Kinetically Controlled Cellular Interactions of Polymer-Polymer and Polymer-Liposome Nanohybrid Systems

Departments of †Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
Bioconjugate Chemistry (Impact Factor: 4.51). 02/2011; 22(3):466-74. DOI: 10.1021/bc100484t
Source: PubMed


Although bioactive polymers such as cationic polymers have demonstrated potential as drug carriers and nonviral gene delivery vectors, high toxicity and uncontrolled, instantaneous cellular interactions of those vectors have hindered the successful implementation In Vivo. Fine control over the cellular interactions of a potential drug/gene delivery vector would be thus desirable. Herein, we have designed nanohybrid systems (100-150 nm in diameter) that combine the polycations with protective outer layers consisting of biodegradable polymeric nanoparticles (NPs) or liposomes. A commonly used polycation polyethylenimine (PEI) was employed after conjugation with rhodamine (RITC). The PEI-RITC conjugates were then encapsulated into (i) polymeric NPs made of either poly(lactide-co-glycolide) (PLGA) or poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PEG-PLGA); or (ii) PEGylated liposomes, resulting in three nanohybrid systems. Through the nanohybridization, both cellular uptake and cytotoxicity of the nanohybrids were kinetically controlled. The cytotoxicity assay using MCF-7 cells revealed that liposome-based nanohybrids exhibited the least toxicity, followed by PEG-PLGA- and PLGA-based NPs after 24 h incubation. The different kinetics of cellular uptake was also observed, the liposome-based systems being the fastest and PLGA-based systems being the slowest. The results present a potential delivery platform with enhanced control over its biological interaction kinetics and passive targeting capability through size control.

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    • "PLGA50 : 50-chitosan (15 kDa) DCM 1.67 5-Fluorouracil 10 198∼280 23∼29 [58] R502H (12 kDa) DCM 5 Gentamicin 3.5 241∼252 6∼22 [59] RG502H (13.8 kDa) EA n/a Gentamicin 1∼5 3 2 0 1 3 ∼47 [60] PLGA75 : 25 (20 kDa) DCM 3, 6, 20 GFP siRNA 0.24, 0.6 224∼428 11∼58 [61] RG503 (34 kDa) DCM 5 Insulin 5 276 68 [50] RG503H (n/a) DCM 1.5 hgp100, TRP2 1 80 8∼40 [62] PLGA50 : 50 (30 kDa) DCM 3.3 LA 0.2, 3.85 300 49∼72 [63] RG502H (10–12 kDa) DCM 3 Ovalbumin 1.67 182 54 [64] PLGA50 : 50 (7–17 kDa) DCM 2.9 Ovalbumin 20 358 36 [65] PLGA50 : 50 (40–75 kDa) DCM 2 PEI-rhodamine B 0.5 117∼130 45∼75 [66] PLGA50 : 50 (n/a) DCM n/a pRedN-1 DNA n/a 998 10 [67] PLGA50 : 5 (45–75 kDa) DCM 1∼5 TIMP-1 (28 kDa) 0.2∼1.0 81∼433 62∼80 [68] "
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    ABSTRACT: In recent years, there have been a plethora of nanoengineering approaches for the development of poly(lactide- co -glycolide) (PLGA) nanoparticulate carrier systems. However, overlooking the multifaceted issues in the preparation and characterization of PLGA-based nanoparticles, many reports have been focused on their in vivo behaviors. It is imperative to fully assess technological aspects of a nanoencapsulation method of choice and to carefully evaluate the nanoparticle quality. The selection of a nanoencapsulation technique should consider drug property, nanoparticle quality, scale-up feasibility, manufacturing costs, personnel safety, environmental impact, waste disposal, and the like. Made in this review are the fundamentals of classical emulsion-templated nanoencapsulation methods used to prepare PLGA nanoparticles. More specifically, this review provides insight into emulsion solvent evaporation/extraction, salting-out, nanoprecipitation, membrane emulsification, microfluidic technology, and flow focusing. Innovative nanoencapsulation techniques are being developed to address many challenges existing in the production of PLGA-based nanoparticles. In addition, there are various out-of-the-box approaches for the development of novel PLGA hybrid systems that could deliver multiple drugs. Latest trends in these areas are also dealt with in this review. Relevant information might be helpful to those who prepare and develop PLGA-based nanoparticles that meet their specific demands.
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    • "The dendrimer conjugates and PEG–PLA copolymers were characterized by 1 H NMR as previously described [27] [28] [29]. The structure of G4-RITC–FA-OH and G5-RITC–FA-OH was also confirmed by UV/Vis. "
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    Journal of Controlled Release 05/2014; 191. DOI:10.1016/j.jconrel.2014.05.006 · 7.71 Impact Factor
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    • "The in vitro Gemcitabine release profiles from PLGem (Figure 3A) and GemPo (Figure 3B) were assessed in an aggressive human pancreatic carcinoma cell line, PANC1, which is well-known to exhibit Gemcitabine resistance, thus serving as an ideal model to investigate the roles of PLGem and GemPo in PDA [9]. As shown in Figure 3, PLGem and GemPo exhibited burst release of Gemcitabine in both PANC1 lysates and PBS, which peaked faster with regards to GemPo (28 h, Figure 3B) than with PLGem (47 h, Figure 3A), thus confirming the characteristic burst release profile associated with nanoparticle encapsulation [31]. Both PLGem and GemPo achieved sustained release of Gemcitabine for at least 7 days, consistent with the temporal control imparted by nanoparticles on drugs [16]. "
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