Intravenous nanocrystals: fabrication, solidification, in vivo fate, and applications for cancer therapy

ABSTRACTIntroduction Intravenous nanocrystals (INCs) have shown intrinsic advantages in antitumor applications, particularly their properties of high drug loading, low toxicity, and controllable size. Therefore, it has a very bright application prospect as a drug delivery system.Areas covered The ideal formulation design principles, fabrication, solidification, in vivo fate of INCs, the applications in drug delivery system (DDS) and the novel applications are covered in this review.Expert opinion It is vital to select a suitable formulation and fabrication method to produce a stable and sterile INCs. Besides, the type of stabilizers and physical characteristics can also influence the in vivo fate of INCs, which is worthy of further studying. Based on wide researches about applications of INCs in cancer, biomimetic INCs are concerned increasingly for its favorable compatibility. The output of these studies suggested that INCs-based drug delivery could be a novel strategy for addressing the delivery of the drug that faces solubility, bioavailability, and toxicity problems.KEYWORDS: Nanocrystalsfabricationsolidificationin vivo fateapplication Article highlights For the fabrication of INCs, we have explored the fabrication of INCs in depth and discussed the parameters affecting size and stability of INCs. We also focus on sterile preparation process of intravenous INCs to promote biological safety.To address the instability of liquid INCs, various drying methods are described and parameter settings are illustrated. Suitable routes of administration of INCs were obtained by different drying methods, which promoted the clinical applications and mass production of INCs.Combining the characteristics of INCs and tumor microenvironment, the in vivo fate of different INCs after intravenous injection was comprehensively interpreted.As drug carriers, INCs have been used to improve the solubility of the insoluble drug. Coating INCs with novel materials makes it more stable than normal INCs and has the potential to enhance the controlled release/targeting properties of drugs.Biomimetic INCs shed new light on the cancer chemotherapy by virtue of blood compatibility and circulation stability in the field of drug delivery. In the future, INCs can also be used as carriers for combination therapy in the treatment of cancers.The hybrid NCs provide a powerful technique for drug tracking, which clearly showed that the interactions between INCs and tumor cells.AbbreviationsAlbumin, alb; Apolipoprotein E, ApoE; Blood brain barrier, BBB; Camptothecin, CPT; Cancer cell membranes, CCM; Carfilzomib, CFZ; Critical micelle concentration, CMC; Docetaxel, DTX; Drug delivery systems, DDS; Enhanced permeability and retention effect, EPR; Electro spray drying, ESD; Freeze drying, FD; High-pressure homogenization, HPH; Hyaluronic, HA; Hybrid membranes, HM; Intravenous nanocrystals, INCs; Magnetic heat treatment, MHT; Magnetic nanocrystals, MNCs; Nanocrystals, NCs; Polymer dispersity index, PDI; Polyethylene glycol, PEG; Platelet membranes, PM; Particle size, PS; Paclitaxel, PTX; Red blood cell membranes, RBCM; Reactive oxygen species, ROS; Redispersibility, RDI; Spray drying, SD; Spray freeze drying, SFD; Singlet oxygen, 1O2; D-α-tocopherol polyethylene glycol 1000 succinate, TPGS; Vacuum drum drying, VDD; Zeta potential, ZP; Zinc NCs, ZN-NCs.Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was funded by the Shanghai Sailing Program [21YF1447400] and the Program for Shanghai High-Level Local University Innovation Team [SZY20220315].