Ocular Tolerability and In Vivo Bioavailability of Poly(ethylene glycol) (PEG)‐Coated Polyethyl‐2‐Cyanoacrylate Nanosphere‐Encapsulated Acyclovir

• Published in: Journal of pharmaceutical sciences 2001-03, Vol.90 (3), p.288-297
• Main Authors: Fresta, Massimo, Fontana, Giacomo, Bucolo, Claudio, Cavallaro, Gennara, Giammona, Gaetano, Puglisi, Giovanni
• Format: Article
• Language: English
• Subjects: acyclovir; Acyclovir - administration & dosage; Acyclovir - pharmacokinetics; Acyclovir - pharmacology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Antiviral Agents - pharmacology; Biological and medical sciences; Biological Availability; Cyanoacrylates - chemistry; Drug Carriers; eye; Eye - drug effects; General pharmacology; Male; Medical sciences; Microspheres; nanospheres; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Rabbits; toxicity and bioavailability
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/1520-6017(200103)90:3<288::AID-JPS4>3.0.CO;2-5

Acyclovir‐loaded polyethyl‐2‐cyanoacrylate (PECA) nanospheres were prepared by an emulsion polymerization process in the micellar phase and characterized. The influence of the presence of nonionic surfactant as well as other substances [i.e., 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CyD) and poly(ethylene glycol) (PEG)], on formulation parameters and loading capacity was investigated. In particular, the presence of PEG resulted in an increase of mean size and size distribution. To obtain PEG‐coated PECA nanospheres with a mean size of  1.5% (w/v) should be used during preparation. The presence of PEG also resulted in a change in zeta potential, from −25.9 mV for uncoated nanospheres to −12.2 mV for PEG‐coated PECA nanospheres. The presence of HP‐β‐CyD elicited an increase of nanosphere size and size distribution, but zeta potential was not influenced. In vitro drug release from nanospheres was determined in both phosphate buffer (pH 7.4) and plasma. The presence of HP‐β‐CyD and PEG did not influence the acyclovir release rate in plasma. In the case of release in phosphate buffer, PEG‐coated nanospheres showed a slower release. Ocular tolerability of PEG‐coated PECA nanospheres was evaluated by the in vivo Draize test. This colloidal carrier was well tolerated, eliciting no particular inflammation at the level of the various ocular structures. In vivo ocular bioavailability was evaluated by instilling 50 μL of the acyclovir‐loaded nanospheres only once in the conjunctival sac of rabbit eyes. At various time intervals, aqueous humour acyclovir content was determined by high‐performance liquid chromatography. Acyclovir‐loaded PEG‐coated PECA nanospheres were compared with an aqueous solution of the drug and a physical mixture of acyclovir nanospheres. The acyclovir‐loaded PEG‐coated PECA nanospheres showed a significant (p