A novel long-acting biodegradable depot formulation of anastrozole for breast cancer therapy

• Published in: Materials Science & Engineering C 2017-06, Vol.75, p.535-544
• Main Authors: Shavi, Gopal Venkatesh, Nayak, Usha Yogendra, Reddy, Meka Sreenivasa, Ginjupalli, Kishore, Deshpande, Praful Balavant, Averineni, Ranjith Kumar, Udupa, Nayanabhirama, Sadhu, Satya Sai, Danilenkoff, Cyril, Raghavendra, Ramesh
• Format: Article
• Language: English
• Subjects: Absorbable Implants; Anastrozole; Animals; Biodegradability; Biodegradable polymers; Biodegradation; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer therapies; Drug delivery systems; Drug Implants - chemistry; Drug Implants - pharmacokinetics; Drug Implants - pharmacology; Encapsulation; Evaporation; Feasibility studies; Female; Formulations; Humans; Intramuscular depot; Lactic Acid - chemistry; Lactic Acid - pharmacokinetics; Lactic Acid - pharmacology; Materials science; Medical treatment; Microspheres; Nitriles - chemistry; Nitriles - pharmacokinetics; Nitriles - pharmacology; Pharmacokinetics; Pharmacology; PLA; PLGA; Polyglycolic Acid - chemistry; Polyglycolic Acid - pharmacokinetics; Polyglycolic Acid - pharmacology; Polylactide-co-glycolide; Rats; Rats, Wistar; Solid state; Studies; Sustained release; Triazoles - chemistry; Triazoles - pharmacokinetics; Triazoles - pharmacology
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2017.02.063

The purpose of the present study was to fabricate PLGA 50:50 and PLA microspheres for controlled delivery of anastrozole. The microspheres were prepared by oil-in-water (o/w) emulsion/solvent evaporation technique and evaluated for particle size and encapsulation. The optimised formulations were studied for solid state characterization, in vitro release and pharmacokinetic studies. The maximum encapsulation efficiency for PLGA 50:50 and PLA microspheres with 40:1 polymer - drug ratio was observed to be 78.4±2.5 and 87.7±2.6%. The solid state characterization confirmed dispersion of drug at the molecular level in the polymeric matrix. Microspheres were spherical in shape with a very smooth surface texture. Drug release was found to be in a sustained fashion, releasing constantly up to 720h (30days) for PLGA and 60days for PLA microspheres. The pharmacokinetic study data revealed that the intramuscular administration of PLA microspheres showed improved pharmacokinetic profile as compared to PLGA microspheres, and therefore this formulation can be considered as the best optimised formulation with sustained exposure of the drug in vivo compared to other microspheres. From experimental results, PLA microspheres demonstrate the feasibility of employing biodegradable depot polymeric microspheres of anastrozole for long-term treatment of breast cancer. [Display omitted] •Biocompatible and biodegradable polymers as carriers for delivery of anastrozole in long-term treatment of breast cancer.•The particle size obtained for microspheres makes it amenable for parenteral applications.•Hydrophobic nature of these biodegradable polymers allows slow diffusion of the drug into release media.•Erosion of polymer matrix is the possible mechanism contributing to the release of the drug.•PLA microspheres of anastrozole illustrated prolonged pharmacokinetic profile.