Fixed-point "blasting" triggered by second near-infrared window light for augmented interventional photothermal therapy.

One of the major limitations of current cancer therapy is the inability to destroy tumors with high efficacy and minimal invasiveness. Herein, we developed a proof-of-concept fixed-point "blasting" strategy to destroy the "castle" of tumors and realized efficient interventional photothermal therapy. The "blasting" materials were composed of photothermal nanoparticles (ancient ink nanoparticles, AINP) and a low boiling point phase change agent (perfluoromethylcyclopentane, FMCP). An injectable in situ-forming thermal-responsive hydrogel composed of biodegradable and biocompatible polymers was employed as a carrier to load the AINP and FMCP. The obtained hydrogel system was a flowable aqueous solution at low or room temperature for facile injection; meanwhile, once administered, it rapidly transformed into a fixed gel at a body temperature of about 37 °C. This unique property could effectually fix the AINP and FMCP and thus restrict the destruction region inside the tumor. Subsequently, triggered by second window near-infrared light, the solid tumors were effectively destroyed by a mild photothermal effect and the subsequent gas mechanical damage. We envisage that this fixed-point "blasting" strategy will pave a new way for the next generation of cancer-interventional photothermal therapy.

Synthesis and evaluation of polymeric micelle containing piperacillin/tazobactam for enhanced antibacterial activity.

Infections caused by multidrug-resistant bacteria such as P. aeruginosa are important therapeutic complications. Piperacillin/Tazobactam is considered a safe antimicrobial agent. But we should not ignore the prevalence of resistant strains to this drug. In this work, a new polymeric micelle composed of Piperacillin/Tazobactam-loaded Poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PLGA-PEG) was developed to improve the antimicrobial performance of P/T. The SEM and TEM studies of PLGA-PEG micelle showed, semi-spherical morphology with a mean diameter of below 30 nm. Zeta potential results indicated that the surface charge of PLGA-PEG micelle was -2.98 mV, while after encapsulation of P/T, the surface charge decreases to -4.13 mV. Clinical strains of P. aeruginosa were isolated and their resistance pattern against different antibiotics was evaluated. The MIC of free and P/T -Loaded PLGA-PEG micelles was determined. Also, the effect of free or P/T micelle against minimal biofilm eradication concentration and motility inhibition was evaluated. The bacterial isolates were resistant to most common antibiotics. The MIC of the free drug form and micelle form ranged from 4 to 512 µg/ml and 2 to 256 µg/ml, respectively. Generally, micelle showed more effective antibiofilm activities, inhibition of bacterial motility and reducing the MIC than that free drug form.

The Effect of the Thermosensitive Biodegradable PLGA⁻PEG⁻PLGA Copolymer on the Rheological, Structural and Mechanical Properties of Thixotropic Self-Hardening Tricalcium Phosphate Cement.

The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation with the evolution of the setting reaction. The study proposes that it is possible to improve and tune the properties of CPCs via the addition of a thermosensitive, biodegradable, thixotropic copolymer based on poly(lactic acid), poly(glycolic acid) and poly(ethylene glycol) (PLGA⁻PEG⁻PLGA) which undergoes gelation under physiological conditions. The setting times of alpha-tricalcium phosphate (α-TCP) mixed with aqueous solutions of PLGA⁻PEG⁻PLGA determined by means of time-sweep curves revealed a lag phase during the dissolution of the α-TCP particles. The magnitude of the storage modulus at lag phase depends on the liquid to powder ratio, the copolymer concentration and temperature. A sharp increase in the storage modulus was observed at the time of the precipitation of calcium deficient hydroxyapatite (CDHA) crystals, representing the loss of paste workability. The PLGA⁻PEG⁻PLGA copolymer demonstrates the desired pseudoplastic rheological behaviour with a small decrease in shear stress and the rapid recovery of the viscous state once the shear is removed, thus preventing CPC phase separation and providing good cohesion. Preliminary cytocompatibility tests performed on human mesenchymal stem cells proved the suitability of the novel copolymer/α-TCP for the purposes of mini-invasive surgery.

Synthesis of multifunctional Fe3O4@PLGA-PEG nano-niosomes as a targeting carrier for treatment of cervical cancer.

A new folic acid (FA)-conjugated poly (lactic-co-glycolicacid) (PLGA)-polyethylene glycol (PEG) nano-noisome was prepared. The noisome was employed as a drug delivery system to load curcumin (Cur) as a model drug and fluorescent probe for cervical cancer therapy and cell imaging. The Fe3O4@PLGA-PEG@FA noisomes were prepared through facile emulsion solvent evaporation and conjugation chemistry method, possessing the properties of high rapid magnetic separation and targeting character. X-ray photoelectron spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), thermogravimetric analysis (TGA), and vibrating sample magnetometer (VSM) were adopted to characterize the chemical structure and properties of these niosomes. MTT assay revealed that the blank noisomes exhibited excellent biocompatibility. The in vitro drug loading and release behavior studier showed the as prepared nano-noisome presented ultrahigh performance as drug carrier. The confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) experiments demonstrated that Cur-loaded Fe3O4@PLGA-PEG@FA niosomes achieved significantly high targeting efficiency for cervical cancer. Additionally, the FA-targeted niosomes exhibited higher antitumor efficiency than free Cur. Cell morphology, the mitochondrial membrane potential and cell cycle changes indicated that Cur-loaded niosomes induced HeLa229 cells to apoptosis by destroying mitochondrion of cervical tumor cells, simultaneously changing nuclear morphology and blocking tumor cell proliferation. These results demonstrate that Fe3O4@PLGA-PEG@FA noisomes have promising applications as targeted drug delivery system for sustained drug release in cancer treatment.

Development of poly(lactide-co-glycolide) nanoparticles functionalized with a mitochondria penetrating peptide.

The development of mitochondria-targeting cell permeable vectors represents a promising therapeutic approach for several diseases, such as cancer and oxidative pathologies. Nevertheless, access to mitochondria can be difficult. A new hybrid material composed by poly(lactide-co-glycolide) (PLGA) functionalized with a 6-mer mitochondria penetrating peptide (MPP), consisting in alternating arginine and unnatural cyclohexylalanine, was developed. Circular dichroism, FT-IR and DSC studies indicated that the conjugation of the peptide with the polymer led to the obtainment of a more rigid material with respect to both PLGA and MPP as such. In particular, a conformational rearrangement to a helical structure was observed for MPP. MPP-PLGA conjugates were used for the preparation of nanoparticles that showed no cytotoxicity in MTT assay, suggesting their putative use for future studies on mitochondria targeting. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Mesoscale nanoparticles selectively target the renal proximal tubule epithelium.

We synthesized "mesoscale" nanoparticles, approximately 400 nm in diameter, which unexpectedly localized selectively in renal proximal tubules and up to 7 times more efficiently in the kidney than other organs. Although nanoparticles typically localize in the liver and spleen, modulating their size and opsonization potential allowed for stable targeting of the kidneys through a new proposed uptake mechanism. Applying this kidney targeting strategy, we anticipate use in the treatment of renal disease and the study of renal physiology.

Aspartic acid-based modified PLGA-PEG nanoparticles for bone targeting: in vitro and in vivo evaluation.

Nanoparticles (NP) that target bone tissue were developed using PLGA-PEG (poly(lactic-co-glycolic acid)-polyethylene glycol) diblock copolymers and bone-targeting moieties based on aspartic acid, (Asp)(n(1,3)). These NP are expected to enable the transport of hydrophobic drugs. The molecular structures were examined by (1)H NMR or identified using mass spectrometry and Fourier transform infrared (FT-IR) spectra. The NP were prepared using the water miscible solvent displacement method, and their size characteristics were evaluated using transmission electron microscopy (TEM) and dynamic light scattering. The bone targeting potential of the NP was evaluated in vitro using hydroxyapatite affinity assays and in vivo using fluorescent imaging in zebrafish and rats. It was confirmed that the average particle size of the NP was <200 nm and that the dendritic Asp3 moiety of the PLGA-PEG-Asp3 NP exhibited the best apatite mineral binding ability. Preliminary findings in vivo bone affinity assays in zebrafish and rats indicated that the PLGA-PEG-ASP3 NP may display increased bone-targeting efficiency compared with other PLGA-PEG-based NP that lack a dendritic Asp3 moiety. These NP may act as a delivery system for hydrophobic drugs, warranting further evaluation of the treatment of bone disease.

Marked effects of combined TPGS and PVA emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles: in vitro and in vivo evaluation.

The purpose of this study was to investigate the effect of d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) alone or in combination with other emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles for in vivo applications. Nanoparticles were prepared by nanoprecipitation or single-emulsion solvent evaporation method using TPGS alone or in combination with other surfactants. These nanoparticles were fully characterized by different techniques. For nanoprecipitation preparations, by adding 0.1% TPGS to polyvinyl alcohol in the aqueous phase, encapsulation efficiency markedly increased (up to 82%); moreover, drug release was readily controlled up to 3 days. Regarding emulsion solvent evaporation method, the highest encapsulation efficiency was obtained for nanoparticles emulsified with polyvinyl alcohol or TPGS; however, the burst release was high. When the combination of TPGS and polyvinyl alcohol was applied a marked increase in encapsulation efficiency (∼ 90%) was observed and the drug release was extended to more than one week. Pharmacokinetic measurements showed that the optimum formulation generated 14.4 times higher AUC and lasted 5.1 times longer when compared to free drug. Overall, using TPGS in combination with polyvinyl alcohol as an emulsifier in preparing etoposide loaded PLGA-PEG nanoparticles markedly increased the encapsulation efficiency, sustained drug release and resulted in nanoparticles with noticeable sustainable in vivo disposition.

Thermo- and pH-responsive copolymers based on PLGA-PEG-PLGA and poly(L-histidine): synthesis and in vitro characterization of copolymer micelles.

A series of novel thermo- and pH-responsive block copolymers of PHis-PLGA-PEG-PLGA-PHis composed of poly(ethylene glycol) (PEG), poly(D,L-lactide-co-glycolide) (PLGA) and poly(L-histidine) (PHis) were synthesized and used for the construction of stimuli-responsive copolymer micelles. The starting polymers of PLGA-PEG-PLGA and PHis were synthesized by ring-opening polymerization of dl-lactide and glycolide with PEG as an initiator and L-histidine N-carboxylanhydride with isopropylamine as an initiator, respectively. The final copolymer was obtained by the coupling reaction of PHis with PLGA-PEG-PLGA. The copolymer micelles were constructed to have an inner core consisting of two hydrophobic blocks (PLGA and deprotonated PHis) and an outer hydrophilic PEG shell. The temperature- and pH-induced structure changes of the micelles were characterized by an alteration in particle size, a decrease in pyrene fluorescence intensity, and a variation of (1)H NMR spectra in D2O. It was speculated that the hydrophobic-hydrophilic transitions of PEG and PHis in response to temperature and pH variations accounted for the destabilization of micelles. In vitro release profiles, cell cytotoxicity and intracellular location studies further confirmed the temperature- and pH-responsive properties of the copolymer micelles. These results demonstrate the potential of the developed copolymers to be stimuli-responsive carriers for targeted delivery of anti-cancer drugs.

Poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) thermogel as a novel submucosal cushion for endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is a clinical therapy for early stage neoplastic lesions in the gastrointestinal tract. It is, however, faced with a crucial problem: the high occurrence of perforation. The formation of a submucosal fluid cushion (SFC) via a fluid injection is the best way to avoid perforation, and thus an appropriate biomaterial is vital for this minimally invasive endoscopic technique. In this study, we introduced an injectable thermogel as a novel submucosal injection substance in ESD. The hydrogel synthesized by us was composed of poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers. The polymer/water system was a low-viscosity fluid at room temperature and thus easily injected, and turned into a non-flowing gel at body temperature after injection. The submucosal injection of the thermogel to create SFCs was performed in both resected porcine stomachs and living minipigs. High mucosal elevation with a clear margin was maintained for a long duration. Accurate en bloc resection was achieved with the assistance of the thermogel. The mean procedure time was strikingly reduced. Meanwhile, no obvious bleeding, perforation and tissue damage were observed. The application of the thermogel not only facilitated the ESD procedure, but also increased the efficacy and safety of ESD. Therefore, the PLGA-PEG-PLGA thermogel provides an excellent submucosal injection system, and has great potential to improve the ESD technique significantly.

Polymeric topology and composition constrained polyether-polyester micelles for directional antitumor drug delivery.

Amphiphilic linear and dumbbell-shaped poly(ethylene glycol)-poly(lactide-co-glycolide) (PEG-PLGA) copolymers were simply synthesized by the ring-opening polymerization of lactide and glycolide using PEG or tetrahydroxyl-functionalized PEG as the macroinitiator and stannous octoate as the catalyst. The copolymers spontaneously self-assembled into spherical micelles in phosphate-buffered saline at pH 7.4. The self-assembly behavior was dependent on both the polymeric topology and composition. Doxorubicin (DOX), an anthracycline antitumor drug, was loaded into micelles through nanoprecipitation. The in vitro release behavior could be adjusted by regulating the topology or composition of the copolymer, or the pH of the release medium. The effective intracellular DOX release from DOX-loaded micelles was confirmed by confocal laser scanning microscopy and flow cytometry in vitro. DOX-loaded micelles displayed great cellular proliferation inhibition efficacies after incubation for 24, 48 or 72 h. The hemolysis ratio of DOX was significantly reduced by the presence of copolymer. These properties indicated that the micelles derived from linear or dumbbell-shaped copolymers were promising candidates as smart antitumor drug carriers for malignancy therapy.

Isoniazid loaded core shell nanoparticles derived from PLGA-PEG-PLGA tri-block copolymers: in vitro and in vivo drug release.

A series of biodegradable low molecular weight PLGA-PEG-PLGA tri-block copolymers have been synthesized in powder form. The anti-tuberculosis drug Isoniazid (INH) loaded polymeric core-shell nanoparticles (CSNPs) have been prepared by sonication followed by water-in-oil-in-water (w/o/w) double emulsification technique. The nanoparticles (NPs) have been characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD) and X-ray photo electron spectroscopic (XPS) techniques. The drug loaded CSNPs were found to be 150-400 nm in size with spherical shape. The drug loading efficiency and drug content of the polymer NPs were determined by UV-vis spectrophotometry. The drug loading efficiency and drug content of the NPs were (12.8-18.67%) and (6.4-8.9%) respectively. The in vitro release behavior of the polymer NPs has been investigated by UV-vis spectrophotometry and the release kinetics mechanism has been evaluated by Korsemeyer-Peppas (KP) and Higuchi models. The in vitro release studies show initial burst release followed by controlled and uniform release for longer duration. The pharmacokinetic studies show that the INH bioavailability of INH loaded CSNPs is 28 fold higher than that of free INH and also the CSNPs show sustained drug release for longer duration.

Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics.

Mitochondrial dysfunctions cause numerous human disorders. A platform technology based on biodegradable polymers for carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in treating mitochondrial diseases. Here we report a rationally designed mitochondria-targeted polymeric nanoparticle (NP) system and its optimization for efficient delivery of various mitochondria-acting therapeutics by blending a targeted poly(d,l-lactic-co-glycolic acid)-block (PLGA-b)-poly(ethylene glycol) (PEG)-triphenylphosphonium (TPP) polymer (PLGA-b-PEG-TPP) with either nontargeted PLGA-b-PEG-OH or PLGA-COOH. An optimized formulation was identified through in vitro screening of a library of charge- and size-varied NPs, and mitochondrial uptake was studied by qualitative and quantitative investigations of cytosolic and mitochondrial fractions of cells treated with blended NPs composed of PLGA-b-PEG-TPP and a triblock copolymer containing a fluorescent quantum dot, PLGA-b-PEG-QD. The versatility of this platform was demonstrated by studying various mitochondria-acting therapeutics for different applications, including the mitochondria-targeting chemotherapeutics lonidamine and α-tocopheryl succinate for cancer, the mitochondrial antioxidant curcumin for Alzheimer's disease, and the mitochondrial uncoupler 2,4-dinitrophenol for obesity. These biomolecules were loaded into blended NPs with high loading efficiencies. Considering efficacy, the targeted PLGA-b-PEG-TPP NP provides a remarkable improvement in the drug therapeutic index for cancer, Alzheimer's disease, and obesity compared with the nontargeted construct or the therapeutics in their free form. This work represents the potential of a single, programmable NP platform for the diagnosis and targeted delivery of therapeutics for mitochondrial dysfunction-related diseases.

Preparation and investigation of sustained drug delivery systems using an injectable, thermosensitive, in situ forming hydrogel composed of PLGA-PEG-PLGA.

In situ gelling systems are very attractive for pharmaceutical applications due to their biodegradability and simple manufacturing processes. The synthesis and characterization of thermosensitive poly(D,L-lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymers as in situ gelling matrices were investigated in this study as a drug delivery system. Ring-opening polymerization using microwave irradiation was utilized as a novel technique, and the results were compared with those using a conventional method of polymerization. The phase transition temperature and the critical micelle concentration (CMC) of the copolymer solutions were determined by differential scanning calorimetry and spectrophotometry, respectively. The size of the micelles was determined with a light scattering method. In vitro drug release studies were carried out using naltrexone hydrochloride and vitamin B12 as model drugs. The rate and yield of the copolymerization process via microwave irradiation were higher than those of the conventional method. The copolymer structure and concentration played critical roles in controlling the sol-gel transition temperature, the CMC, and the size of the nanomicelles in the copolymer solutions. The rate of drug release could be modulated by the molecular weight of the drugs, the concentration of the copolymers, and their structures in the formulations. The amount of release versus time followed zero-order release kinetics for vitamin B12 over 25 days, in contrast to the Higuchi modeling for naltrexone hydrochloride over a period of 17 days. In conclusion, PLGA-PEG1500-PLGA with a lactide-to-glycolide ratio of 5:1 is an ideal system for the long-acting, controlled release of naltrexone hydrochloride and vitamin B12.

Paclitaxel and iron oxide loaded multifunctional nanoparticles for chemotherapy, fluorescence properties, and magnetic resonance imaging.

The multifunctional nanoparticles constructed from triphenylamine-poly(lactide-co-glycolide)-poly(ethyleneglycol)-poly(lactide-co-glycolide) (TPA-PEP) and folate-poly(2-ethyl-2oxazoline)-poly(D,L-lactide) (folate-PEOz-PLA) were developed in this study. Iron oxide nanoparticles (IOP) and paclitaxel (PTX) were coencapsulated in the nanoparticles with diameter less than 200 nm. The drug-loaded nanoparticles emit fluorescence peak at 460 nm when excited with wavelength of 350 nm. The in vitro antitumor activity of the drug-loaded nanoparticles was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays against HeLa cells. When the cells were exposed to the nanoparticles with different levels of folate but the same drug loading, cell viability decreases as the level of folate increases. Confocal laser scanning microscopy (CLSM) analysis shows that cellular uptake is lower for the non-folate-nanoparticles than that for the folate-nanoparticles. The in vitro and in vivo magnetic resonance imaging (MRI) studies indicate the better T2-Weighted images can be obtained for the folate-nanoparticles. In the anticancer effect evaluation, tumor-bearing mice administered with the 30%-folate-nanoparticles showed ~50% reduction in tumor volume after 23 days. The multifunctional nanoparticles as drug carrier with capabilities of both tumor-targeting and MRI present a new direction in drug delivery system development.

N-Boc-histidine-capped PLGA-PEG-PLGA as a smart polymer for drug delivery sensitive to tumor extracellular pH.

A pH-sensitive polymer was synthesized by introducing the N-Boc-histidine to the ends of a PLGA-PEG-PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N-Boc-histidine-capped PLGA-PEG-PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un-capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA-MB-435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N-Boc-histidine capped PLGA-PEG-PLGA might be a promising material for tumor targeting.

PLGA-PEG-PLGA hydrogel for ocular drug delivery of dexamethasone acetate.

AIM: This study aims to investigate the suitability of thermosensitive triblock polymer poly-(DL-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA as a matrix material for ocular delivery of dexamethasone acetate (DXA). METHODS: The copolymer was synthesized and evaluated for its thermosensitive and gelation properties. DXA in situ gel-forming solution based on PLGA-PEG-PLGA copolymer of 20% (w/w) was prepared and evaluated for ocular pharmacokinetics in rabbit according to the microdialysis method, which was compared to the normal eye drop. RESULT: The copolymer with 20% (w/w) had a low critical solution temperature of 32 degrees C, which is close to the surface temperature of the eye. The C(max) of DXA in the anterior chamber for the PLGA-PEG-PLGA solution was 125.2 microg/mL, which is sevenfold higher than that of the eye drop, along with greater area under the concentration-time curves (AUC). CONCLUSION: These results suggest that the PLGA-PEG-PLGA copolymer is potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bioavailability, efficacy of some eye drugs.

Polymeric nanoparticles for drug delivery.

The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Concurrently, targeted delivery technologies are becoming increasingly important as a scientific area of investigation. In cancer, targeted polymeric NPs can be used to deliver chemotherapies to tumor cells with greater efficacy and reduced cytotoxicity on peripheral healthy tissues. In this chapter, we describe the methods of (1) preparation and characterization of drug-encapsulated polymeric NPs formulated with biocompatible and biodegradable poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-b-PEG) copolymers; (2) surface functionalization of the polymeric NPs with the A10 2'-fluoropyrimidine ribonucleic acid (RNA) aptamers that recognize the prostate-specific membrane antigen (PSMA) on prostate cancer cells; and (3) evaluation of the binding properties of these targeted polymeric NPs to PSMA-expressing prostate cancer cells in vitro and in vivo. These methods may contribute to the development of other useful polymeric NPs to deliver a spectrum of chemotherapeutic, diagnostic, and imaging agents for various applications.

Polymeric nanoparticles for sustained down-regulation of annexin A2 inhibit prostate tumor growth.

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer related death in Western men. In prostate intraepithelial neoplasia annexin A2 expression is absent however upon loss of androgen dependence annexin A2 is subsequently over-expressed. Regaining regulatory control of annexin A2 presents a means of therapy in the treatment of hormone refractory prostate cancers. In an effort to regain control of aberrant annexin A2 expression we have formulated poly lactide-co-glycolide (PLGA) nanoparticles loaded with pDrive-sh AnxA2 plasmid DNA. These nanoparticles are capable of sustained intracellular delivery of pDrive-sh AnxA2 plasmid DNA vector for long-term siRNA mediated down-regulation of annexin A2. Intra-tumoral administration of pDrive-sh AnxA2 loaded nanoparticles to xenograft prostate tumors in nude mice demonstrates an overall decrease in tumor growth. The decrease in tumor growth is through a reduction of annexin A2 and VEGF mRNA and protein levels within the tumor mass. Administration of blank nanoparticles demonstrated no alteration in tumor growth or annexin A2 and VEGF at either the mRNA or protein levels. Our findings suggest that the use of sustained-release polymeric nanoparticles for down-regulation of annexin A2 expression may serve as an effective adjuvant treatment option for prostate cancer.

Metronidazole-loaded bioabsorbable films as local antibacterial treatment of infected periodontal pockets.

BACKGROUND: Periodontal disease is infectious in nature and leads to an inflammatory response. It arises from the accumulation of subgingival bacterial plaque and leads to the loss of attachment, increased probing depth, and bone loss. It is one of the world's most prevalent chronic diseases. In this study we developed and studied metronidazole-loaded 50/50 poly(DL-lactide-co-glycolide) (PDLGA), 75/25 PDLGA, and poly(DL-lactic acid) (PDLLA) films. These films are designed to be inserted into the periodontal pocket and treat infections with controlled-release metronidazole for >or=1 month. METHODS: The structured films were prepared using the solution-casting technique. Concentrated solutions and high solvent-evaporation rates were used to get most of the drug located in the bulk, i.e., in whole film's volume. The effects of copolymer composition and drug content on the release profile, cell growth, and bacterial inhibition were investigated. RESULTS: The PDLLA and 75/25 PDLGA films generally exhibited a low- or medium-burst release followed by a moderate release at an approximately constant rate, whereas the 50/50 PDLGA films exhibited a biphasic release profile. The drug released from films loaded with 10% weight/weight metronidazole resulted in a significant decrease in bacterial viability within several days. When exposed to human gingival fibroblasts in cell culture conditions, these films maintained their normal fibroblastic features. CONCLUSIONS: This study enabled the understanding of metronidazole-release kinetics from bioabsorbable polymeric films. The developed systems demonstrated good biocompatibility and the ability to inhibit Bacteroides fragilis growth; therefore, they may be useful in the treatment of periodontal diseases.