Enhanced pharmacokinetic approach for anastrozole via macromolecule-based silk fibroin nanoparticles incorporated in situ injectables for oestrogen-positive breast cancer therapy

Breast Cancer (BC) is a substantial reason for cancer-related mortality among women across the globe. Anastrozole (ANS) is an effective orally administered hormonal therapy for oestrogen-positive (ER+) BC treatment. However, several side effects and pharmacokinetic limitations restricted the uses of ANS in BC therapy. Therefore, this investigation developed an in situ gelling injectable-loaded silk fibroin (SF)-ANS NPs, which offers sustained drug release and improved pharmacokinetic properties compared to conventional oral formulations at the targeted site. The optimised in situ gel (ISG) incorporated SF-ANS-NPs were developed, and the pharmacokinetic parameters were accessed in subcutaneous administration of NMU-induced Wistar albino rats. The results demonstrated that SF-ANS-NP-ISG exhibited a significantly higher C_max, T_max, and AUC compared to pure ANS suspension. In addition, tumour multiplicity (1.40 ± 0.66), tumour latency (75 ± 9.2 days), and incidence rate (90 ± 2.1%) were recorded, and post-treatment analysis reported a marked reduction in tumour volume and weight compared to positive control within 90 days of a single dose. The SF-ANS-NP-ISG treated group's histopathological assessment indicated a low-grade carcinoma, reduced epithelial hyperplasia, and haemorrhage in mammary tumour tissues compared to positive control. Thus, the SF-ANS-NPs-ISG investigated to overcome the pharmacokinetic limitations of ANS further exhibited targeted delivery and bioavailability compared to conventional dosage forms.

Anastrozole; Biological macromolecules; Breast cancer; In situ gel; Oestrogen receptor; Pharmacodynamics; Pharmacokinetics; Silk fibroin.