ef59bfe12421842},
	author = {Ara{\'u}jo, F. and Shrestha, N. and Shahbazi, M.-A. and Fonte, P. and M{\"a}kil{\"a}, E.M. and Salonen, J.J. and Hirvonen, J.T. and Granja, P.L. and Santos, H.A. and Sarmento, B.}
}
@article {3279,
	title = {In vitro intestinal absorption of amino acid mixtures extracted from codfish (Gadus morhua L.) salting wastewater},
	journal = {International Journal of Food Science and Technology},
	volume = {49},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {27 - 33},
	abstract = {Summary: This study reports on the intestinal permeability of salt-containing mixtures of amino acids extracted from codfish salting wastewater. Permeability was evaluated in vitro using the Caco-2 cell line model; cell integrity during exposure to mixtures of amino acids was estimated by measuring the transepithelial electrical resistance (TEER). The effect of salt (NaCl) on the permeability and on the intestinal cell{\textquoteright}s integrity was also examined. Permeation rate (i.e. transport) was >=95\% for all amino acids except for creatine, for which it was 6\%. Values for apparent permeability coefficients, Papp \&gt; 10-5 cm s-1, for mixture with isotonic concentration of NaCl suggest that amino acids are very likely to be absorbed in humans. Mixture with a hypertonic level of NaCl exerts a cytotoxic effect in intestinal cells resulting in a loss of epithelium integrity. Results show that isotonic mixture of amino acids extracted from codfish salting wastewater could be used in food, feed, cosmetic and pharmaceutical formulations. These applications could contribute to the fish industry sustainability. {\textcopyright} 2013 Institute of Food Science and Technology.},
	keywords = {Absorption, Amino acids, Caco-2 cell, Codfish, Small intestine},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84890426132\&partnerID=40\&md5=2727df048ef513e5a6a2978cfe149092},
	author = {Ferraro, V. and Ferreira Jorge, R. and Cruz, I.B. and Antunes, F. and Sarmento, B. and Castro, P.M.L. and Pintado, M.E.}
}
@article {3304,
	title = {Mad2 checkpoint gene silencing using epidermal growth factor receptor-targeted chitosan nanoparticles in non-small cell lung cancer model},
	journal = {Molecular Pharmaceutics},
	volume = {11},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {3515 - 3527},
	abstract = {RNA interference has emerged as a powerful strategy in cancer therapy because it allows silencing of specific genes associated with tumor progression and resistance. Mad2 is an essential mitotic checkpoint component required for accurate chromosome segregation during mitosis, and its complete abolition leads to cell death. We have developed an epidermal growth factor receptor (EGFR)-targeted chitosan system for silencing the Mad2 gene as a strategy to efficiently induce cell death in EGFR overexpressing human A549 non-small cell lung cancer cells. Control and EGFR-targeted chitosan nanoparticles loaded with small interfering RNAs (siRNAs) against Mad2 were formulated and characterized for size, charge, morphology, and encapsulation efficiency. Qualitative and quantitative intracellular uptake studies by confocal imaging and flow cytometry, respectively, showed time-dependent enhanced and selective intracellular internalization of EGFR-targeted nanoparticles compared to nontargeted system. Targeted nanoparticles showed nearly complete depletion of Mad2 expression in A549 cells contrasting with the partial depletion in the nontargeted system. Accordingly, Mad2-silencing-induced apoptotic cell death was confirmed by cytotoxicity assay and flow cytometry. Our results demonstrate that EGFR-targeted chitosan loaded with Mad2 siRNAs is a potent delivery system for selective killing of cancer cells.},
	keywords = {chitosan nanoparticles, Epidermal growth factor receptor, Mad2 gene, non-small cell lung cancer, RNA interference, tumor targeting},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84908009342\&partnerID=40\&md5=bc0130ca0bcdb576b7de6801c3517e93},
	author = {Nascimento, A.V. and Singh, A. and Bousbaa, H. and Ferreira, D. and Sarmento, B. and Amiji, M.M.}
}
@article {3286,
	title = {Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system},
	journal = {International Journal of Nanomedicine},
	volume = {9},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {1757 - 1769},
	abstract = {Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood-brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretro-viral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood-brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS. {\textcopyright} 2014 Gomes et al.},
	keywords = {Blood-brain barrier, drug targeting, Efflux transporters, HIV/AIDS, Protease inhibitors},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84898486385\&partnerID=40\&md5=31d2c7f6e0759fb62143e329fb8599ae},
	author = {Gomes, M.J. and Das Neves, J. and Sarmento, B.}
}
@article {3269,
	title = {Optimization of the production of solid Witepsol nanoparticles loaded with rosmarinic acid},
	journal = {Colloids and Surfaces B: Biointerfaces},
	volume = {115},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {109 - 117},
	abstract = {During the last decade there has been a growing interest in the formulation of new food and nutraceutical products containing compounds with antioxidant activity. Unfortunately, due to their structure, certain compounds such as polyphenols, in particular rosmarinic acid (RA) are not stable and may interact easily with matrices in which they are incorporated. To overcome such limitations, the formulation of loaded polyphenols nanoparticles can offer an efficient solution to protect such compounds. Based on this rationale, the aim of this study was to prepare solid lipid nanoparticles (SLNs) loaded with RA using a hot melt ultrasonication method, where Witepsol H15 was used as lipid and Polysorbate 80 (Tween 80) as surfactant, following a 32 fractional factorial design, resulting in the use of 3 different percentages of surfactant (viz. 1, 2 and 3\%, v/v) and lipid (0.5, 1.0 and 1.5\%, w/v). The stability of the nanoparticles systems were tested during 28d in aqueous solution stored at refrigeration temperature (ca. 5{\textdegree}C), tracking the mean particle size of different formulations by photon correlation spectroscopy. To confirm RA entrapment, thermal analyses of the nanoparticles by DSC and FTIR were performed. The association efficiencies percentages (AE\%) were determined using HPLC to quantitatively assess the RA in supernatants. Results showed that Witepsol H15 produced nanoparticles with initial mean diameters between 270 and 1000nm, yet over time, a slight increase occurred, but without occurrence of aggregation. The AE\% showed a high percentage of encapsulation (ca. 99\%), which reveals low polyphenol releases from SLNs throughout storage time. In general, results showed a successful production of SLNs with properties that can be used to food applications. {\textcopyright} 2013 Elsevier B.V.},
	keywords = {Optimization, Rosmarinic acid, SLNs, Witepsol},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84892548596\&partnerID=40\&md5=231718083d6238d5ac676d642e12b0f8},
	author = {Campos, D.A. and Madureira, A.R. and Gomes, A.M. and Sarmento, B. and Pintado, M.M.}
}
@article {3281,
	title = {Stability study perspective of the effect of freeze-drying using cryoprotectants on the structure of insulin loaded into PLGA nanoparticles},
	journal = {Biomacromolecules},
	volume = {15},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {3753 - 3765},
	abstract = {This work aimed to evaluate the influence of a freeze-drying process using different cryoprotectants on the structure of insulin loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles and to assess the stability of these nanoparticles upon 6 months of storage following ICH guidelines. Insulin-loaded PLGA nanoparticles with a size around 450 nm were dehydrated using a standard freeze-drying cycle, using trehalose, glucose, sucrose, fructose, and sorbitol at 10\% (w/v) as cryoprotectants. All formulations, except those nonadded of cryoprotectant and added with trehalose, collapsed after freeze-drying. The addition of cryoprotectants increased the nanoparticles stability upon storage. FTIR results showed that insulin maintained its structure after encapsulation in about 88\%, decreasing to 71\% after freeze-drying. The addition of cryoprotectants prior to freeze-drying increased insulin structural stability an average of up to 79\%. Formulations collapsed after freeze-drying showed better protein stabilization upon storage, in special sorbitol added formulation, preserving 76, 80, and 78\% of insulin structure at 4 {\textdegree}C, 25 {\textdegree}C/60\% RH, and 40 {\textdegree}C/75\% RH, respectively. Principal component analysis also showed that the sorbitol-added formulation showed the most similar insulin structural modifications among the tested storage conditions. These findings suggested that regarding nanoparticles stability, cryoprotectants are versatile to be used in a standard freeze-drying, however they present different performances on the stabilization of the loaded protein. Thus, on the freeze-drying of the nanoparticles field, this work gives rise to the importance of the process of optimization, searching for a balance between a good obtainable cake with an optimal structural stabilization of the loaded protein.},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84907968489\&partnerID=40\&md5=15b0a74cf97f04ed887f86b7ad1c45a2},
	author = {Fonte, P. and Soares, S. and Sousa, F. and Costa, A. and Seabra, V. and Reis, S. and Sarmento, B.}
}
@article {3317,
	title = {Study of the isoflavone content of different extracts of Medicago spp. as potential active ingredient},
	journal = {Industrial Crops and Products},
	volume = {57},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	pages = {110 - 115},
	abstract = {This study focuses on the isoflavones composition of different extracts of Medicago species (M. minima, M. tornata, M. truncatula, M. rigidula, M. scutelata, M. segitalis and M. sativa), a leguminous crop used as animal feeding. There are some research studies on the isoflavones composition of Medicago sativa, but no comprehensive profile of isoflavones has been reported for these other six species. In this work, two glycosides (daidzin and genistin) and six aglycones (daidzein, glycitein, genistein, formononetin, prunetin and biochanin A) were determined by high performance liquid chromatography (HPLC/DAD) in three different extracts of these species: aqueous, hydroalcoholic and alcoholic. In all samples genistin, daidzein and genistein were the most abundant isoflavone compounds. The highest concentration of genistin was observed in the extracts of M. scutelata (5.2 and 9.6. mg/kg. db, respectively, for hydroalcoholic and alcoholic extract), in amounts 2-4.5-fold higher than the other samples evaluated. Daidzein is also present in high amounts in M. scutelata (19.2. mg/kg. db, alcoholic extract). Genistein is detected in several species at concentrations ranging from 0.7 (aqueous extract of M. tornata) to 16.1. mg/kg. db (alcoholic extract of M. scutelata). In terms of total isoflavones content per species, results showed significant differences between M. rigidula and M. sativa, considering all type of solvents, being the highest and the lowest one, respectively. In a general way, the extractability of compounds significantly increased from aqueous to alcoholic extracts. The study demonstrates that some Medicago species possess an excellent potential as a source of these health promoting bioactive compounds. {\textcopyright} 2014 Elsevier B.V.},
	keywords = {By-product, Daidzein, Genistein, Genistin, Isoflavones, Medicago},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84898621595\&partnerID=40\&md5=a2c78b9a016fd634ffb0ef4dbedcde5f},
	author = {Rodrigues, F. and Almeida, I. and Sarmento, B. and Amaral, M.H. and Oliveira, M.B.P.P.}
}
@article {2846,
	title = {Assessing the physical-chemical properties and stability of dapivirine-loaded polymeric nanoparticles},
	journal = {International Journal of Pharmaceutics},
	volume = {456},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {307 - 314},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84884308158\&partnerID=40\&md5=52f91c19cbe922064bbdc786298301a0},
	author = {Das Neves, J. and Amiji, M. and Bahia, M.F. and Sarmento, B.}
}
@article {2836,
	title = {Brain targeting effect of camptothecin-loaded solid lipid nanoparticles in rat after intravenous administration},
	journal = {European Journal of Pharmaceutics and Biopharmaceutics},
	volume = {85},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {488 - 502},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84888387689\&partnerID=40\&md5=e40e0a0c4221bfbc77f793ace6e47dcd},
	author = {Martins, S.M. and Sarmento, B. and Nunes, C. and L{\'u}cio, M. and Reis, S. and Ferreira, D.C.}
}
@article {2869,
	title = {Cetuximab conjugated O-carboxymethyl chitosan nanoparticles for targeting EGFR overexpressing cancer cells},
	journal = {Carbohydrate Polymers},
	volume = {93},
	year = {2013},
	note = {Cited By (since 1996):1Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {661 - 669},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874136100\&partnerID=40\&md5=71075b389cbeb450f68caf7cbb271c08},
	author = {Maya, S. and Kumar, L.G. and Sarmento, B. and Sanoj Rejinold, N. and Menon, D. and Nair, S.V. and Jayakumar, R.}
}
@article {2837,
	title = {Development and validation method for simultaneous quantification of phenolic compounds in natural extracts and nanosystems},
	journal = {Phytochemical Analysis},
	volume = {24},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {638 - 644},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84886723210\&partnerID=40\&md5=eb1de8e3010b22c26b7ddd2e09eef6a7},
	author = {Da Silva, S.B. and Oliveira, A. and Ferreira, D. and Sarmento, B. and Pintado, M.}
}
@article {2834,
	title = {Development of PLGA-mannosamine nanoparticles as oral protein carriers},
	journal = {Biomacromolecules},
	volume = {14},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {4046 - 4052},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84887602933\&partnerID=40\&md5=ee1468ca288d3ca59120be3637a51b41},
	author = {Alonso-Sande, M. and Des Rieux, A. and Fievez, V. and Sarmento, B. and Delgado, A. and Evora, C. and Remu{\~n}{\'a}n-L{\'o}pez, C. and Pr{\'e}at, V. and Alonso, M.J.}
}
@article {2845,
	title = {Effect of freeze-drying, cryoprotectants and storage conditions on the stability of secondary structure of insulin-loaded solid lipid nanoparticles},
	journal = {International Journal of Pharmaceutics},
	volume = {456},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {370 - 381},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84886730036\&partnerID=40\&md5=2214d57803df6679f944d2ebba4fa477},
	author = {Soares, S. and Fonte, P. and Costa, A. and Andrade, J. and Seabra, V. and Ferreira, D. and Reis, S. and Sarmento, B.}
}
@article {2873,
	title = {Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs},
	journal = {European Journal of Pharmaceutics and Biopharmaceutics},
	volume = {83},
	year = {2013},
	note = {Cited By (since 1996):4Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {427 - 435},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84875219051\&partnerID=40\&md5=7e18e0b0ec3428fe07eee3fa109ba607},
	author = {Antunes, F. and Andrade, F. and Ara{\'u}jo, F. and Ferreira, D. and Sarmento, B.}
}
@article {2863,
	title = {Hydrolyzed galactomannan-modified nanoparticles and flower-like polymeric micelles for the active targeting of rifampicin to macrophages},
	journal = {Journal of Biomedical Nanotechnology},
	volume = {9},
	year = {2013},
	note = {Cited By (since 1996):1Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {1076 - 1087},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84877815633\&partnerID=40\&md5=d4bbcc67f9930d53201ec08dbcfce826},
	author = {Moretton, M.A. and Chiappetta, D.A. and Andrade, F. and Das Neves, J. and Ferreira, D. and Sarmento, B. and Sosnik, A.}
}
@article {2892,
	title = {The importance of antimicrobial peptides and their potential for therapeutic use in ophthalmology},
	journal = {International Journal of Antimicrobial Agents},
	volume = {41},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {5 - 10},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84871656457\&partnerID=40\&md5=ca0df69f419a89c6d0ba7d1b73fcb9d0},
	author = {Silva, N.C. and Sarmento, B. and Pintado, M.}
}
@article {2857,
	title = {In vitro and Ex Vivo evaluation of polymeric nanoparticles for vaginal and rectal delivery of the anti-HIV drug dapivirine},
	journal = {Molecular Pharmaceutics},
	volume = {10},
	year = {2013},
	note = {Cited By (since 1996):1Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {2793 - 2807},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879736868\&partnerID=40\&md5=cd7771212c94b7031331e338743b05ed},
	author = {Das Neves, J. and Ara{\'u}jo, F. and Andrade, F. and Michiels, J. and Ari{\"e}n, K.K. and Vanham, G. and Amiji, M. and Bahia, M.F. and Sarmento, B.}
}
@article {2853,
	title = {Medicago spp. extracts as promising ingredients for skin care products},
	journal = {Industrial Crops and Products},
	volume = {49},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {634 - 644},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880378375\&partnerID=40\&md5=1b60aaf1efb444f653b44800529f5ae3},
	author = {Rodrigues, F. and Palmeira-de-Oliveira, A. and Das Neves, J. and Sarmento, B. and Amaral, M.H. and Oliveira, M.B.}
}
@article {2851,
	title = {Nanotechnology and pulmonary delivery to overcome resistance in infectious diseases},
	journal = {Advanced Drug Delivery Reviews},
	volume = {65},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {1816 - 1827},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84888198111\&partnerID=40\&md5=52e53a72fbb5f199ac2416a061eeb409},
	author = {Andrade, F. and Rafael, D. and Videira, M. and Ferreira, D. and Sosnik, A. and Sarmento, B.}
}
@article {2844,
	title = {Protective effects of Lavandula viridis L{\textquoteright}H{\'e}r extracts and rosmarinic acid against H2O2-induced oxidative damage in A172 human astrocyte cell line},
	journal = {Industrial Crops and Products},
	volume = {50},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {361 - 365},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84883032293\&partnerID=40\&md5=cd7f6ece6d2d39d998d9b9a7fa0f5d97},
	author = {Costa, P. and Sarmento, B. and Gon{\c c}alves, S. and Romano, A.}
}
@article {2841,
	title = {Towards the characterization of an in vitro triple co-culture intestine cell model for permeability studies},
	journal = {International Journal of Pharmaceutics},
	volume = {458},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {128 - 134},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84888328477\&partnerID=40\&md5=08a91f0c4957ab3d8d2734e503d5a27c},
	author = {Ara{\'u}jo, F. and Sarmento, B.}
}
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},
	month = {2012///},
	pages = {607 - 621},
	abstract = {In vitro cell models have been used to predict drug permeation in early stages of drug development, since they represent an easy and reproducible method, allowing the tracking of drug absorption rate and mechanism, with an advantageous costbenefit ratio. Such cell-based models are mainly composed of immortalized cells with an intrinsic ability to grow in a monolayer when seeded in permeable supports, maintaining their physiologic characteristics regarding epithelium cell physiology and functionality. Areas covered: This review summarizes the most important intestinal, pulmonary, nasal, vaginal, rectal, ocular and skin cell-based in vitro models for predicting the permeability of drugs. Moreover, the similitude between in vitro cell models and in vivo conditions are discussed, providing evidence that each model may provisionally resemble different drug absorption route. Expert opinion: Despite the widespread use of in vitro cell models for drug permeability and absorption evaluation purposes, a detailed study on the properties of these models and their in vitroin vivo correlation compared with human data are required to further use in order to consider a future drug discovery optimization and clinical development. {\textcopyright} 2012 Informa UK, Ltd.},
	keywords = {Animals, Caco-2 Cells, carcinoma cell, cell differentiation, cell growth, Cell Line, Cell Membrane Permeability, cell models, cell proliferation, cell strain CACO 2, cell type, Cells, conjunctiva, drug absorption, drug bioavailability, drug delivery system, drug penetration, drug screening, drug transport, epithelium cell, Eye, human, Humans, in vitro models, in vitro study, in vitroin vivo correlation, Intestinal Absorption, intestinal mucosa, intestine cell, Intestines, Lung, lung alveolus cell, Models, Biological, molecular weight, nasal cell, nonhuman, ocular cell, permeability, Pharmaceutical Preparations, rectal cell, review, Skin, skin cell, vaginal cell},
	isbn = {17425255 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84859967380\&partnerID=40\&md5=f531a0a6e96c96e8daf71a6b36dbec8a},
	author = {Sarmento, B. and Andrade, F. and Da Silva, S.B. and Rodrigues, F. and Das Neves, J. and Ferreira, D.}
}
@booklet {2185,
	title = {The importance of antimicrobial peptides and their potential for therapeutic use in ophthalmology},
	howpublished = {International Journal of Antimicrobial AgentsInt. J. Antimicrob. Agents},
	year = {2012},
	note = {Export Date: 21 November 2012Source: ScopusArticle in PressCODEN: IAAGEdoi: 10.1016/j.ijantimicag.2012.07.020Language of Original Document: EnglishCorrespondence Address: Pintado, M.; CBQF-College of Biotechnology, Catholic University of Portugal, Rua Dr Ant{\'o}nio Bernardino deemail: mpintado@porto.ucp.pt},
	month = {2012///},
	abstract = {The reduced effectiveness of some of the most important antibiotics owing to increasing resistance of microorganisms as well as the absence of new classes of antimicrobial agents have been concerning researchers and clinicians in recent years. Thus, the development and approval of new compounds for clinical applications is of great importance. Among these compounds, antimicrobial peptides (AMPs) appear to be excellent candidates for the development of novel antimicrobial agents. Some AMPs and antimicrobial proteins have been shown to be active against relevant pathogens in ocular infections as well as in biofilm eradication from contact lenses. Thus, they are considered promising in the prevention and management of ocular diseases. This review summarises the main classes and characteristics of AMPs and antimicrobial proteins, in particular those found in ocular structures and fluids. Some AMPs with activity against ocular pathogens and their potential as therapeutic agents to treat and prevent ocular infections are emphasised. {\textcopyright} 2012.},
	keywords = {Antimicrobial peptide, Antimicrobial protein, Ocular infection, Ophthalmology},
	isbn = {09248579 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84867901653\&partnerID=40\&md5=c1e455bf510a619011a259e85dcb6156},
	author = {Silva, N.C. and Sarmento, B. and Pintado, M.}
}
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},
	month = {2012///},
	pages = {3347 - 3356},
	abstract = {The interaction with cervicovaginal mucus presents the potential to impact the performance of drug nanocarriers. These systems must migrate through this biological fluid in order to deliver their drug payload to the underlying mucosal surface. We studied the ability of dapivirine-loaded polycaprolactone (PCL)-based nanoparticles (NPs) to interact with a simulated vaginal fluid (SVF) incorporating mucin. Different surface modifiers were used to produce NPs with either negative (poloxamer 338 NF and sodium lauryl sulfate) or positive (cetyltrimethylammonium bromide) surface charge. Studies were performed using the mucin particle method, rheological measurements, and real-time multiple particle tracking. Results showed that SVF presented rheological properties similar to those of human cervicovaginal mucus. Analysis of NP transport indicated mild interactions with mucin and low adhesive potential. In general, negatively charged NPs underwent subdiffusive transport in SVF, i.e., hindered as compared to their diffusion in water, but faster than for positively charged NPs. These differences were increased when the pH of SVF was changed from 4.2 to 7.0. Diffusivity was 50- and 172-fold lower in SVF at pH 4.2 than in water for negatively charged and positively charged NPs, respectively. At pH 7.0, this decrease was around 20- and 385-fold, respectively. The estimated times required to cross a layer of SVF were equal to or lower than 1.7 h for negatively charged NPs, while for positively charged NPs these values were equal to or higher than 7 h. Overall, our results suggest that negatively charged PCL NPs may be suitable to be used as carriers in order to deliver dapivirine and potentially other antiretroviral drugs to the cervicovaginal mucosal lining. Also, they further reinforce the importance in characterizing the interactions of nanosystems with mucus fluids or surrogates when considering mucosal drug delivery. {\textcopyright} 2012 American Chemical Society.},
	keywords = {microbicides, mucin, mucoadhesion, mucosal drug delivery, particle tracking, rheology},
	isbn = {15438384 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84868526145\&partnerID=40\&md5=bd161f1b2ce30fba31c7a482dbe60b86},
	author = {Das Neves, J. and Rocha, C.M.R. and Gon{\c c}alves, M.P. and Carrier, R.L. and Amiji, M. and Bahia, M.F. and Sarmento, B.}
}
