4.7 Article

Mucoadhesive PLGA Nanospheres and Nanocapsules for Lactoferrin Controlled Ocular Delivery

Journal

PHARMACEUTICS
Volume 14, Issue 4, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics14040799

Keywords

nanoparticles; PLGA; lactoferrin; topical ophthalmic administration; nanoprecipitation; protein nanocarriers; keratoconus; corneal ecstatic disorder

Funding

  1. Spanish Ministry of Economy and Competitiveness (Instituto de Salud Carlos III) [PI18/00159]
  2. Spanish Ministry of Science, Innovation and Universities [RTI2018-099597-B-100]

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This study describes the preparation and optimization of different PLGA-based nanosystems for the delivery of lactoferrin for ocular diseases. The modified polymeric nanocarriers demonstrated suitable size, uniform distribution, and efficient drug encapsulation. In vitro release studies showed controlled delivery of lactoferrin, and no cytotoxicity was observed. The mucoadhesive properties of the nanoparticles were also confirmed in vitro and in vivo.
Background: the present work describes the preparation, characterization and optimization of eight types of PLGA-based nanosystems (nanospheres and nanocapsules) as innovative mucoadhesive drug delivery systems of lactoferrin, in order to achieve a preclinical consistent base as an alternative pharmacological treatment to different ocular syndromes and diseases. Methods: All different nanoparticles were prepared via two modified nanoprecipitation techniques, using a three-component mixture of drug/polymer/surfactant (Lf/PLGA/Poloxamer), as a way to overcome the inherent limitations of conventional PLGA NPs. These modified polymeric nanocarriers, intended for topical ophthalmic administration, were subjected to in vitro characterization, surface modification and in vitro and in vivo assessments. Results: An appropriate size range, uniform size distribution and negative zeta potential values were obtained for all types of formulations. Lactoferrin could be effectively included into all types of nanoparticles with appropriate encapsulation efficiency and loading capacity values. A greater, extended, and controlled delivery of Lf from the polymeric matrix was observed through the in vitro release studies. No instability or cytotoxicity was proved for all the formulations by means of organotypic models. Additionally, mucoadhesive in vitro and in vivo experiments show a significant increase in the residence time of the nanoparticles in the eye surface. Conclusions: all types of prepared PLGA nanoparticles might be a potential alternative for the topical ophthalmic administration of lactoferrin.

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