PLGA-based nanoparticles: An overview of biomedical applications

Layered double hydroxides (LDHs) are a class of ionic lamellar compounds made up of positively charged brucite-like layers with an interlayer region containing charge compensating anions and solvation molecules. Delamination of LDHs is an interesting route for producing positively charged thin platelets with a thickness of a few atomic layers, which can be used as nanocomposites for polymers or as building units for making new designed organic-inorganic or inorganic-inorganic nanomaterials. The synthesis of nanosized LDH platelets can be generally classified into two approaches, bottom-up and top-down. It requires modification of the LDH interlamellar environment and then selection of an appropriate solvent system. In DDS intercalated LDHs, the aliphatic tails of the DDS- anions exhibit a high degree of interdigitation in order to maximize guest-guest dispersive interactions. Bellezza reported that the LDH colloids can also been obtained by employing a reverse microemulsion approach.

Recent advances in the synthesis and application of layered double hydroxide (LDH) nanosheets.

The lack of safe and efficient gene-delivery methods is a limiting obstacle to human gene therapy. Synthetic gene-delivery agents, although safer than recombinant viruses, generally do not possess the required efficacy. In recent years, a variety of effective polymers have been designed specifically for gene delivery, and much has been learned about their structure–function relationships. With the growing understanding of polymer gene-delivery mechanisms and continued efforts of creative polymer chemists, it is likely that polymer-based gene-delivery systems will become an important tool for human gene therapy.

Design and development of polymers for gene delivery

Stimuli-reponsive polymers and their bioconjugates

The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less

Nonviral Vectors for Gene Delivery

Inorganic Layered Double Hydroxides as Nonviral Vectors

pH-sensitive cationic polymer gene delivery vehicle: N-Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer.

Enhanced transfection efficiency of PAMAM dendrimer by surface modification with L-arginine.

The inorganic layered double hydroxide support, Mg4Al2(OH)12(NO3)2·mH2O, could be obtained by coprecipitation in aqueous solution; the interlayered NO3− anions can be replaced by biomolecules such as cytidine 5′-monophosphate, adenosine 5′-monophosphate, guanosine 5′-monophosphate and adenosine 5′-triphosphate to form new biomolecule–LDH hybrids. Upon intercalating these biomolecules into hydroxide layers, the interlayer distance increases from 8.7 A
(for NO3−) to 14.5 A, 16.9 A, 18.4 A, and 19.4 A, respectively. According to spectroscopic analysis, it is also found that the intercalated biomolecules maintain their chemical properties unchanged in the interlayer space of the layered double hydroxide. Furthermore, the
isotope dilution test for the transfer efficiency of [γ-32P] ATP–LDH hybrid into eucaryotic cells verifies reproducibly much higher transfer efficiency of the hybrid than for ATP molecules alone due to the charge neutralization of anionic phosphate molecules by cationic hydroxide layers in the hybrid. These experimental data suggest the potential usefulness of LDHs as innovative inorganic reservoirs and delivery carriers for genes, drugs, and other biomolecules.

Cellular uptake behavior of [γ-32P] labeled ATP–LDH nanohybrids

A barbell-like ABA-type triblock copolymer, poly(l-lysine) dendrimer-block-poly(ethylene glycol)-block-poly(l-lysine) dendrimer (PLLD-PEG-PLLD), was synthesized by the liquid-phase peptide synthesis method. The self-assembling complex formation of the third and fourth generation of the copolymer with plasmid DNA was studied. 1H NMR and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) were used for the characterization of the synthesized copolymer. The self-assembling behavior of the 3rd and 4th generations of the copolymer with plasmid DNA was investigated by electrophoretic mobility shift assay, DNase I protection assay, and ethidium bromide exclusion assay. We observed great differences in the self-assembling ability of the 3rd and 4th generations of the polymer. This suggests that the number of positively charged amines per polymer molecule should be an important factor for the potential for self-assembling complex formation with DNA. Atomic force microscopy (...

Synthesis of a Barbell-like Triblock Copolymer, Poly(l-lysine) Dendrimer-block-Poly(ethylene glycol)-block-Poly(l-lysine) Dendrimer, and Its Self-Assembly with Plasmid DNA

Jong-Sang Park

Papers

Inorganic Layered Double Hydroxides as Nonviral Vectors

pH-sensitive cationic polymer gene delivery vehicle: N-Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer.

Enhanced transfection efficiency of PAMAM dendrimer by surface modification with L-arginine.

Cellular uptake behavior of [γ-32P] labeled ATP–LDH nanohybrids

Synthesis of a Barbell-like Triblock Copolymer, Poly(l-lysine) Dendrimer-block-Poly(ethylene glycol)-block-Poly(l-lysine) Dendrimer, and Its Self-Assembly with Plasmid DNA