Lutein-Loaded, Biotin-Decorated Polymeric Nanoparticles Enhance Lutein Uptake in Retinal Cells

Abstract

Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood–retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA–PEG–biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA–PEG–biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was ≈56% and ≈75% for lutein-loaded PLGA and PLGA–PEG–biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA–PEG–biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA–PEG–biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake.

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

“…After 12 h, 1 mL of 50 mM NH 4 Cl was added to TAC-NMF-FITC and TAC-FITC solution to inactivate unreacted FITC. The final solution of FITC-labelled TAC-NMF and TAC was aliquoted and stored at −20°C until further use, as described in [ 29 , 33 , 34 ]. Figure 2 depicts the FITC conjugation reaction for TAC-NMF-FITC and TAC-FITC formation.…”

Recent Advances on Nanoparticle Based Strategies for Improving Carotenoid Stability and Biological Activity

“…Moreover, compared to free crocetin (589.7 µM), the PLGA crocetin NPs showed a lower IC 50 value (84.7 µM) in inhibiting human breast cancer cell MCF-7 ( Figure 8 B). Also, in a recent study Bolla, et al [ 47 ] used biotin-based PLGA-polyethylene glycol (PEG) for encapsulation of lutein to develop PLGA-PEG-lutein NPs (particle size, <250 nm; ZP, −27.3 mV; EE, 74.6%) and showed a sustained 100% in vitro release after 24 h. Furthermore, they showed a higher lutein intake by retinal pigment epithelial cell ARPE-19 from PLGA-PEG-lutein NPs than from both free lutein and PLGA- lutein NPs ( Figure 8 C), demonstrating that a combination of polymers could possess a greater potential in treating age-related macular degeneration.…”

“…Bioaccessibility is usually determined in vitro by simulating gastric condition with pepsin/HCl (pH 1–2) and intestinal condition with pancreatin/bile salt or trypsin (pH 7–7.5), followed by mimicking an absorption model using Caco-2 cell or dialysis bag [ 42 , 47 , 56 ]. Whereas, the absolute bioavailability in vivo is determined by simultaneous oral administration by gavage and intravenous injection into rats, followed by blood collection and bioactive component analysis at different time intervals and determination of pharmacokinetic parameters including AUC (area under the curve of bioactive component concentration versus time profile), C max (maximum concentration in blood), T max (time to reach maximum concentration in blood) and t 1/2 (time to reach half the maximum concentration) [ 44 ].…”

“…DMSO = dimethyl sulfoxide, PLGA = poly (lactic-co-glycolic acid), PEG-polyethylene glycol, FACS = fluorescence activated cell sorting, FITC = fluorescein isothiocyanate, GE = Guabiroba fruit extract, ROS = reactive oxygen species and IC 50 = half maximal inhibitory concentration. Adapted with permission from Pereira, et al [ 40 ], Hafezi Ghahestani, et al [ 49 ], and Bolla, et al [ 47 ].…”

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“…The anticancer properties of biotinylated nanosystems have received great attention from researchers ( Table 4 ) [ 118 ]. The era of biotinylated DDS has been started from the article published in 2004 by Russell-Jones et al It has been reported that the therapy of colon cancer (using Colo-26 xenograft model) with the biotin-labelled doxorubicin-hydroxypropylmethacrylic acid (Dox-HMPA) complex provides enhanced efficiency when compared to the control group.…”