• bioadhesive ocular inserts
• in vivo evaluation
• platelet lysate
• sericin
• technological characterization

The conventional ocular dosage forms are eye drops and suspensions. These dosage forms are easy to instil but they are also rapidly drained away from pre-corneal area by constant tear flow and lacrimo-nasal drainage. Despite the poor bioavailability the cornea is considered to be a major pathway for ocular penetration of topically applied drugs. Recently, hydrogels, viscous liquid formulations, solid delivery devices (inserts, drug-soaked contact lenses), have been investigated in the attempt to improve the efficacy of ocular medications, applying also the concepts of mucoadhesion.
The ocular inserts offer many advantages over conventional dosage forms, like increased ocular residence, possibility of releasing drugs at a slow and constant rate, accurate dosing, exclusion of preservatives and increased shelf life. Moreover, the use of these devices reduces systemic absorption, which otherwise freely occurs with eye drops; it also ensures better patient compliance due to lower frequency of administration and lower incidence of side effects.
The aims of this study were: a) the preparation of bioadhesive ocular inserts based on natural or synthetic polymers (cellulose derivatives, polyvinyl alcohol, natural gums and polysaccharidic polymers) containing appropriate amount of drugs (levofloxacin), natural extract (arabinogalactan and sericin), blood components (platelet lysate) or protein drugs (bevacizumab). b) The technological characterization of the prepared inserts such as: in vitro mucoadhesion test; in vitro drug release study; contact angle measurements; rheological behaviour; swelling studies. c) An in vivo evaluation on albino rabbits of the best experimental formulations to assess the biological compatibility with the ocular structure and the related therapeutic activity.
The AG, SR and LF matrices were prepared by film casting method using film forming polymers (PVP and PVA), natural bioadhesive polymers (CRGs) and glycerin (GL) as a plasticizer. The prepared ocular insert based on Sericin, as active substance, showed very good mucoadhesive properties, useful for retention on the eye surface, and increased the healing rate of corneal wound in rabbits with respect to untreated lesion.
Ocular inserts of levofloxacin showed good technological properties, demonstrated sustained release of the drug for up to 8 h after in vitro studies, and increasing the availability in cul-de-sac as compared to eye drops of the same drug after in vivo studies on albino rabbits.
Lyophilized ocular matrices were prepared for delivering new active substances such as PL and BVZ, which are thermally unstable. The unloaded matrices showed good technological properties, suitable for an ophthalmic application, good mucoadhesive properties, and good in vivo wound healing properties. The addition of PL to the formulations produced matrices still good for the ocular administration. Both freeze-drying process and polymers employed did not disturb the activity of PL, how confirmed by proliferation test on HCE.
All inserts were well tolerated by the rabbit eye and did not produce any irritation.
BVZ loaded matrices has the potential to provide an effective and time constant drug release, even if the kinetics of inserts must be investigated.