Prodrug approaches for the development of a long-acting drug delivery systems

Recent advances in engineering prodrug-based nanomedicines for cancer therapy

“…For all these reasons, developing nanoplatforms that accomplish improved physicochemical properties, prolonged systemic circulation, controlled drug release, and lessened drug toxicity is critically required. 11,12…”

Extended Pharmacokinetics Improve Site-Specific Prodrug Activation Using Radiation

“…In this work, we hypothesized that the in vivo efficiency of radiation-activated prodrugs could be vastly improved through the design of a long-circulating construct that steadily accumulates in tumor tissue and releases chemotherapy payloads following clinically relevant doses or serial dose fractions of RT. Numerous strategies can extend the circulating pharmacokinetics of drug payloads and improve their delivery and retention at tumor sites, − including through payload incorporation into long-circulating PEGylated nanoparticles, , tumor-targeted antibodies, − and serum albumin. − We show how our modular chemical design for radiation-activated prodrugs can apply to each of these strategies and focus especially on serum albumin for its extended blood half-life (3 weeks in humans), relatively low molecular weight and high diffusivity compared to antibodies and nanoparticles, its extensive use in developing both molecularly targeted and passively accumulating therapies for cancer, and its ability to be taken up into tumors via oncogene-driven macropinocytosis and the “enhanced permeability and retention” (EPR) effect. , Thus, we present the design, synthesis, computational PK/PD modeling, and in vivo evaluation of the R adioactivated A lbumin- B ound i nducible T herapeutic (RABiT) platform and show how it efficiently accumulates in tumor tissue, selectively releases drug payload, and synergistically blocks tumor growth in mice.…”

Camptothecin-based prodrug nanomedicines for cancer therapy

“…28 More importantly, nanomedicines could considerably improve the tumor-targeting ability of the drugs via the enhanced permeability and retention (EPR) effect. 29–31 Because of the abovementioned advantages of nanomedicines, CPT has been designed within various nanoprodrugs for the fabrication of prodrug nanomedicines with high tumor uptake and enhanced cancer therapy ability. This review summarizes recent studies of CPT-based nanoprodrugs for the treatment of cancer, focusing on smart CPT nanoprodrugs with stimuli-responsive CPT release ability under tumor-specific microenvironment conditions.…”