Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin

Abstract

BackgroundThis study was performed to develop a functional poly(D,L-lactide-co-glycolide)- poly(ethylene glycol) (PLGA-PEG)-bearing amino-active end group for peptide conjugation.Methods and resultsPLGA was preactivated following by copolymerization with PEG diamine. The resulting amphiphilic PLGA-PEG copolymer bearing 97.0% of amino end groups had a critical micelle concentration of 3.0 × 10−8 mol/L, and the half-effective inhibition concentration (IC50) of the prepared PLGA-PEG nanoparticles was >100 mg/mL, which was much higher than that of PLGA nanoparticles (1.02 ± 0.37 mg/mL). The amphiphilic properties of PLGA-PEG spontaneously formed a core-shell conformation in the aqueous environment, and this special feature provided the amino group on the PEG chain scattered on the surface of PLGA-PEG nanoparticles for efficient peptide conjugation. The peptide-conjugated PLGA-PEG nanoparticles showed three-fold higher uptake than peptide-free PLGA-PEG nanoparticles in a SKOV3 cell line with high expression of epidermal growth factor receptor. Both peptide-conjugated and peptide-free PLGA-PEG nanoparticles were used as nanocarriers for delivery of doxorubicin. Although the rate of release of doxorubicin from both nanoparticles was similar, drug release at pH 4.0 (500 U lipase) was faster than at pH 7.4. The IC50 of doxorubicin-loaded peptide-conjugated PLGA-PEG nanoparticles in SKOV3 cells (0.05 ± 0.03 μg/mL) was much lower (by 62.4-fold) than that of peptide-free PLGA-PEG nanoparticles (3.12 ± 1.44 μg/mL).ConclusionThis in vivo biodistribution study in SKOV3 tumor-bearing mice was further promising in that accumulation of doxorubicin in tumor tissue was in the order of peptide-conjugated PLGA-PEG nanoparticles > peptide-free PLGA-PEG nanoparticles > doxorubicin solution.

Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting

“…Some researchers have hypothesised that the improvement in the aerosolisation of powders containing L-leucine is due to its molecular structure, specifically to the hydrophobic alkyl side chain [17,37]. Cellular studies in three macrophage cell lines showed low toxicity for both PLGA nano-and microparticles, which correlates with the results reported in literature (e.g., [38,39]) as the high safety profile of PLGA has been extensively reported (it was approved for human use by the Food and Drug Administration and the European Medicine Agency). PLGA suffers hydrolytic degradation in the body, and degrades into its nontoxic metabolites lactic and glycolic acid.…”

Comparison between two multicomponent drug delivery systems based on PEGylated-poly (l-lactide-co-glycolide) and superparamagnetic nanoparticles: Nanoparticulate versus nanocluster systems

“…2. The following signals were assigned as follows: 5.30-5.17 ppm to the -CH-of the lac-tide, 4.90-4.5 ppm to the -CH2-of the glycolide, 3.61-3.55 ppm to the -CH2-of the ethylene glycol and at 1.65 ppm to the -CH3 of lactide, thus confirming the conjugation of PLGA chains with NH2-PEG-NH2 [37]. The HMQC spectrum (Figure S7) can further confirm the amide bond formed after the conjugation step.…”

Ocular Penetration of fluorometholone-loaded PEG-PLGA Nanoparticles Functionalized With cell-penetrating Peptides

“…The spectrum was recorded at 298 K on a Varian VNMRS 400 MHZ spectrometer (Agilent Technologies, CA, USA). To calculate the PEGylation efficiency and percentage of mass relative (MR) of the m-PEG bound to the NHS-PLGA polymer, the following equations were used [17,26]…”