Spray-dried PDLLA microspheres containing Carboplatin for veterinary use: in vitro and in vivo studies

The aim of this study was the development of a veterinary
dosage form constituted by injectable biodegradable
microspheres designed for the subcutaneous release of
carboplatin, a chemotherapeutic drug. Poly(D,L-lactide)
(PDLLA) microspheres were prepared by an emulsification/
spray-drying method, using the drug-to-polymer
weight ratios 1:9 and 1:5; blank microspheres (1% w/v)
were prepared as a comparison. Microparticles were characterized
in terms of morphology, encapsulation efficiency,
and in vitro drug release behavior. In vivo tests
were conducted on rats by subcutaneous injection of
microsphere aqueous suspensions. Levels of carboplatin
were evaluated both in the skin and in serum. The microparticles
obtained had a spherical shape; particle size
ranged from 5 to 7 mm, dependent on drug loading. Microspheres
were able to control the in vitro release of the drug:
approximately 90% to 100% of the carboplatin was
released over 30 days. In vivo results showed that the
microspheres were able to release high drug amounts
locally, and sustained serum levels of drug were also
achieved. Based on these results, carboplatin-loaded
PDLLA microspheres may be useful for local delivery of
the antineoplastic drug to the tumor, avoiding tumor recurrence
in small animals, and may decrease the formation of
distant metastases.