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Breast cancer is one of the most common cancers and a significant cause of death in females worldwide. For effective breast cancer treatment, using systems with a promising delivery of anticancer agents is an important strategy. Peptide 18 (P18), a tumorhoming peptide, shows a high binding affinity toward breast cancer cells. Nanoliposomes are known to have enhanced accumulation ability in tumors with longer systemic circulation. In this study, Poly (2-ethyl-2-oxazoline) (PEtOx) polymers conjugated with DOPE are used to prepare PEtOx-DOPE nanoliposomes. BikDD, a mutant form of the Bik gene and a member of the BH3-only proapoptotic genes, mimics the constitutively phosphorylated form of the gene. To the best of our knowledge, this study presents a novel approach by investigating P18-conjugated PEtOx-DOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of BikDD to the AU565 breast cancer model. A site-directed mutated BikDD was loaded into P18-PEtOx-DOPE nanoliposomes, and the targeted drug delivery system was assessed in in vitro and in vivo breast cancer models for efficiency, safety, and efficacy. The increased Bik mRNA expression levels in AU565 cells suggest a high effectiveness of the targeting PEtOx-DOPE nanoliposomes. Following the in vitro studies, the delivery of BikDD by P18-PEtOx-DOPE nanoliposomes was analyzed in CD-1 nude mice models. The animal study showed no significant difference in the tumor volume of the CD-1 nude mice treated with P18-PEtOx-DOPE-BikDD nanoliposomes compared to the free delivery of BikDD. Our preclinical studies suggest that P18-PEtOx-DOPE-BikDD nanoliposomes may be promising gene carriers for targeted breast cancer therapy. Thus, further studies should be carried out to determine the prolonged use of this drug delivery system in breast cancer therapy. [ABSTRACT FROM AUTHOR]

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Background: Nanocarrier-based systems have cultivated significant improvements in prostate cancer therapy. However, the efforts are still limited in clinical applicability, and more research is required for the development of effective strategies. Here, we describe a novel nanoliposomal system for targeted apoptotic gene delivery to prostate cancer. Methods: Poly (2-ethyl-2-oxazoline) (PEtOx) dioleoyl phosphatidylethanolamine (DOPE) nanoliposomes were conjugated with the prostate-specific membrane antigen (PSMA)-targeting peptide GRFLTGGTGRLLRIS (P563) and loaded with BikDDA, a mutant form of the proapoptotic Bik. We selected 22Rv1 cells with moderate upregulation of PSMA to test the in vitro uptake, cell death, and in vivo anticancer activity of our formulation, P563-PEtOx-DOPE-BikDDA. Results: BikDDA was upregulated in 22Rv1 cells, inducing cell death, and CD-1 nude mice xenografts administered with the formulation showed significant tumor regression. Conclusion: We suggest that P563-PEtOx-DOPE-BikDDA nanoliposomes can serve as prominent gene carriers against prostate cancer. [ABSTRACT FROM AUTHOR]

The incidence of breast cancer has increased considerably in recent years. Many efforts have been made to develop various nano‐drug delivery systems with specific properties to achieve effective and specific therapy. The stealthy nanoliposomes are the most successful and promising candidates for providing targeted tumor therapy. In this paper, a synthesized PEtOx‐DOPE (poly(2‐Ethyl 2‐Oxazoline)‐Dioleoyl Phosphatidylethanolamine) copolymer was equipped with a breast cancer‐recognizing tumor‐homing peptide to achieve cell‐specific delivery. The prepared liposomes provided stability for 6 months, and their hydrodynamic diameters are around 100 nm. Targeted liposomes remarkably exhibited 8 times higher cellular internalization in comparison with the nontargeted cells in flow cytometry and confocal microscopy. Furthermore, liposome constructs displayed slight toxicity on HaCaT cells when treated with high doses. Hence, Peptide 18‐conjugated PEtOx‐DOPE liposome systems can serve as favorable candidates in breast cancer‐targeted therapy. [ABSTRACT FROM AUTHOR]

Liposome surface modifications serve great potential applications of liposomes, for instance, increasing stability, bioactive liposome conjugates, and targeted drug, gene, and image agent delivery. In this study, novel targeted lipopolymers, peptide 18/peptide 563-poly(2-ethyl-2-oxazoline)-dioleoylphosphatidyl-ethanolamine (P18/P563-PEtOx-DOPE), have been demonstrated to be successfully synthesized. The structures of P18/P563-PEtOx-DOPE were confirmed by FT-IR spectroscopy, GPC, and 1H-NMR. In this strategy, poly(2-ethyl 2-oxazoline)-modified liposomes were firstly constructed with molecular weights of 3,500 and 5,800 Da. Then, we chose PEtOx5800-DOPE because it has been obtained better particle size (88.74 ± 0.6816) according to the DLS results. Then, peptides- and dye-PEtOx lipid-based nanovesicle (LN) were prepared by peptide-18, peptide-563, and 7-mercapto-4-methyl coumarin. Genetic material (pDNA) was encapsulated into the liposomes and evaluated the encapsulation of plasmid DNA with migration by using agarose gel electrophoresis. In vitro cytotoxicity experiment results on prostate cancer and breast cancer cell lines, parallelly with the healthy prostate (PNT1A) and breast (MCF10A) epithelial cell lines, cells showed insignificant toxic effects. Thus, we can suggest a novel PEtOx phospholipid thanks to this article and its integration with ligands, which great potential for gene transfer system. [ABSTRACT FROM AUTHOR]

Purpose: Zoledronic acid (ZA) is one of the drugs used clinically for the treatment of osteoporosis, and its therapeutic effect is due to the inhibition of osteoclastic cells leading to bone resorption. The aim of this study is developing an optimization method for poly(lactide-co-glycolide) (PLGA) nanoparticles of ZA which is intended for local application to enable guided bone regeneration. Methods: Three formulation parameters (ZA content, PLGA/Pluronic F68 ratio, and organic to aqueous phase ratio) were optimized to evaluate their effects on particle size (Y1), polydispersity index (PDI) (Y2), zeta potential (Y3), and entrapment efficiency (Y4) utilizing central composite experimental design (CCD). Interaction among components was studied by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction analysis. Morphology of nanoparticles was visualized with transmission electron microscopy (TEM). Stability studies of nanoparticles were also carried out for 6 months. Results: The results revealed that formulation parameters significantly affected Y1, Y2, Y3, and Y4 of the nanoparticles. The developed quadratic model showed high correlation (R2 > 0.84) between predicted response and evaluated parameters. Spherical nanoparticles with low mean particle size (< 106.0 nm) and high encapsulation efficiency (> 39.54%) were obtained with the optimized nanoparticle formulation and maintained colloidal stability for 6 months. Conclusions: The use of CCD for the optimization of ZA-loaded PLGA nanoparticles has provided accessibility to the formulation with optimum properties with less experimental procedure and therefore presents an important model for predicting the properties of nanoparticles prepared with PLGA polymer commonly used in the field of drug delivery. [ABSTRACT FROM AUTHOR]

Studies on preparation of in situ gel formulations containing diphtheria toxoid as the model active substance and their intranasal administration have been conducted in this study. The objective of mucosal vaccination is to stimulate both systemic and mucosal immune responses. In situ gel formulations were prepared by using, in different ratios, mixtures of Poloxamer 407 and Poloxamer 188 polymers, which gelate in a temperature-dependent manner, and mucoadhesive polymers carbopol 934, hydroxypropyl methyl cellulose, hydroxypropyl cellulose or chitosan. Following pre-formulation studies, F1, F2, F3, F4, F5, F6 and F7 formulations, which gelate at intervals and temperatures in accordance with nasal temperatures, were subjected to more comprehensive studies. For this purpose, organoleptic characteristics of the formulations were identified, their pH and mucoadhesive potencies were measured and rheological behaviors were characterized. Calculated amounts of diphtheria toxoid were added to formulations after optimization of formulations was achieved, and assay and in vitro release studies were carried out. Formulations coded F3 and F7 were considered to be superior to other formulations given the in vitro test results. Therefore, these formulations were tested in guinea pigs to determine immune responses, which they would produce following intranasal and subcutaneous administration. Absorbance values of ELISA tests and antibody neutralization test showed that formulations coded F3 and F7 were unable to stimulate adequate systemic immune response when either of the formulations was administered alone intranasally, whereas F7 resulted in significantly increased neutralizing antibody titers with intranasal administration as a booster dose following subcutaneous administration. [ABSTRACT FROM AUTHOR]

An ideal gene carrier is required both in safety and efficiency for transfection. We examined the use of water soluble chitosan and polyethyleneimine as a carrier for anti-angiogenic protein, TSP-1 coded, in gene delivery. The aim of this study was to synthesize and characterize polyethylene glycol conjugated cationic polymers to increase anti-angiogenic gene transfection and reduce possible cytotoxicity. Gel electrophoresis study showed strong DNA binding ability of modified cationic polymers. Also structural properties of pegylated polymers were confirmed by (1)H-NMR. We investigated in vitro properties of PEG conjugated and coated particles which were observed between 145 and 250 nm with the positive zeta potential value. In addition, the chitosan-based DNA complexes did not induce remarkable cytotoxicity against MCF-7 cells. Due to low cytotoxicity, we observed high transfection efficiency at chitosan-based formulations compared with PEI ones. Although transfection studies carried on in vitro conditions, we measured slight increases at transfection with PEGylation. PEG-conjugated chitosan formulations can be a promising candidate due to its efficiency in condensing and transfection of pDNA, its low cytotoxicty and comparatively high encapsulation degree., (Copyright © 2012 Wiley Periodicals, Inc.)

This study describes an orthogonal experimental design to optimize the formulation of 5-fluorouracil (5-FU) loaded poly D,L (lactide-co-glycolide) (PLGA) nanoparticles (5FU-NP) by a nanoprecipitation-solvent displacement technique. The type of surfactant, amount of acetone and molecular weight of the polymer with three levels of each factor were selected and arranged in an L18(3(5)) orthogonal experimental table. From the statistical analysis of the data polynominal equations were generated. Optimized formulations have the particle size ranging from 160 to 250 nm. Smallest nanoparticles (161+/-1.22 nm) were obtained using Resomer PLGA 755 and pluronic F-68 with 10 ml acetone amount. Under these conditions the 5-FU entrapment percentage was maximum 78.30%, suggesting 5-FU might be entrapped and adsorbed on the nanoparticle surface. In vitro release of three formulations with maximum drug entrapment efficiency and minimum particle size, were also investigated by release kinetics. According to the determined coefficients, release data fit to Higuchi's diffusion kinetics. The in vitro release of 5FU-NP in phosphate buffered saline (PBS, pH 7.4) is suggested to be controlled by a combination of diffusion with slow and gradual erosion of the particles. Also, the antimicrobial activity was observed even on the end of seventh day with all formulations.