Enhanced pharmacokinetic approach for anastrozole via macromolecule-based silk fibroin nanoparticles incorporated in situ injectables for oestrogen-positive breast cancer therapy.
Arfa Nasrine, Sourav Mohanto, Soumya Narayana, Mohammed Gulzar Ahmed
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引用次数: 0
Abstract
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 Cmax, Tmax, 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.
期刊介绍：
Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs.
Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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