Challenges and Advances in Oral Drug Delivery using Lipid-based Nanoparticles Faculty of Pharmacy, University of Porto, Portugal Ana Rute Neves Madrid,

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Presentation transcript:

Challenges and Advances in Oral Drug Delivery using Lipid-based Nanoparticles Faculty of Pharmacy, University of Porto, Portugal Ana Rute Neves Madrid, 8 th March 2016

2 Low water solubility High degradation Poor intestinal absorption Rapid metabolism Oral Administration Wide spectrum of drugs:

3 Drugs and Bioactive compounds Nanocarrier Nanodelivery systems

4 Lipid nanoparticles: SLNsSLNs NLCsNLCs - Solid matrix - Perfect crystals - Solid and liquid lipids - Cavities: -to accommodate drug -to control release Nanodelivery systems Neves, AR; Lúcio, M; Martins, S; Lima, JLFC and Reis, S, Int. J. Nanomed. 2013, 8, 177.

Characterization  Morphology by SEM: Spherical shape perfectly defined and is not visible aggregation and agglomeration of nanoparticles. 5 SLNsNLCs Neves, AR; Lúcio, M; Martins, S; Lima, JLFC and Reis, S, Int. J. Nanomed. 2013, 8, 177.

Characterization  Size, PI and Zeta potential: 6 All values represent the mean ± SD (n=3). Z-Average (nm)Polydispersity IndexZeta Potential (mV) SLNs189.2 ± ± 0.045−30.8 ± 7.3 NLCs172.9 ± ± 0.030−29.6 ± 7.4 < 200 nm~ mV Neves, AR; Lúcio, M; Martins, S; Lima, JLFC and Reis, S, Int. J. Nanomed. 2013, 8, 177.

In vitro release studies 7 Neves, AR; Lúcio, M; Martins, S; Lima, JLFC and Reis, S, Int. J. Nanomed. 2013, 8, 177. SLN NLC A B A A – Stomach, pH=1.2, 37 °C B B – Intestine, pH=7.4, 37 °C  Gastrointestinal conditions

8 Cellular uptake of nanoparticles Alexa Fluor 633-WGA DAPI Neves, AR; Queiroz JF; Lima SAC; Figueiredo F; Fernandes R; Reis S, J. Colloid Interface Sci. 2016, 463, 258.

9 Cellular uptake of nanoparticles  Flow cytometry Data Neves, AR; Queiroz JF; Lima SAC; Figueiredo F; Fernandes R; Reis S, J. Colloid Interface Sci. 2016, 463, 258.

10 Internalization pathways 30% 50% 80% 15% Clathrin-mediated Endocytosis Neves, AR; Queiroz JF; Lima SAC; Figueiredo F; Fernandes R; Reis S, J. Colloid Interface Sci. 2016, 463, 258.

11 Transcytosis routes Paracellular route Propranolol Lucifer yellow Transcelullar route Neves, AR; Queiroz JF; Lima SAC; Figueiredo F; Fernandes R; Reis S, J. Colloid Interface Sci. 2016, 463, 258.

12 Conclusions

13 Acknowledgments Sofia Costa Lima Salette Reis Joana F. Queiroz