Drug Delivery and Translational Research

, Volume 8, Issue 3, pp 461–472 | Cite as

Freeze-dried matrices for ocular administration of bevacizumab: a comparison between subconjunctival and intravitreal administration in rabbits

  • Susi Burgalassi
  • Daniela Monti
  • Nadia Nicosia
  • Silvia Tampucci
  • Eleonora Terreni
  • Andrea Vento
  • Patrizia Chetoni
Original Article


This work was aimed to tune solid matrices for bevacizumab (BVZ) subconjunctival or intravitreal administration in order to prolong drug release, to reduce the number of applications and consequently the side effects. Matrices, with sizes suitable for intravitreal or subconjunctival administration, based on hydroxypropylmethyl cellulose (HPMC), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and polyacrylic acid (PAA) were obtained by freeze-drying of polymeric dispersions either in phosphate buffer solution or water and were sterilized by gamma rays. The matrices were characterized from the technological point of view and evaluated for in vitro release of dextran and BVZ. In vivo evaluation of BVZ release in ocular humours was finally carried out on rabbits. The obtained matrices showed solvent sorption time ranging from a few seconds for PAA to 46 min for HPMC, with shorter times when prepared in buffer solution. The hydration times were up to 5.5-fold higher after sterilization. HPMC and PVA matrices showed a slowdown of the release rate of both dextran and BVZ, but HPMC was selected for following in vivo studies also in consideration of its higher viscosity after rehydration of the matrix. HPMC matrix was well tolerated by the rabbit eye when intravitreally and subconjunctivally administered. The different treatment produced the same effect in terms of drug concentration in aqueous and vitreous humour up to 12 weeks after administration. The results of this study support the possible use of lyophilized matrices as a BVZ delivery system to the posterior segment of the eye.


Bevacizumab Subconjunctival Intravitreal Rabbit Freeze-drying Matrices 



This work was funded by University of Pisa (grant PRA 2016_27). The authors would like to thank Dr. Carla Lenzi and Prof. Giancarlo De Montis for technical support to histological analysis and the relevant interpretation of the results.

Compliance with ethical standards

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  1. 1.Department of PharmacyUniversity of PisaPisaItaly
  2. 2.Cosmofarma srlCasalguidiItaly
  3. 3.Ophthalmology Unit, Versilia Hospital, Azienda USL Toscana nord ovestViareggioItaly

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