Potential use of cholecalciferol polyethylene glycol succinate as a novel pharmaceutical additive

Abstract

D-alpha-tocopheryl polyethylene glycol succinate (TPGS) has been utilized in numerous drug delivery formulations in recent years. Because of its amphiphilic structure, it can be used as emulsifier and vehicle for lipid-based drug delivery formulations. It is also an effective P-glycoprotein (P-gp) inhibitor. However, TPGS represents only one of the surfactants in the class of "Vitamin-PEG" conjugated surfactants. To design a new adjuvant or additive, a conjugate made of vitamin D (cholecalciferol) and PEG-cholecalciferol polyethylene glycol succinate (CPGS) was synthesized via a two-step reaction. We hypothesized that CPGS may exhibit similar characteristics to TPGS, and thus the physicochemical properties as well as the anticancer properties of CPGS were studied. The results demonstrated that CPGS reduced the particle size and increased the encapsulation efficiency of the PLGA nanoparticles, indicating that CPGS may also have the emulsifier function similar to TPGS. The drug release profiles showed that the nanoparticles with CPGS additive had a lower initial burst and more sustained release pattern. In vitro testing with Caco-2 cells showed that CPGS could increase the cytotoxicity of DOX-loaded PLGA nanoparticles. Based on the rhodamine accumulation study, the increased cytotoxicity is possibly due to the P-gp inhibition by CPGS. From current results, the use of CPGS as an adjuvant is promising and may enhance the efficacy of the overall drug delivery system.

Cholecalciferol-PEG Conjugate Based Nanomicelles of Doxorubicin for Treatment of Triple-Negative Breast Cancer

“…TPGS has been reported to inhibit P-gp-mediated drug resistance in MDR1 cDNA-transfected cells (G185) having 27–135-fold more resistance to cytotoxic drugs, thereby increasing cytotoxicity of DOX as compared to parental cells. In another study, cholecalciferol succinate has been reported to block P-gp and enhance accumulation of DOX ( p < 0.05) (28,49). …”

“…Zhao et al used cholecalciferol–PEG succinate as an adjuvant in DOX-loaded PLGA nanoparticles and demonstrated its P-glycoprotein (P-gp) inhibitory potential (28). It has been reported that carboxylesterases present in tumor cells can efficiently convert various prodrugs into their active metabolites (43).…”

“…The critical aggregation concentration (CAC) of PEGCCF micelles was determined by fluorescence spectroscopy using pyrene as a hydrophobic probe according to a procedure reported earlier (28) with slight modifications. Briefly, about 20 μL of a stock solution of pyrene (0.1 mM) in acetone was taken in different glass vials and the solvent was removed by blowing air.…”

“…Despite all these reports, there has been a very limited effort towards the development of a drug delivery carrier with vitamin D with an aim of simultaneously delivering the payload chemotherapeutic. There has been only one report where PEG–vitamin D succinate conjugate was used as a pharmaceutical additive and has been shown to elicit P-gp inhibitory effect on Caco-2 cells (28). Thus, in the present study, we aim to synthesize vitamin D conjugated with PEG (PEGCCF) and explore its dual role of DOX-loaded PEGCCF (PEGCCF-DOX) micelles, i.e.…”

Enzyme immunoassay of vitamin d3 metabolites

“…Выделили 60 мг (48 %) гемисукцината витамина D 3 . ЯМР спектр соответствует описанному в литературе [12]. Иммунизация.…”