Abstract
Oral delivery is considered the preferred route of administration due to its convenience and favorable compliance. Here, docetaxel (DTX) loaded polylactic-co-glycolic acid (PLGA) nanoparticles, coated with polyethyleneimine–folic acid (PEI-FA) and polyethyleneimine–borneol (PEI-BO), were designed to enhance oral absorption (FA/BO-PLGA-NPs). The FA/BO-PLGA-NPs were spherical and smooth with an average size of (137.0 ± 2.1) nm. Encapsulation efficiency (EE%) and drug loading (DL%) were (80.3 ± 1.8)% and (2.3 ± 0.3)%, respectively. In vitro release studies showed that approximately 62.1% of DTX was released from FA/BO-PLGA-NPs in media at pH 7.4. The reverted gut sac method showed that the absorption of FA/BO-PLGA-NPs in the intestines was approximately 6.0 times that of DTX. Moreover, cellular uptake suggested that the obtained FA/BO-PLGA-NPs could be efficiently internalized into Caco-2 cells via FA-mediated active targeting and BO-mediated P-glycoprotein (P-gp) inhibition. Pharmacokinetics study demonstrated that after oral administration of DTX at a dose of 10 mg/kg in FA/BO-PLGA-NPs, the bioavailability of FA/BO-PLGA-NPs was enhanced by approximately 6.8-fold compared with that of DTX suspension. FA/BO-PLGA-NPs caused no obvious irritation to the intestines. Overall, the FA/BO-PLGA-NP formulation remarkably improved the oral bioavailability of DTX and exhibited a promising perspective in oral drug delivery.
Highlights
At present, cancer is one of the leading causes of death in humans [1]
The weak negative charge of polylactic-co-glycolic acid (PLGA) nanoparticles often leads to low bioavailability, which is caused by limits on their ability to interact with negatively charged plasmids and intracellular uptake [13]
The results showed that folate-receptor-mediated endocytosis was one of the major pathways of nanoparticle transmembrane entry into cells [23,24]
Summary
Cancer is one of the leading causes of death in humans [1]. Chemotherapy is an important part of the treatment of cancer, and most of the anticancer drugs used in clinical practice are mainly injected. Without nephrotoxicity to the body and kidney retention, folate-modified nanoparticles have been studied to explore the mechanism of FA receptors overexpressed on the surface of intestinal epithelial cells [20,21,22]. DTX-loaded PLGA-NPs were prepared, modified with PEI coupling FA (FA-PEI) or BO (BO-PEI) (FA/BO-PLGA-NPs), and the mechanism of enhancing oral absorption was investigated. The characteristics of the designed FA/BO-PLGA-NPs were as follows: (i) drug release from FA/BO-PLGA-NPs and intestinal absorption of nanoparticles, (ii) cell uptake of FA/BO-PLGA-NPs by confocal laser scanning microscopy (CLSM) and BD FACS caliber flow cytometer, and (iii) the relative bioavailability and cytotoxicity or irritation of FA/BO-PLGA-NPs compared with DTX suspension was studied in rats
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