With the advancement of technology, drug delivery systems and molecules with more complex architecture are developed. As a result, the drug absorption and disposition processes after administration of these drug delivery systems and engineered molecules become exceedingly complex. As the pharmacokinetic and pharmacodynamic (PK-PD) modeling allows for the separation of the drug-, carrier-and pharmacological systemspecific parameters, it has been widely used to improve understanding of the in vivo behavior of these complex delivery systems and help their development. In this review, we summarized the basic PK-PD modeling theory in drug delivery and demonstrated how it had been applied to help the development of new delivery systems and modified large molecules. The linkage between PK and PD was highlighted. In particular, we exemplified the application of PK-PD modeling in the development of extended-release formulations, liposomal drugs, modified proteins, and antibody-drug conjugates. Furthermore, the model-based simulation using primary PD models for direct and indirect PD responses was conducted to explain the assertion of hypothetical minimal effective concentration or threshold in the exposure-response relationship of many drugs and its misconception. The limitations and challenges of the mechanism-based PK-PD model were also discussed.
For cancer therapy, the usefulness of mesoporous silica nanoparticles (MPSNPs) has been widely discussed, likely due to its inorganic nature and excellent structural features. The MPSNPs‐based chemotherapeutics have been promisingly delivered to their target sites that help to minimize side effects and improve therapeutic effectiveness. A wide array of studies have been conducted to functionalize drug‐loaded MPSNPs using targeting ligands and stimuli‐sensitive substances. In addition, anticancer drugs have been precisely delivered to their target sites using MPSNPs, which respond to multi‐stimuli. Furthermore, MPSNPs have been extensively tested for their safety and compatibility. The toxicity level of MPSNPs is substantially lower as compared to that of colloidal silica; however, in oxidative stress, they exhibit cytotoxic features. The biocompatibility of MPSNPs can be improved by modifying their surfaces. This article describes the production procedures, functionalization, and applications of biocompatible MPSNPs in drug delivery.
Specific and effective delivery of DNA vaccines into dendritic cells (DCs) to express antigens is a precondition for induction of immune responses. Construction of a new DNA vaccine delivery system with the ability of programmed gene transfection may achieve this objective. In this study, we successfully integrated dendritic lipopeptide, charge-reversible polymer, and APC-targeted material into DNA vaccine delivery system through layer-by-layer (LBL) assembly. By the means of adjusting the weight ratios and concentration ratios of components, stable complexes were formulated with a particle size of 256.8 ± 10.7 nm and zeta potential of 25.1 ± 2.3 mV. Moreover, this DNA vaccine delivery system could achieve specific delivery into DCs, high transfection efficiency and low cytotoxicity, holding great promise for immunotherapy.
Surgery is considered to be the favored approach for the treatment of most of the solid tumor malignancies. The quality of life among cancer patients has significantly improved due to...
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