Optimizing molecular weight of octyl chitosan as drug carrier for improving tumor therapeutic efficacy

Abstract

Macromolecular drug carriers have attracted much attention taking advantage of passive tumor targeting property and excellent biocompatibility. For many biomedical applications, however, the effectiveness of the carriers is insufficient, which complicate further development into clinical use. Here, we systematically investigated the effects of molecular weight (from 1KDa to 300KDa) of macromolecular drug carrier, octyl chitosan, on tumor accumulation and penetration, as well as drug loading and releasing profiles. It was found that the molecular weight of chitosan influenced the cellular uptake and pharmacokinetic behavior of the nanocarriers, which ultimately determined their drug delivery efficiency. Interestingly, increased molecular weight of chitosan decreased its cellular uptake but increased its resident time in blood, which provided ample time for tumor accumulation. Moreover, the molecular weight altered the drug loading capability and release profile. Our results demonstrated that 10KDa octyl chitosan was an ideal candidate for anticancer drug delivery, which could deliver anticancer agent to tumor tissues and release drugs in tumor cells more effectively than those of other molecular weights, and finally result in better therapeutic effect.

Hyaluronic Acid-Tacrolimus Bioconjugate: Synthesis, Characterization, and Pharmacokinetic Investigation of an Acid-Responsive Macromolecular Prodrug

“…In fact, previous literature indicated that dextran-TAC conjugate was estimated to contain 0.45% of TAC . However, the drug loading in our HA-ADH-TAC conjugate has been increased to 1% approximately, which could be attributed to the low molecular weight of HA used in the study …”

“…26 However, the drug loading in our HA-ADH-TAC conjugate has been increased to 1% approximately, which could be attributed to the low molecular weight of HA used in the study. 46 3.3. Solubility Studies.…”

Kinetics and efficacy of antibody drug conjugates in 3D tumour models

“…Other groups have shown that molecules of low molecular weight, such as DM1 and MMAE, penetrate compact surfaces at much faster rates than large molecules of high molecular weight (32) (37) (38). For instance, Zhang et al, recently showed that if the molecular weight of the molecular drug carrier, octyl chitosan (OC), is 1kDa, it is able to fully penetrate into spheroids after 8 hours of incubation (39). However, if the molecular weight of OC is of 10kDa, its penetration efficiency drops by over 50% after 8h of incubation.…”