Polymeric drug conjugates (PDCs) for cancer therapy have been a hot topic of research for the past three decades. Successful examples of PDC conjugates have demonstrated sustained drug release action with decreased systemic toxicity and enhanced tumor retention effect (EPR) via active as well as a passive targeting mechanisms. Therefore, the PDC approach has now become a keystone of the drug delivery system for cancer and other diseases. In recent years, several PDCs have successfully made up to the clinical trials. The approach aids targeted delivery of the anticancer drugs to the tumor site without disturbing the healthy cells. The selection of the over-expressed receptor and the receptor-ligand plays a vital role in designing the receptor-targeting PDC so that it is able to distinguish between the healthy cell and the tumor cell. Continuous efforts are being made in research and development towards active targeted PDC delivery system to revolutionize the treatment of cancer despite the controversy built due to hetereogeneity in tumor models. This review highlights the chemistry aspects involved in the preparation of PDCs that deal with novel molecular tumor targets and strategies used for development of targeted PDCs for delivering the drug payload via active or passive targeting. Further, it throws light on the challenges faced by targeted PDCs as novel drug delivery systems.
Vibrating mesh nebulizers (VMN) demonstrate improved efficiency for delivery of inhaled aerosol solutions or suspensions as compared to compressor devices. The added advantages of compactness, portability and functioning as noise-free device makes them of incremental value in Home or Ambulatory settings while managing Severe Obstructive airway disease or delivery of maintenance medications in these cases. This further circumvents the need for multiple devices thereby further improving patient compliance and convenience while delivering acute or maintenance formulations including Glycopyrronium (GLY) and Formoterol (FRM)/Budesonide(BUD) nebulizing solution formulations. To further assess the clinical role and feasibility of FRM-BUD formulation delivery kinetics with or without GLY nebulizing solution through VMN and jet nebulizers for In- & outpatient settings, 2 comparative in-vitro lung deposition studies were carried out utilizing Anderson Cascade impactor at 30 L/min; deposited drug concentrations in different stages were suitably collected and estimated by HPLC. Post-hoc analyses with p<0.05 was considered statistically significant for intergroup differences on FRM/BUD and GLY delivered through VMN or Compressor devices. The calculated mean fine particle dose for FRM & BUD delivered by VMN or jet nebulizer showed no statistical difference. However the mean fine particle fraction for BUD delivered by VMN was significantly better compared to jet nebulizer than that for FRM. The Residual volume at 10 mins was significantly higher with jet nebulizer. The optimal APSD for GLY nebulizing solution admixture with FRM/BUD suspension delivered through VMN and Jet nebulizer offers a clinically relevant strategy for High risk COPD cases in Acute or Home settings.
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