Preparation of Well-Dispersed Chitosan/Alginate Hollow Multilayered Microcapsules for Enhanced Cellular Internalization

resumo

Hollow multilayered capsules have shown massive potential for being used in the biomedical and biotechnology fields, in applications such as cellular internalization, intracellular trafficking, drug delivery, or tissue engineering. In particular, hollow microcapsules, developed by resorting to porous calcium carbonate sacrificial templates, natural-origin building blocks and the prominent Layer-by-Layer (LbL) technology, have attracted increasing attention owing to their key features. However, these microcapsules revealed a great tendency to aggregate, which represents a major hurdle when aiming for cellular internalization and intracellular therapeutics delivery. Herein, we report the preparation of well-dispersed polysaccharide-based hollow multilayered microcapsules by combining the LbL technique with an optimized purification process. Cationic chitosan (CHT) and anionic alginate (ALG) were chosen as the marine origin polysaccharides due to their biocompatibility and structural similarity to the extracellular matrices of living tissues. Moreover, the inexpensive and highly versatile LbL technology was used to fabricate core-shell microparticles and hollow multilayered microcapsules, with precise control over their composition and physicochemical properties, by repeating the alternate deposition of both materials. The microcapsules' synthesis procedure was optimized to extensively reduce their natural aggregation tendency, as shown by the morphological analysis monitored by advanced microscopy techniques. The well-dispersed microcapsules showed an enhanced uptake by fibroblasts, opening new perspectives for cellular internalization.

palavras-chave

POROUS CACO3 MICROPARTICLES; DRUG-DELIVERY; BIOMEDICAL APPLICATIONS; CALCIUM-CARBONATE; POLYELECTROLYTE MICROCAPSULES; PROTEIN ENCAPSULATION; POLYMER CAPSULES; PARTICLE UPTAKE; CELLS; SHELLS

categoria

Biochemistry & Molecular Biology; Chemistry

autores

Ribeiro, C; Borges, J; Costa, AMS; Gaspar, VM; Bermudez, VD; Mano, JF

Grupos

G4 - Materiais Renováveis e Economia Circular
G5 - Materiais Biomiméticos, Biológicos e Vivos

Projectos

CICECO - Aveiro Institute of Materials (UID/CTM/50011/2013)

Marine Origin Biopolymers as Innovative Building Blocks from the Sea for the Development of Bioresorbable Multilayered Membranes for guided bone regeneration (BLUETEETH)

agradecimentos

The authors acknowledge the financial support by the Portuguese Foundation for Science and Technology (FCT) through the Post-doctoral (SFRH/BPD/103604/2014-Joao Borges; SFRH/BPD/119983/2016-Vitor M. Gaspar) and PhD (SFRH/BD/101748/2014-Ana M. S. Costa) grants. This work was developed within the scope of the project CICECO Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. The work was also supported by the Marine Biotechnology ERA-NET project "BLUETEETH" (ERA-MBT/0002/2015) funded under the EU FP7, as well as by the European Research Council grant agreement ERC-2014-ADG-669858 for the project "ATLAS" funded under Horizon 2020.