Table 4.
DOX formulations to increase oral BA.
| Carrier–Type | Formulation & Route of Administration | Experimental Model | Findings | References |
|---|---|---|---|---|
| PMs | Linolenic acid–chitosan-based PMs (DOX-CS-LA), PO | SD rat | Mucoadhesive formulation Targeting the intestinal fatty acid transporter Increase in relative BA by 166% compared with that of free DOX |
[152] |
| Lysine-linked ditocopherol polyethylene glycol 2000 succinate (PLV2K-DOX), PO |
SD rat | Intestinal permeability of PLV2K–DOX was 3.19-, 1.61-, and 1.80-fold higher than that of free DOX in the duodenum, jejunum, and ileum Orally administered PLV2K–DOX showed 5.6-fold higher AUC than free DOX in rats |
[153,154] | |
| Oleanolic acid conjugated methoxy-poly (ethylene glycol)-poly (D, L-lactide) (mPEG-PLA-OA), PO |
Wistar rats | A 30-fold increased DOX circulation time and 30-fold reduced clearance time | [155] | |
| PNPs | DOX-loaded poly (lactic-co-glycolic acid) (PLGA) NPs, PO |
SD rats | BA enhancement by 363% and reduced cardiotoxicity | [165] |
| Breast cancer bearing rats | Reduced tumor size, increased survival rate, and reduced cardiotoxicity | |||
| Chitosan coated–daunorubicin PLGA–NPs, PO | Wistar rats | Compared with free daunorubicin, a 11.3-fold higher AUC and 2.8-fold delay in the elimination of daunorubicin from the plasma | [168] | |
| PEGylated-DOX-loaded-PLGA–NPs, PO | Wistar rats | Compared with free DOX, a 11.8-fold higher AUC and 2.1-fold delay in the elimination of DOX from the plasma | [167] | |
| Chitosan modified chitosan diacetate (CDA) and chitosan triacetate (CTA)-NPs, PO | MCF-7 cells | Approximately 2-fold increased permeability of DOX in MCF-7 cells | [169] | |
| SD rats | Compared with free DOX, sustained release for 24 h, and 3-fold increase in the AUC of DOX–CTA NPs |
|||
| Intestine-penetrating, pH-sensitive and double layered NPs, PO |
H22-tumor bearing mice | Relative BA of 75.4% with effective inhibition of tumor growth DOX concentrations in major tissues did not exceed the maximum tolerated concentration Approximately 40% of the absorbed DOX accumulated in the tumor tissue |
[170] | |
| Sodium caseinate (NaCN) NPs, PO | 4T1-breast cancer bearing mice | A 8-fold tumor shrinkage compared with that of free DOX Following the oral administration of DOX–NaCN NPs, DOX in tumor tissues showed 8.34-fold higher accumulation than IV DOX and 1.27-fold higher accumulation than IV DOX–NaCN NPs |
[172] | |
| MMS | Mutilayer alginate beads with codelivery of chitosan-DOX nanogel and quercetin (DOX:CS/CMCS-NGs /Qu-M-ALG-Beads), PO |
SD rats | pH-sensitive release at pH > 7.0. Chitosan increased DOX absorption via mucoadhesion and tight-junction opening Quercetin increased DOX absorption by inhibiting P-gp. BA of DOX:CS /CMCS-NGs/Qu-M-ALG-beads was 55.8% |
[173] |
| MSNs | DOX loaded MSN (DOX-MSN), PO |
SD rats | DOX–MSN with a rod shape and size of 200 nm showed 5.9-fold enhancement in relative BA compared with free DOX | [175] |
PM: Polymeric micelle; PNP: Polymeric nanoparticles; MMS: Multilayer micro-dispersing system; MSN: Mesoporous silica nanoparticles; DOX:CS/CMCS-NGs/Qu-M-ALG-Beads: DOX-chitosan complex incorporating carboxymethyl chitosan nanogels in the core of MMS and querctin modified alginate beads; AUC: Area under the curve; PO: per os.; BA: Bioavailability; SD rats: Sprague-Dawley rats.