Potential Drug Delivery Agents Research Articles

GeSe nanoclusters as potential drug delivery agent for anti-cancer drugs: First-principles study

For effective drug delivery, a drug carrier that is biocompatible, antitoxic, and appropriate for drug loading/release is required. Here, GeSe nanoclusters are investigated as potential drug delivery for anti-cancer drugs using density functional theory (DFT) calculations. They are dynamically and energetically stable with abundant active sites that facilitate binding with drugs. The anti-cancer drugs, adrucil and hydroxyurea, are successfully loaded on the nanoclusters with adsorption energy ∼ -0.7 eV. Interestingly, no chemical bonds were formed between the drug and the nanocluster highlighting the robust non-covalent interactions (NCI). These slight changes in the electronic properties after drug adsorption are confirmed by the partial density of states, natural bond orbital (NBO) and NCI analysis, and UV–vis spectra. This moderate adsorption without notable changes in the electronic structure facilitates the drug release at the infected tissue. Therefore, GeSe nanoclusters with appropriate electronic and drug adsorption/release properties represent a viable drug delivery agent.

Development and Evaluation of Biotin Functionalized Fullerenes for the Delivery of Irinotecan to Colon Tumors.

Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy. The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex. Fullerene (C60) has been observed as a potential drug delivery agent and the aminefunctionalized C60-NH2 was synthesized by functionalizing ethylenediamine on the surface of C60. The PEI functionalized C60 was further synthesized by polymerization of aziridine on the surface of C60- NH2. Biotin was attached by an amide linkage to C60-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C60-PEI-Biotin/IRI). The C60-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan. The results showed that C60-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. Statistical studies confirmed less tumor index and tumor burden in the case of conjugate when compared to irinotecan. It is hypothesized that the conjugate (C60-PEI-Biotin/IRI) could cross the cell membrane easily through overexpressed biotin receptors on the cell surface of colon cancer cells and showed better efficacy and less toxicity in comparison to IRI in the colon cancer rat model.

Novel morphologies of mesoporous hierarchically assembled nanostructured hydroxyapatite particles: Influence of some synthesis conditions

Hierarchically assembled nanostructured apatitic (HANA) mesoporous particles have been hailed as potential drug delivery agents. However, their synthesis is intricate, and synthesis process parameters critically affect their formation. This investigation comprehensively evaluated the effects of both temperature and duration of hydrothermal heating on the architecture and structure of HANA particles. Variations in temperature and heating duration unfolded various HANA particle morphologies, including bundle-like, flower-like, dumbbell-like, and spherical-ended dumbbell-like particles. All morphologies exhibited monolithic apatitic structures with varying crystallinity and lattice strain. Also, particles exhibited mesoporous structures with superior surface area (16–23 m2g-1) and pore volume (0.009–0.048 cm3g-1). Spherical-ended dumbbell-like particles displayed strong drug encapsulation efficiency and improved pharmacokinetics in simulated body conditions based on their ionic release rate, drug loading, and release rate testings. Therefore, an amalgamation of amazing properties of HANA particles proposed their therapeutic applications as agents for controlled drug administration and tissue restoration multifunctions.

Guanidinium-Functionalized Flexible Azaproline Transporter for Efficient Intracellular Delivery of Proapoptotic Peptide and PDL1 Antisense Morpholino Oligo in Human Carcinoma Cells In Vitro.

Cell-penetrating peptides (CPPs) are structurally diverse sophisticated tools endowed with high arginine content, amphipathicity, and well-adopted suitable secondary structures. Despite its capability of breaching the lipid barriers, CPP has major limitations such as in vivo metabolic instability, poor bioavailability, and reduced endosomal escape tendency, which are yet to be improved. In this context, we first have introduced a new class of cellular transporter having a guanidinium-functionalized δ-azaproline (δ-azp)-containing peptide where the δ-azp structurally resembles the "proline" amino acid having an additional "N" at the δ-position. This non-natural peptidic backbone was found to impart proteolytic stability, as reported earlier by our group. Herein, we report the synthesis of a flexible azaproline-tetraguanidinium transporter named FAT along with a revised scalable methodology for δ-azp compared to our previously reported procedure. FAT shows a random-coil-like structure as determined by CD spectroscopy, and is hence structurally different from the polyproline PPII helix. Direct translocation is predicted to be the possible mode of the cellular entrance of FAT into CHO cells when the "Bodipy" fluorophore is covalently attached as the cargo. Simultaneously, two other macromolecular therapeutics, e.g., proapoptotic domain peptide (PAD, a 14-mer peptide) and programmed death ligand 1 (PDL1) morpholino (a 25-mer antisense oligo), were successfully conjugated with FAT and delivered into human carcinoma cells, and their efficacy was analyzed by MTT assay and western blot technique, respectively. Having obtained promising results in internalizing different types of cargos, FAT could be envisaged as a potential drug delivery agent as an alternative to natural CPPs for future application.

Physico-Mechanical Properties of Commercially Available Tissue Conditioner Modified with Synthesized Chitosan Oligosaccharide.

This study aims to compare the hardness, sorption and solubility of commercially available tissue conditioner [TC] modified with chitosan [CS] and synthesized chitosan oligosaccharide [COS] in antifungal concentration. COS was synthesized by acid hydrolysis and characterized by FTIR and XRD. Experimental materials were formulated by incorporating each per gram of TC powder with effective antifungal concentration of chitosan 1.02 mg (Group 1: TC-CS) and 0.51 mg COS (Group 2: TC-COS). A commercially available TC was used as control (Group 0: CTC). Shore A hardness test was performed according to ASTM D 2240-05 (2010) standards on samples stored in dry environment, distilled water (DW) and artificial saliva (AS) at 37 °C (n = 5 per group). Percent weight changes (n = 5 per group) after storage in DW and AS was used to record sorption and solubility. One-way Anova with post hoc Tukey’s test was applied. FTIR and XRD confirmed low molecular weight and amorphous nature of COS. Experimental groups had higher Shore A hardness values; however, these changes were not significant. Greatest variations in durometer values (p ≤ 0.05) were observed during the first 24 h. Experimental groups had higher (p ≤ 0.05) percentage sorption and solubility. Samples stored in DW had significantly higher (p = 0.019) sorption, whereas material had higher (p = 0.005) solubility in AS. Mean solubility values in both immersion mediums was highest for Group 2, followed by group 1 and group 0. In addition, significant (p ≤ 0.05) increase in solubility upon aging was noted for each material. Experimental tissue conditioner had higher hardness, sorption and solubility. However, these changes are not substantial to interfere with their tissue healing property. Therefore, these materials may be considered and explored further as potential antimicrobial drug delivery agent for denture stomatitis patients.

Multiple regulation and targeting effects of borneol in the neurovascular unit in neurodegenerative diseases.

Efficient delivery of brain-targeted drugs is highly important for the success of therapies in neurodegenerative diseases. Borneol has several biological activities, such as anti-inflammatory and cell penetration enhancing effect, and can regulate processes in the neurovascular unit (NVU), such as protein toxic stress, autophagosome/lysosomal system, oxidative stress, programmed cell death and neuroinflammation. However, the influence of borneol on NVU in neurodegenerative diseases has not been fully explained. This study searched the keywords 'borneol', 'neurovascular unit', 'endothelial cell', 'astrocyte', 'neuron', 'blood-brain barrier', 'neurodegenerative diseases' and 'brain disease' in PubMed, BioMed Central, China National Knowledge Infrastructure (CNKI) and Bing search engines to explore the influence of borneol on NVU. In addition to the principle and mechanism of penetration of borneol in the brain, this study also showed its multiple regulation effects on NVU. Borneol was able to penetrate the blood-brain barrier (BBB), affecting the signal transmission between BBB and the microenvironment of the brain, downregulating the expression of inflammatory and oxidative stress proteins in NVU, especially in microglia and astrocytes. In summary, borneol is a potential drug delivery agent for drugs against neurodegenerative diseases.

Evaluation of protein functionalized gold nanoparticles to improve tamoxifen delivery: synthesis, characterization, and biocompatibility on breast cancer cells

In the study, human serum albumin functionalized gold nanoparticles (HSA-AuNPs) were fabricated benefiting from the unique properties of HSA and AuNP to achieve tamoxifen delivery to breast cancer cells for renewing tumor targeting with unconventional nanoparticles. The release pattern of tamoxifen (TMX), the cell viability, oxidative DNA damage, and total antioxidant capacity of HSA-AuNP with and without TMX were assessed on BT-474 and MDA MB-231 breast cancer cell lines. The outcomes indicated that TMX entrapped HSA-AuNP can induce cancer cell death in a dose-dependent aspect and could be proved via further studies as a potential drug delivery agent.

Dendrimer applications: a brief review

: Dendrimers are highly branched three-dimensional macromolecules with a highly controlled structure, a single molecular weight, numerous controllable dendritic branches and peripheral functionalities, as well as the tendency to adopt an ellipsoid or spheroid shape once a certain size is reached. These features have made them attractive for application in pharmaceutical and medicinal chemistry in gene transfection, as medical imaging agents, and as drug carriers in potential drug delivery agents. The incorporation of metallic species into dendritic molecules has also been reported; the focus has been on organometallic dendrimers with metallic species only at specific positions of the molecules, such as the core, dendritic branches and the periphery, studied for their magnetic, electronic, and photo-optical or catalytic properties. Dendrimers have been investigated for optoelectronic applications (adsorption, emission, laser emission, nonlinear optics) through the encapsulation of active units by dendritic branches, core and peripheral. This review briefly discusses their use in nanomedicine, cancer treatment, treatment of other diseases, tissue repair, catalysis and applications in OLEDs and solar cells.

Polymeric Nanoparticles for Antimicrobial Therapies: An Up-To-Date Overview.

Despite the many advancements in the pharmaceutical and medical fields and the development of numerous antimicrobial drugs aimed to suppress and destroy pathogenic microorganisms, infectious diseases still represent a major health threat affecting millions of lives daily. In addition to the limitations of antimicrobial drugs associated with low transportation rate, water solubility, oral bioavailability and stability, inefficient drug targeting, considerable toxicity, and limited patient compliance, the major cause for their inefficiency is the antimicrobial resistance of microorganisms. In this context, the risk of a pre-antibiotic era is a real possibility. For this reason, the research focus has shifted toward the discovery and development of novel and alternative antimicrobial agents that could overcome the challenges associated with conventional drugs. Nanotechnology is a possible alternative, as there is significant evidence of the broad-spectrum antimicrobial activity of nanomaterials and nanoparticles in particular. Moreover, owing to their considerable advantages regarding their efficient cargo dissolving, entrapment, encapsulation, or surface attachment, the possibility of forming antimicrobial groups for specific targeting and destruction, biocompatibility and biodegradability, low toxicity, and synergistic therapy, polymeric nanoparticles have received considerable attention as potential antimicrobial drug delivery agents. In this context, the aim of this paper is to provide an up-to-date overview of the most recent studies investigating polymeric nanoparticles designed for antimicrobial therapies, describing both their targeting strategies and their effects.

Amphiphilic block copolymers as potential drug delivery agent for curcumin: A review

Abstract Curcumin is a polyphenolic natural material, and it is active ingredient of the dietary spice turmeric. The medicinal use of this plant has been known from the ancient times. Many natural materials have been used in traditional medicines for thousands of years and have shown promise as a source of components for the development of new drugs. Turmeric is one of the most popular medicinal herbs, with a wide range of pharmacological activities such as antioxidizing, antibacterial, anti-protozoal, anti-microbial, anti-malarial, anti-inflammatory, anti-proliferative, anti-angiogenic, anti-tumor, and anti-aging properties. Various studies on curcumin suggest that it has potential as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Curcuminoids have the potential to cure immune related, metabolic diseases and cancer due to a vast number of biological targets and virtually no side effects. Several in vitro and in vivo studies support the bioactivity of curcumin. However, potential medical application of curcumin is hindered because of low water solubility and extremely high metabolism rate. Hence, potential application of the molecule depends on effective encapsulation of the molecule in suitable non-toxic drug delivery agents to increase solubility and retention time. In this systematic review, we assess the potential of curcumin as a bioactive substance and the hindrances in its application. We also explore the possibilities of using amphiphilic block copolymers to encapsulate, retain, and release the drug molecule to enhance its usability.

Preparation and Characterization of Poly(l-lactide-co-glycolide-co-ε-caprolactone) Porous Microspheres

Porous microspheres have interconnecting external and internal pore structure resulting in enormous specific surface area and have drawn attention for drug delivery. In this work, poly(l-lactide-co-glycolide-co-ε-caprolactone) (PLLGC) porous microspheres were prepared by a combined solvent evaporation and particle leaching method using gelatin as a porogen. The effects of preparation parameters on the morphologies of the porous microspheres were studied. The resultant microspheres showed porous surfaces and a three-dimensional internal network structure with interconnecting pores. The porous microsphere size decreased with increasing stirring speed and decreasing PLLGC concentration. There were fewer micropores on the surfaces of the microspheres with increasing temperature. The number of the pores and pore size on the surface of the microspheres increased with increasing gelatin content. By appropriate control of these factors (stirring speed 300 rpm, PLLGC solution concentration 1.0 wt%, temperature 0 °C, and gelatin concentration 7.5 wt%), a suitable porous microsphere, with a mean diameter of 200 μm, was prepared as a potential drug delivery agent.

Biomimicked and CPMV-Imprinted Hollow Porous Zinc Phosphate Nanocapsules and Their Therapeutic Efficiency.

Hollow zinc phosphate nanocapsules (hZPNCs) are an alloplastic biomaterial that has been synthesized to deliver chemotherapeutic drugs in a sustained manner. A very simple one-pot synthesis approach has been employed to synthesize hZPNCs by using cowpea mosaic virus (CPMV) in the presence of phosphate buffer (PBS) (0.01 M PBS, pH ∼7.2) with zinc acetate precursor. The synthesis mechanism of hZPNCs relies on the basis of biomineralization, where the precursor molecules initiate mineralization with the help of amino acid residues present on the CPMV capsid. The synthesized hollow nanocapsules were of diameter ∼50-60 nm and porous shell with thickness of ∼4 nm. The cavity performed as a reservoir for the anticancer drugs (DOX and IM). The release kinetic studies show the positive aspect of hZPNCs to be labeled as drug delivery cargo for sustained delivery. In vitro cytotoxic studies of hZPNCs and hZPNCs-chemo drugs on HEK293, HEPG2, and K562 cells were performed. The cytotoxic studies show that hZPNCs-DOX and hZPNCs-IM arrest the cell cycle of carcinoma cells (HEPG2 and K562 cells) at relatively low IC50 and that the inhibition efficiency is dosage dependent. Furthermore, through HRTEM, in vitro cellular interactions of carcinoma cells with hZPNCs and chemo drug-loaded hZPNCs were confirmed by the cryo-sectioning of cells before and after the incubation. These studies revealed the likely endocytic pathway for the nanocapsules entering the cell and executing the specific action of delivering the anticancer drugs. Together, these results reveal the hZPNCs as potential sustained drug delivery agents.

Ultrasmall gold nanoparticles (2 nm) can penetrate and enter cell nuclei in an in vitro 3D brain spheroid model

The neurovascular unit (NVU) is a complex functional and anatomical structure composed of endothelial cells and their blood-brain barrier (BBB) forming tight junctions. It represents an efficient barrier for molecules and drugs. However, it also prevents a targeted transport for the treatment of cerebral diseases. The uptake of ultrasmall nanoparticles as potential drug delivery agents was studied in a three-dimensional co-culture cell model (3D spheroid) composed of primary human cells (astrocytes, pericytes, endothelial cells). Multicellular 3D spheroids show reproducible NVU features and functions. The spheroid core is composed mainly of astrocytes, covered with pericytes, while brain endothelial cells form the surface layer, establishing the NVU that regulates the transport of molecules. After 120 h cultivation, the cells self-assemble into a 350 µm spheroid as shown by confocal laser scanning microscopy. The passage of different types of fluorescent ultrasmall gold nanoparticles (core diameter 2 nm) both into the spheroid and into three constituting cell types was studied by confocal laser scanning microscopy. Three kinds of covalently fluorophore-conjugated gold nanoparticles were used: One with fluorescein (FAM), one with Cy3, and one with the peptide CGGpTPAAK-5,6-FAM-NH2. In 2D cell co-culture experiments, it was found that all three kinds of nanoparticles readily entered all three cell types. FAM- and Cy3-labelled nanoparticles were able to enter the cell nucleus as well. The three dissolved dyes alone were not taken up by any cell type. A similar situation evolved with 3D spheroids: The three kinds of nanoparticles entered the spheroid, but the dissolved dyes did not. The presence of a functional blood-brain barrier was demonstrated by adding histamine to the spheroids. In that case, the blood-brain barrier opened, and dissolved dyes like a FITC-labelled antibody and FITC alone entered the spheroid. In summary, our results qualify ultrasmall gold nanoparticles as suitable carriers for imaging or drug delivery into brain cells (sometimes including the nucleus), brain cell spheroids, and probably also into the brain. Statement of significance3D brain spheroid model and its permeability by ultrasmall gold nanoparticles.We demonstrate that ultrasmall gold nanoparticles can easily penetrate the constituting cells and sometimes even enter the cell nucleus. They can also enter the interior of the blood-brain barrier model. In contrast, small molecules like fluorescing dyes are not able to do that. Thus, ultrasmall gold nanoparticles can serve as carriers of drugs or for imaging inside the brain.

Biofabrication of Diatom Surface by Tyrosine‐Metal Complexes:Smart Microcontainers to Inhibit Bacterial Growth

AbstractThis study explores the potential of a highly biocompatible golden brown algal cell, diatom, as a drug carrier to the bacterial cell. The strong interaction between diatom and bacteria that occur in the microenvironment, lead us to pave the way for exciting new directions where diatom can be used to address several bacterial infections. The surface of diatom frustules was modified with self‐assembled antibacterial aromatic amino acid conjugates, Tyr‐ZnII. Microscopy and spectroscopy observations confirmed the deposition of Tyr‐ZnII over diatom frustules. Diatoms can work as living microcontainers to store the toxic metal (drug) ions and therefore can be utilized as potential drug delivery agents to kill the clinically relevant bacteria. Due to antibacterial property of zinc ions, Tyr‐ZnII conjugates inhibits bacterial growth and diatom frustules were utilized as Tyr‐ZnII carrier for controlled release of zinc to the bacterial cell.

Efficient microwave synthesis, functionalisation and biocompatibility studies of SPION based potential nano-drug carriers

Superparamagnetic iron oxide nanoparticles are much desired for various biomedical applications due to their biocompatible, biodegradable and superparamagnetic nature. In contrast to high-temperature synthesis methods, present study investigates the facile low-temperature co-precipitation process without inert atmosphere. For its efficient, homogenous, in core heating and environment friendly nature microwave energy at two powers of 180 and 450 W was used for synthesis and functionalisation of nanoparticles. It was found in the study, that microwave power plays a decisive role in controlling the size, coating and drug loading percentage of the particles. The synthesis process has been made more economic and simpler by the use of domestic oven, and serine coated particles with mean sizes around 6.8 and 10 nm, narrow size distribution (standard deviations of 1.4 and 1.6 nm), almost rectangular shape and magnetization values of approx. 48 and 42 emu/g were obtained at 180 and 450 W power, respectively. Particles were found to have properties such as near to zero remanence and coercivity, good crystallization and colloidal stability. The biocompatibility of the uncoated and serine coated particles was confirmed by the MTT assay on A 549 epithelial cells. Synthesized particles were found to have all the suitable properties for potential application in biomedical fields. Doxorubicin hydrochloride was loaded efficiently on both the synthesized particles, with loading efficiency obtained up to 6.8% wt/wt, for assessing their suitability as potential drug delivery agents.

Targeted Killing of Monocytes/Macrophages and Myeloid Leukemia Cells with Pro-Apoptotic Peptides.

Several cells of myeloid origin, such as monocytes and macrophages are involved in various human disorders, including cancer and inflammatory diseases. Hence, they represent attractive therapeutic targets. Here we developed three lytic hybrid peptides, by fusing a monocyte- and macrophage-binding peptide to pro-apoptotic peptides, and investigated their killing potency on blood monocytes, macrophages, and leukemia cells. We first showed that the targeting NW peptide is effective for depleting monocytes from whole peripheral blood mononuclear cells (PBMCs). Incubating the cells with biotin-conjugated NW peptide, and the subsequent capture on streptavidin-conjugated magnetic beads, depleted monocytes from the PBMCs. The NW peptide also depleted myeloid leukemia blasts from patient PBMCs. The treatment of the PBMCs with the lytic hybrid NW-KLA peptide killed monocytes, but not lymphocytes and primary mammary epithelial cells. Additionally, the fusion peptide exhibited a potent toxicity against macrophages and leukemia cells. The free lytic KLA peptide did not affect cells. Similarly, a second lytic hybrid peptide killed macrophages, leukemia cell lines, and blood leukemia blasts from patients with acute and chronic myeloid leukemia. The IC50 towards target cells were in the low macromolar range (4–12 µM). Overall, the data indicate that the NW peptide could be a potential drug delivery agent for monocytes, macrophages, and leukemia cells. Moreover, the engineered lytic hybrid peptides acting alone, or in combination with other therapeutic agents, might benefit many cancer patients and overcome drug resistance.

Minocycline-loaded calcium polyphosphate glass microspheres as a potential drug-delivery agent for the treatment of periodontitis.

Background: Periodontitis is an inflammatory disease with a bacterial etiology that affects the supporting structures of the teeth and is a major cause of tooth loss. The objective of this study was to investigate the drug loading and in vitro release of minocycline from novel calcium polyphosphate microspheres intended for use in treating periodontitis. Methods: Calcium polyphosphate coacervate, produced by a precipitation reaction of calcium chloride and sodium polyphosphate solutions, was loaded with minocycline and subsequently used to produce microspheres by an emulsion/solvent extraction technique. Microspheres classified by size were subjected to a 7-day elution in a Tris-buffer solution under dynamic conditions. The physicochemical characteristics of the drug-loaded microspheres were investigated using scanning electron microscopy, particle size analysis, Phosphorus-31 Nuclear Magnetic Resonance spectroscopy, and Inductively Coupled Plasma Optical Emission Spectroscopy. Drug loading and release were determined using ultraviolet -visible (UV/VIS) spectrophotometry. Results: Minocycline-loaded calcium polyphosphate microspheres of varying size were successfully produced, with small and large microspheres having volume mean diameters of 22 ± 1 µm and 193 ± 5 µm, respectively. Polyphosphate chain length and calcium to phosphorus mole ratio remained stable throughout microsphere production. Drug loading was 1.64 ± 0.16, 1.35 ± 0.55, and 0.84 ± 0.14 weight% for the coacervate and large and small microspheres, respectively, corresponding to mean encapsulation efficiencies of 81.7 ± 12.2 % and 50.9 ± 3.9 % for the large and small microspheres. Sustained drug release was observed in vitro over a clinically relevant 7-day period, with small and large microspheres exhibiting similar elution profiles. Antibiotic release generally followed microsphere degradation as measured by Ca and P ion release. Conclusions: This study demonstrated successful drug loading of calcium polyphosphate microspheres with minocycline. Furthermore, in vitro sustained release of minocycline over a 7-day period was observed, suggesting potential utility of this approach for treating periodontitis.

A Perspective Review on the Role of Nanomedicine in the Modulation of TNF-TNFR2 Axis in Breast Cancer Immunotherapy.

In the past decade, nanomedicine research has provided us with highly useful agents (nanoparticles) delivering therapeutic drugs to target cancer cells. The present review highlights nanomedicine applications for breast cancer immunotherapy. Recent studies have suggested that tumour necrosis factor (TNF) and its receptor 2 (TNFR2) expressed on breast cancer cells have important functional consequences. This cytokine/receptor interaction is also critical for promoting highly immune-suppressive phenotypes by regulatory T cells (Tregs). This review generally provides a background for nanoparticles as potential drug delivery agents for immunomodulators and further discusses in depth the potential of TNF antagonists delivery to modulate TNF-TNFR2 interactions and inhibit breast cancer progression.

Methyl methacrylate modified chitosan: Synthesis, characterization and application in drug and gene delivery

A methyl methacrylate (MMA) modified chitosan (CS) conjugate (CSMMA) has been synthesized by a green method via Michael addition reaction between CS and MMA in ethanol. The synthesized conjugate was characterized by FT-IR, 1H NMR, X-ray diffraction spectrometry and SEM analysis. The results confirmed that CS was covalently linked to MMA yielding a highly porous framework. The uses of CSMMA were analyzed as a potential gene and drug delivery agent. CSMMA proved to be a reasonably good gene delivery agent based on transfection efficiency studies in mammalian cancer cell lines (A549, HeLa and HepG2). For drug delivery studies, nanoparticles of the CSMMA biopolymer were prepared by ionic gelation method with sodium tripolyphosphate (TPP). The prepared nanoparticles were characterized in terms of FE-SEM, DLS and zeta potential. In vitro drug release study of curcumin loaded CSMMA nanoparticles showed its maximal entrapment efficiency up to 68% and the drug release was more rapid at a pH (5.0) lower than physiological pH.

Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6

Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs displayed spherical morphology around 300 nm and were negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 µg/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6+ carcinomas. Statement of SignificanceThe v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans.v6 Fab-PLGA NPs strongly bound to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences on the stability of Fab-functionalized NPs.These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration.