Table 3.
Formulations for overcoming DOX resistance in the preclinical stage.
| Carrier–Type | Formulation and Route of Administration | Experimental Model | Findings | References |
|---|---|---|---|---|
| PLs | PL incorporating DOX, ICG, and P-gp inhibitor quinine (ICG + PLDQ), IV | HT-29 MDR1 positive xenograft mice | P-gp inhibition in tumor cells Increased cellular uptake of DOX and reduction in tumor volume by 25% Increase in survival rate by 2-fold |
[88] |
| Liposomes | DOX-loaded apolipoprotein A1-modified cationic liposome (ApoA1-LipDOX), IV | 4T1 tumor-bearing mice | P-gp inhibition in tumor cells with 3-fold higher DOX concentration in tumor tissue Decrease in tumor volume by 3-fold |
[92] |
| DOX and palmitoyl ascorbate (PA)-loaded liposome (DOX-PA-liposome), IV |
MCF-7 cells | P-gp inhibition in tumor cells Increased DOX uptake in MCF-7 cells by 2.5-fold |
[102] | |
| SD rats | Elevation in DOX AUC by 10-fold compared with DOX–liposome AUC | |||
| MCF-7 breast cancer bearing mice | Tumor size decreased by 2-fold compared with DOX–liposome | |||
| DOX and NaHCO3-loaded HSPC-m2000PEG DSPE–liposome, IV |
4T1 breast cancer-bearing mouse | Increase in DOX concentration by 2–3-fold The average extracellular pH in tumor tissue increased to 7.38 |
[109] | |
| NaHCO3-loaded liposome and Doxil combination, IV | colon26 tumor-bearing mouse | Decrease in tumor size by 9- and 2-fold compared with free DOX and Doxil, respectively | [111] | |
| PMs | DOX-loaded Pluronic F127 micelles with pH-sensitive poly(acrylic acid) at two terminals (PAA-PF127-PAA-PM), IV |
Walker 256 carcinosarcoma-bearing mice | A 3-fold faster DOX release at pH 5.0 than at pH7.4 A 3-fold higher apoptosis rate compared with free DOX |
[104] |
| PNPs | PEG-iPUTDN + NIR exposure, IP | H69AR lung cancer-bearing mice | Bypassed the P-gp-mediated efflux TPP-conjugated DOX was efficiently accumulated in mitochondria Tumor volume and weight decreased by 10-fold |
[95] |
| MSNs | GOD@SiO2-Arg and DOX-MSN hydrogels, SC |
MCF-7/ADR cells | Arg generated NO in the presence of H2O2 and decreased P-gp expression. Low pH facilitated DOX release from DOX–MSN and increased its therapeutic efficacy |
[103] |
| MCF-7/ADR xenograft mice | Tumor volume reduced significantly by 8-fold without causing significant histological abnormalities Survival rate increased by 2-fold |
PL: PEGylated liposome; PMs: polymeric micelles; PNPs: Polymeric nanoparticles; IV: intravenous injection; IP: intraperitoneal injection; SC: subcutaneous injection; ICG: indocyanine green; GOD@SiO2-Arg: glucose oxidase loaded silica nanoparticle with disulfide bonds in the shell and arginine on the surface; DOX-MSN: DOX loaded mesoporous nanosilicate; TPP: triphenylphosphonium; AUC: area under the curve.