Drug Delivery


smallbutton_orangeGROUP LEADER | MAJOR INTERESTS | RESEARCH TEAM | CURRENT PROJECTS | RELEVANT PUBLICATIONS 

drugdelivery

GROUP LEADER
Bruno Sarmento | ORCID

 

MAJOR INTERESTS
Our research interests lay on the study of new drug delivery systems, namely nanoparticles, micelles and therapeutic polymers, and their application in the pharmaceutical, biomedical and functional food fields. We have also interest in study the impact of delivery system properties on the patient compliance. Additionally, we study polymorphisms and applied pharmacogenomics for optimize clinical practice and individualization of treatments.

Specifically we aim at:

  • Develop functionalized nanodelivery systems for diagnostics and treatment in cancer and infection diseases.
  • Propose in vitro cell models as tools to correlate the transport/absorption of drugs across human mucosae and other barriers.
  • Study of the psychosocial variables and technological characteristics that influence adherence to treatment in order to increase the effectiveness of topical anti-psoriatic therapy.
  • Develop new encapsulation processes and formulations to protect and deliver bioactives (probiotics, polyphenols) to target sites in the gastrointestinal tract.
  • Develop and test microencapsulated probiotics microcapsules, in combination with other bioactives, understanding the effect of food matrices on the release of microencapsulated and their impact on colorectal cancer and gut health.
  • Evaluate the impact of polymorphisms and pharmacogenomics on the clinical outcomes, for combined chemotherapy regimens, in cancer and rheumatoid arthritis.

 

RESEARCH TEAM

Researchers
Áurea Lima | aurea.lima@iscsn.cespu.pt | ORCID
Bruno Sarmento | bruno.sarmento@iscsn.cespu.pt | ORCID
Joaquim Monteiro | joaquim.monteiro@iscsn.cespu.pt |ORCID
José C. Andrade | jose.andrade@iscsn.cespu.pt | ORCID
José das Neves | j.dasneves@ineb.up.pt | ORCID
Maribel Teixeira | maribel.teixeira@iscsn.cespu.pt | ORCID
Vitor Seabra | vitor.seabra@iscsn.cespu.pt | ORCID

PhD Students
Ana Costa | ana.margarida.costa@ineb.up.pt | ORCID
Daniella Silva | danyss8@hotmail.com | ORCID
Elisabete Fernandes | elisabetecfernandes@ineb.up.pt | ORCID
Flávia Sousa | flaviac.m.sousa@gmail.com | ORCID
Francisca Araújo | francisca.araujo@ineb.up.pt | ORCID
Pedro Castro | pedro_joao_castro@hotmail.com | ORCID
Pedro Fonte | pedrofonte86@gmail.com | ORCID
Rute Nunes | rute.nunes@ineb.up.pt | ORCID
Vanessa Nascimento | anavanessa65@gmail.com | ORCID

MSc Students
Andreia Almeida | up201107712@fe.up.pt | ORCID
Mónica Francisco Silva | monitasilva_5@hotmail.com |

Volunteers
Cátia Cunha | catia_cunha_95@hotmail.com | ORCID
Inês Ribeiro | ines_ribeiro9@hotmail.com |
Rui Moura | ruipedropiresmoura@hotmail@hotmail.com |ORCID

Research Technician
Nilza Ribeiro | nilza.ribeiro@cespu.pt | ORCID
Virgínia Gonçalves | virginia.goncalves@cespu.pt | ORCID

 

CURRENT PROJECTS

Project ElectrospunnScar-CESPU-2016: Development of biocomposites fibrous scaffolds as topical 5-fluorouracil carriers for inhibiting hypertrophic scar. | PI: Bruno Sarmento | Team: Bruno Sarmento, Hassan Bousbaa, José das Neves, Ana Francisca Araújo, Pedro Castro, Rute Nunes, Flávia Sousa, Wunguo Cui | Funding Entity: CESPU | Period covered: 04-2016 to 03-2017

Hypertrophic scars (HS) are medical complications in the long term of repairing tissue damage. In this project, molecular brush modified mesoporous silica nanoparticles (MSN) containing 5-Fluorouracil (5-FU) will be prepared through free radical initiated polymerization, and electrospun into poly(L-lactic) acid (PLLA) fibers, in collaboration with Guangdong University, China. Long-term 5-FU release mechanism from electrospun composite fibers will be evaluated, as well as the effect of the molecular brush density and length on the drug release. A deep mechanical properties assessment will be performed and adjusted to topical purposes. It will also be established the mechanism of promoting repairing tissue damage in vitro, and confirm biocopatibility of scaffolds in skin cell lines. This research, from the perspective of combining treatment, provides a scientific basis for functional applications of long-term drug carriers of cell growth scaffolds in skin repair. This project joins research teams highly experimented in biomaterials for tissue regeneration (IINFACTS and Guangdong University) and will support a FCT project recently submitted to fund the in vivo studies.


Project Nano2FcRn-CESPU-2016Bioengineered FcRn-targeting nanoparticles for intestinal delivery of biopharmaceuticals. | PI: Bruno Sarmento | Team: Bruno Sarmento, Vítor Seabra, José das Neves, Ana Francisca Araújo, Ana Margarida Costa, Rute Nunes, Flávia Sousa, Andreia Almeida, João Pedro Martins, Hélder Santos, Cátia Cunha, Rui Moura | Funding Entity: CESPU | Period covered: 04-2016 to 03-2017

To maintain patient compliance, oral administration is the preferred drug delivery route. Yet, many drugs do not endure the harsh environment of the gastrointestinal tract and/or poorly cross the intestinal epithelial barrier. Overcoming these hurdles is possible with nanoparticle (NP) encapsulation, but NP transport across the intestinal epithelium is requiring more efficient, oral delivery nanosystems. A strategy for surpassing the intestinal barrier is through exploitation of receptor-mediated transcytosis, and the neonatal Fc receptor (FcRn) holds tremendous promise. Here, we hypothesize that orally-administered PLGA NPs, functionalized with Fc fractions, will enhance their transport across the intestinal epithelium. NPs will be functionalized with synthetic, recombinantly-produced human Fc-derived ligands, following physicochemical and technological characterization. Biological characterization with in vitro mono- and co-culture cell models will measure FcRn-binding efficiency and specificity, cytotoxicity, and permeation efficiency.

 

RELEVANT PUBLICATIONS

Shahbazi M-A, Shrestha N, Mäkilä E, Araújo F, Correia A, Ramos T, Sarmento B, Salonen J, Hirvonen J, Santos HA

.2015

. A prospective cancer chemo-immunotherapy approach mediated by synergistic CD326 targeted porous silicon nanovectors (Journal Article)

Nano Research, 8 pp. 1505-1521.DOI: 10.1007/s12274-014-0635-4.

(BibTeX)

Roy U, Rodríguez J, Barber P, Neves Jd, Sarmento B, Nair M

.2015

. The potential of HIV-1 nanotherapeutics: from in vitro studies to clinical trials. (Journal Article)

Nanomedicine (Lond), .DOI: 10.2217/nnm.15.160.

(BibTeX)

Araujo F, Shrestha N, Shahbazi M-A, Liu D, Herranz-Blanco B, Makila EM, Salonen JJ, Hirvonen JT, Granja PL, Sarmento B, Santos HA

.2015

. Microfluidic Assembly of a Multifunctional Tailorable Composite SysteDesigned for Site Specific Combined Oral Delivery of Peptide Drugs (Journal Article)

9 pp. 8291–8302.DOI: 10.1021/acsnano.5b02762.

(BibTeX)

Shrestha N, Shahbazi M-A, Araújo F, Makila E aR Janne, Kauppinen EI, Salonen J, Sarmento B, Hirvonen J, Santos HA

.2015

. Multistage pH-responsive mucoadhesive nanocarriers prepared by aerosol flow reactor technology: A controlled dual protein-drug delivery system (Journal Article)

Biomaterials, 68 pp. 9-20.DOI: 10.1016/j.biomaterials.2015.07.045.

(BibTeX)

Albuquerque J, Moura CC, Sarmento B, Reis S

.2015

. Solid Lipid Nanoparticles: A Potential Multifunctional Approach towards Rheumatoid Arthritis Theranostics (Journal Article)

molecules, 20 pp. 11103-11118.DOI: 10.3390/molecules200611103.

(BibTeX)

Mendes B, Marques C, Carvalho I, Costa P, Martins S, Ferreira D, Sarmento B

.2015

. Influence of glioma cells on a new co-culture in vitro blood–brain barrier model for characterization and validation of permeability (Journal Article)

490 pp. 94–101.

(BibTeX)

Castro PM, Fonte P, Sousa F, Madureira AR, Sarmento B, Pintado ME

.2015

. Oral films as breakthrough tools for oral delivery of proteins/peptides (Journal Article)

Journal of Controlled Release, 211 pp. 63 –73.DOI: 10.1016/j.jconrel.2015.05.258.

(BibTeX)

Fernandes E, Ferreira JA, Peixoto A, Lima L, Barroso S, Sarmento B, Santos LL

.2015

. New trends in guided nanotherapies for digestive cancers: A systematic review (Journal Article)

209 pp. 288–307.DOI: 10.1016/j.jconrel.2015.05.003.

(BibTeX)

Rodrigues F, Gaspar C, Palmeira-de-Oliveira A, Sarmento B, Helena Amaral M, P P Oliveira MB

.2015

. Application of Coffee Silverskin in cosmetic formulations: physical/antioxidant stability studies and cytotoxicity effects. (Journal Article)

Drug Dev Ind Pharm, pp. 1–8.DOI: 10.3109/03639045.2015.1035279.

(BibTeX)

Soddu E, Rassu G, Giunchedi P, Sarmento B, Gavini E

.2015

. From naturally-occurring neurotoxic agents to CNS shuttles for drug delivery. (Journal Article)

Eur J Pharm Sci, .DOI: 10.1016/j.ejps.2015.04.005.

(BibTeX)

Pereira C, Araújo F, Barrias CC, Granja PL, Sarmento B

.2015

. Dissecting stromal-epithelial interactions in a 3D in vitro cellularized intestinal model for permeability studies (Journal Article)

56 pp. 36 - 45.

(BibTeX)

Gomes MJ, Martins S, Sarmento B

.2015

. siRNA as a tool to improve the treatment of brain diseases: Mechanism, targets and delivery. (Journal Article)

Ageing Res Rev, .DOI: 10.1016/j.arr.2015.03.001.

(BibTeX)

Dores-Sousa JL, Duarte JA, Seabra V, Bastos ML, Carvalho F, Costa VM

.2015

. The age factor for mitoxantrone's cardiotoxicity: Multiple doses render the adult mouse heart more susceptible to injury. (Journal Article)

Toxicology, 329 pp. 106–119.DOI: 10.1016/j.tox.2015.01.006.

(BibTeX)

Andrade F, Fonte P, Oliva M, Videira M, Ferreira D, Sarmento B

.2015

. Solid state formulations composed by amphiphilic polymers for delivery of proteins: characterization and stability. (Journal Article)

Int J Pharm, .DOI: 10.1016/j.ijpharm.2015.03.050.

(BibTeX)

Fonte P, Araújo F, Silva C, Pereira C, Reis S, Santos HA, Sarmento B

.2015

. Polymer-based nanoparticles for oral insulin delivery: Revisited approaches. (Journal Article)

Biotechnol Adv, .DOI: 10.1016/j.biotechadv.2015.02.010.

(BibTeX)

das Neves J, Sarmento B

.2015

. Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides. (Journal Article)

Acta Biomater, .DOI: 10.1016/j.actbio.2015.02.007.

(BibTeX)

Sousa F, Castro P, Fonte P, Sarmento B

.2015

. How to overcome the limitations of current insulin administration with new non-invasive delivery systems. (Journal Article)

Ther Deliv, 6 (1), pp. 83–94.DOI: 10.4155/tde.14.82.

(BibTeX)

Ara'ujo F, Pereira C, Costa J, Barrias C, Granja PL, Sarmento B

.2015

. In vitro M-like cells genesis through a tissue-engineered triple-culture intestinal model (Journal Article)

Journal of Biomedical Materials Research Part B: Applied Biomaterials, .DOI: 10.1002/jbm.b.33508.

(BibTeX)

Marslin G, Selvakesavan RK, Franklin G, Sarmento B, Dias AC

.2015

. Antimicrobial activity of cream incorporated with silver nanoparticles biosynthesized from Withania somnifera. (Journal Article)

Int J Nanomedicine, 10 pp. 5955–5963.DOI: 10.2147/IJN.S81271.

(BibTeX)

Lopes MA, Abrahim-Vieira B'a, Oliveira C, Fonte P, Souza AM, Lira T, Sequeira JA, Rodrigues CR, Cabral L'uM, Sarmento B, others

.2015

. Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation (Journal Article)

International journal of nanomedicine, 10 pp. 5865.DOI: 10.2147/IJN.S86313.

(BibTeX)

Andrade F, das Neves J'e, Gener P, Schwartz S'o, Ferreira D, Oliva M, Sarmento B

.2015

. Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin (Journal Article)

Nanomedicine: Nanotechnology, Biology and Medicine, 11 (7), pp. 1621–1631.DOI: 10.1016/j.nano.2015.05.006.

(BibTeX)

das Neves J, Nunes R, Machado A, Sarmento B

.2014

. Polymer-based nanocarriers for vaginal drug delivery. (Journal Article)

Adv Drug Deliv Rev, .DOI: 10.1016/j.addr.2014.12.004.

(BibTeX)

Costa A, Sarmento B, Seabra V

.2014

. Targeted Drug Delivery Systems for Lung Macrophages. (Journal Article)

Curr Drug Targets, .

(BibTeX)

Nunes R, Sarmento B, das Neves J

.2014

. Formulation and delivery of anti-HIV rectal microbicides: advances and challenges. (Journal Article)

J Control Release, 194 pp. 278–294.DOI: 10.1016/j.jconrel.2014.09.013.

(BibTeX)

Lima A, Bernardes M, Azevedo R, Monteiro J, Sousa H, Medeiros R, Seabra V

.2014

. SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients. (Journal Article)

Toxicol Sci, 142 (1), pp. 196–209.DOI: 10.1093/toxsci/kfu162.

(BibTeX)

Araújo F, Shrestha N, Shahbazi M-A, Fonte P, Mäkilä EM, Salonen JJ, Hirvonen JT, Granja PL, Santos HA, Sarmento B

.2014

. The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium. (Journal Article)

Biomaterials, 35 (33), pp. 9199–9207.DOI: 10.1016/j.biomaterials.2014.07.026.

(BibTeX)

Nascimento AV, Singh A, Bousbaa H, Ferreira D, Sarmento B, Amiji MM

.2014

. Mad2 checkpoint gene silencing using epidermal growth factor receptor-targeted chitosan nanoparticles in non-small cell lung cancer model. (Journal Article)

Mol Pharm, 11 (10), pp. 3515–3527.DOI: 10.1021/mp5002894.

(BibTeX)

Lopes D, Nunes C, Martins MCL, Sarmento B, Reis S

.2014

. Eradication of Helicobacter pylori: Past, present and future. (Journal Article)

J Control Release, 189 pp. 169–186.DOI: 10.1016/j.jconrel.2014.06.020.

(BibTeX)

Maya S, Sarmento B, Lakshmanan V-K, Menon D, Seabra V, Jayakumar R

.2014

. Chitosan cross-linked docetaxel loaded EGF receptor targeted nanoparticles for lung cancer cells. (Journal Article)

Int J Biol Macromol, 69 pp. 532–541.DOI: 10.1016/j.ijbiomac.2014.06.009.

(BibTeX)

Shrestha N, Shahbazi M-A, Araújo F, Zhang H, Mäkilä EM, Kauppila J, Sarmento B, Salonen JJ, Hirvonen JT, Santos HA

.2014

. Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers. (Journal Article)

Biomaterials, 35 (25), pp. 7172–7179.DOI: 10.1016/j.biomaterials.2014.04.104.

(BibTeX)

das Neves J, Araújo F, Andrade F, Amiji M, Bahia MF, Sarmento B

.2014

. Biodistribution and pharmacokinetics of dapivirine-loaded nanoparticles after vaginal delivery in mice. (Journal Article)

Pharm Res, 31 (7), pp. 1834–1845.DOI: 10.1007/s11095-013-1287-x.

(BibTeX)

Lima A, Bernardes M, Sousa H, Azevedo R, Costa L, Ventura F, Seabra V, Medeiros R

.2014

. SLC19A1 80G allele as a biomarker of methotrexate-related gastrointestinal toxicity in Portuguese rheumatoid arthritis patients. (Journal Article)

Pharmacogenomics, 15 (6), pp. 807–820.DOI: 10.2217/pgs.13.244.

(BibTeX)

Costa A, Sarmento B, Seabra V

.2014

. An evaluation of the latest in vitro tools for drug metabolism studies. (Journal Article)

Expert Opin Drug Metab Toxicol, 10 (1), pp. 103–119.DOI: 10.1517/17425255.2014.857402.

(BibTeX)

Moura CC, Segundo MA, Neves Jd, Reis S, Sarmento B

.2014

. Co-association of methotrexate and SPIONs into anti-CD64 antibody-conjugated PLGA nanoparticles for theranostic application. (Journal Article)

Int J Nanomedicine, 9 pp. 4911–4922.DOI: 10.2147/IJN.S68440.

(BibTeX)

Lima A, Sousa H, Monteiro J, Azevedo R, Medeiros R, Seabra V

.2014

. Genetic polymorphisms in low-dose methotrexate transporters: current relevance as methotrexate therapeutic outcome biomarkers. (Journal Article)

Pharmacogenomics, 15 (12), pp. 1611–1635.DOI: 10.2217/pgs.14.116.

(BibTeX)

Lima A, Seabra V, Bernardes M, Azevedo R, Sousa H, Medeiros R

.2014

. Role of key TYMS polymorphisms on methotrexate therapeutic outcome in portuguese rheumatoid arthritis patients. (Journal Article)

PLoS One, 9 (10), pp. e108165.DOI: 10.1371/journal.pone.0108165.

(BibTeX)

Lima A, Monteiro J, Bernardes M, Sousa H, Azevedo R, Seabra V, Medeiros R

.2014

. Prediction of methotrexate clinical response in Portuguese rheumatoid arthritis patients: implication of MTHFR rs1801133 and ATIC rs4673993 polymorphisms. (Journal Article)

Biomed Res Int, 2014 pp. 368681.DOI: 10.1155/2014/368681.

(BibTeX)

Gomes MJ, Neves Jd, Sarmento B

.2014

. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system. (Journal Article)

Int J Nanomedicine, 9 pp. 1757–1769.DOI: 10.2147/IJN.S45886.

(BibTeX)

Araújo F, Sarmento B

.2013

. Towards the characterization of an in vitro triple co-culture intestine cell model for permeability studies. (Journal Article)

Int J Pharm, 458 (1), pp. 128–134.DOI: 10.1016/j.ijpharm.2013.10.003.

(BibTeX)

Andrade F, Rafael D, Videira M, Ferreira D, Sosnik A, Sarmento B

.2013

. Nanotechnology and pulmonary delivery to overcome resistance in infectious diseases. (Journal Article)

Adv Drug Deliv Rev, 65 (13-14), pp. 1816–1827.DOI: 10.1016/j.addr.2013.07.020.

(BibTeX)

Soares S, Fonte P, Costa A, Andrade J, Seabra V, Ferreira D, Reis S, Sarmento B

.2013

. Effect of freeze-drying, cryoprotectants and storage conditions on the stability of secondary structure of insulin-loaded solid lipid nanoparticles. (Journal Article)

Int J Pharm, 456 (2), pp. 370–381.DOI: 10.1016/j.ijpharm.2013.08.076.

(BibTeX)

das Neves J, Amiji M, Bahia MF, Sarmento B

.2013

. Assessing the physical-chemical properties and stability of dapivirine-loaded polymeric nanoparticles. (Journal Article)

Int J Pharm, 456 (2), pp. 307–314.DOI: 10.1016/j.ijpharm.2013.08.049.

(BibTeX)

Paiva AM, Pinto RA, Teixeira M, Barbosa CM, Lima RT, Vasconcelos MH, Sousa E, Pinto M

.2013

. Development of noncytotoxic PLGA nanoparticles to improve the effect of a new inhibitor of p53-MDM2 interaction. (Journal Article)

Int J Pharm, 454 (1), pp. 394–402.DOI: 10.1016/j.ijpharm.2013.07.017.

(BibTeX)

Lima A, Azevedo R, Sousa H, Seabra V, Medeiros R

.2013

. Current approaches for TYMS polymorphisms and their importance in molecular epidemiology and pharmacogenetics. (Journal Article)

Pharmacogenomics, 14 (11), pp. 1337–1351.DOI: 10.2217/pgs.13.118.

(BibTeX)

Rodrigues CF, Ascenção K, Silva FAM, Sarmento B, Oliveira MBPP, Andrade JC

.2013

. Drug-delivery systems of green tea catechins for improved stability and bioavailability. (Journal Article)

Curr Med Chem, 20 (37), pp. 4744–4757.

(BibTeX)

Fonte P, Araújo F, Reis S, Sarmento B

.2013

. Oral insulin delivery: how far are we? (Journal Article)

J Diabetes Sci Technol, 7 (2), pp. 520–531.

(BibTeX)

Soares S, Costa A, Sarmento B

.2012

. Novel non-invasive methods of insulin delivery. (Journal Article)

Expert Opin Drug Deliv, 9 (12), pp. 1539–1558.DOI: 10.1517/17425247.2012.737779.

(BibTeX)

Araújo F, Fonte P, Santos HA, Sarmento B

.2012

. Oral delivery of glucagon-like peptide-1 and analogs: alternatives for diabetes control? (Journal Article)

J Diabetes Sci Technol, 6 (6), pp. 1486–1497.

(BibTeX)

Fonte P, Soares S, Costa A, Andrade JC, Seabra V, Reis S, Sarmento B

.2012

. Effect of cryoprotectants on the porosity and stability of insulin-loaded PLGA nanoparticles after freeze-drying. (Journal Article)

Biomatter, 2 (4), pp. 329–339.DOI: 10.4161/biom.23246.

(BibTeX)