Just in Time Dendrimers

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Natural melanin: A potential pH-responsive drug release device

Publication . Araújo, Marco; Viveiros, Raquel; Correia, Tiago R.; Correia, Ilídio Joaquim Sobreira; Bonifácio, Vasco; Casimiro, Teresa; Ricardo, Ana Aguiar

This work proposes melanin as a new nanocarrier for pH-responsive drug release. Melanin is an abundant natural polymer that can be easily extracted from cuttlefish as nanoparticles with a suitable size range for drug delivery. However, despite its high potentiality, the application of this biopolymer in the pharmaceutical and biomedical fields is yet to be explored. Herein, melanin nanoparticles were impregnated with metronidazole, chosen as model antibiotic drug, using supercritical carbon dioxide. The drug release profile was investigated at acidic and physiologic pH, and the dominant mechanism was found to follow a non-Fickian transport. Drug release from melanin shows a strong pH dependency, which allied to its biocompatibility and lack of cytotoxicity envisages its potential application as nanocarrier in formulations for colon and intestine targeted drug delivery.

2014-04-23Journal article

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Biocompatible oligo-oxazoline crosslinkers: Towards advanced chitosans for controlled dug release

Publication . Lopes, Mafalda; Restani, Rita; Carvalho, Marco António Paulo de; Correia, I.J.; Ricardo, Ana Aguiar; Bonifácio, Vasco

Chitosan, a natural and abundant biopolymer has been long explored as a biocompatible material for the preparation of drug delivery devices. This strategy has been mostly accomplished using chemically crosslinked chitosan leading to more stable scaffolds. However, crosslinking has been shown to reduce both biocompatibility and swelling. In this work chitosan was crosslinked with novel biocompatible crosslinkers, based on oligo-oxazolines and glycidyl methacrylate copolymers, leading to patches with a very high swelling capacity. Dexamethasone therapeutics is strongly enhanced by a controlled release administration. This study shows that oligo-oxazoline-crosslinked chitosan is a suitable biomaterial for loading and controlled release of dexamethasone.

2021Journal article

Open access

Biocompatible Polyurea Dendrimers with pH‐Dependent Fluorescence

Publication . Restani, Rita; Morgado, Patrícia I.; Ribeiro, MP.; Correia, I.J.; Ricardo, Ana Aguiar; Bonifácio, Vasco

Biocompatible and biodegradable water‐soluble dendrimers comprising ureas within the interior and amino groups on the periphery were synthesized in supercritical carbon dioxide (dendrimer of generation 1 shown in picture). This novel class of dendrimers shows a pH‐dependent intrinsic blue fluorescence at very low concentrations, which makes them potential polymeric fluorescent cell markers.

2012-04-05Journal article

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Polyurea dendrimer for efficient cytosolic siRNA delivery

Publication . Restani, Rita; Conde, João; Baptista, Pedro; Cidade, Maria Teresa Varanda; Bragança, Ana; Morgado, Jorge; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana Aguiar; Bonifácio, Vasco

The design of small interfering RNA (siRNA) delivery materials showing efficacy in vivo is at the forefront of nanotherapeutics research. Polyurea (PURE-type) dendrimers are ‘smart’ biocompatible 3D polymers that unveil a dynamic and elegant back-folding mechanism involving hydrogen bonding between primary amines at the surface and tertiary amines and ureas at the core. Similarly, to a biological proton pump, they are able to automatically and reversibly transform their conformation in response to pH stimulus. Here, we show that PURE-G4 is a useful gene silencing platform showing no cellular toxicity. As a proof of concept we investigated the PURE-G4-siRNA dendriplex, which was shown to be an attractive platform with high transfection efficacy. The simplicity associated with the complexation of siRNA with polyurea dendrimers makes them a powerful tool for efficient cytosolic siRNA delivery.

2014-10-07Journal article

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