Drug Release Profile Of Nanoparticles Research Articles

Assessment of mechanism involved in the apoptotic and anti-cancer activity of Quercetin and Quercetin-loaded chitosan nanoparticles.

In prior studies, Quercetin was revealed to exhibit anti-cancer features in a variety of cancer cell lines. However, the impact of Quercetin on neuroblastoma is unknown. This study looked into the potential cytotoxic effects of Quercetin and Quercetin-loaded chitosan nanoparticles (NPs) on the SH-SY5Y cell line. In this study, NPs containing Quercetin was prepared and characterization studies were performed. The vitality of the cells was measured using the XTT test after 24h of treatment with various concentrations of Quercetin (0.5, 1, 2, 4, and 8µg/mL). ELISA kits were used to detect the amounts of cleaved PARP, BCL-2, 8-Hydroxy-deoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant status, and total antioxidant status in the cells. The results of the chitosan NPs characterization investigation revealed that the particle size, encapsulation effectiveness, and drug release profile of NPs were all appropriate for cell culture studies. Quercetin and Quercetin-loaded chitosan NPs significantly reduced cell viability in SH-SY5Y cells at different concentrations (**p < 0.05). 2µg/mL Quercetin and Quercetin-loaded chitosan NPs significantly enhanced the levels of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP, and total oxidant in ELISA testing. However, treatment with 2µg/mL of Quercetin and Quercetin-loaded chitosan NPs did not affect the amount of BCL-2 protein. Overall, Quercetin and Quercetin-loaded chitosan NPs caused significant cytotoxicity in SH-SY5Y cells via producing oxidative stress, DNA damage, and eventually apoptosis.

Preparation of Silymarin–quercetin Loaded Nanoparticles by Spontaneous Emulsification Solvent Diffusion Method Using D-alpha-tocopheryl Poly (Ethylene Glycol) 1000 Succinate

Silymarin, a flavonolignan, derived from Silybum marianum, family Asteraceae has long been used as a hepatoprotective remedy. Silymarin has cytoprotective activities due to its antioxidant property and free radical scavenging activity. The pharmacokinetic studies of past three decades revealed that silymarin has poor absorption, rapid metabolism especially by Phase II metabolism and ultimately poor oral bioavailability. Quercetin, a flavonoid present in edible vegetables and fruits, It is a potent antioxidant and shows a wide range of biological functions. Quercetin improves blood levels and efficacy of number of drugs since it is P-Glycoprotein inhibitor and also inhibits drug metabolizing enzymes. Both silymarin and quercetin were, poorly soluble in the water shows low bioavailability. The advanced type of formulation like polymeric nanoparticles (PNPs) can be successfully utilised for bioavailability enhancement and targeting the Silymarin-quercetin to hepatocytes. A controlled release PNPs of silymarin-quercetin were prepared by spontaneous emulsification solvent diffusion (SESD) method using Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable polymer, D-alpha-tocopheryl poly (ethylene glycol) 1000 succinate (TPGS) used as a solubilizer, as an emulsifier. TPGS as an emulsifier and further as a matrix material blended with PLGA was used to enhance the encapsulation efficiency and improve the drug release profile of nanoparticles. Different formulations with various drug: polymer ratios and volume and concentration of surfactant, centrifugation time were evaluated. The effect of formulation parameters such as drug/polymer ratio, volume and surfactant content were evaluated. The surface morphology and size of the nanoparticles were studied by scanning electron microscopy (SEM) Transmission electron microscopy (TEM). Drug encapsulation efficiency and in vitro drug release profiles of nanoparticles were determined using UV spectrophotometry. The nanoparticles prepared with combination of both the drugs in this study were spherical with size range of 100–200 nm. It was shown that TPGS was a good emulsifier for producing nanoparticles of hydrophobic drugs and improving the encapsulation efficiency and drug loading and drug release profile of nanoparticles. Although the amount of the TPGS used had a significant effect on the nanoparticle size and morphology, the drug loading and release profile of nanoparticles

Preparation of curcumin-poly (allyl amine) hydrochloride based nanocapsules: Piperine in nanocapsules accelerates encapsulation and release of curcumin and effectiveness against colon cancer cells.

Curcumin (CUR) is a natural polyphenol present in the rhizomes of Curcuma longa and possesses diverse pharmacological effects, especially anti-carcinogenic effects against several types of cancers. Unfortunately, this novel compound has poor aqueous solubility and bioavailability that limit its pharmaceutical effects. The use of polymeric nanocapsules has been applied in order to overcome such problems. Thus, our present study aimed at developing two novel polymeric nanoparticles (NPs) systems that encapsulate either curcumin alone (CURN) or with piperine (CURPN), which acts as a glucuronidation inhibitor and increases the bioavailability of CUR. The NPs were successfully designed by self-assembled nanoprecipitation method and their characteristics were identified by Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and Zeta potential analysis. The drug release profiles of NPs were monitored under different pH, and their cytotoxic effects were assessed in vitro against Caco-2 cells and in vivo against dimethylhydrazine-induced colon cancer in mice. The FTIR and XRD analyses and SEM images showed amorphous and spherical shaped CURN and CURPN of 80-100nm sized diameter. In vitro drug release study showed that pH triggered the maximum release of CUR in basic medium compared to acidic and neutral media, and following Higuchi model. CUR nanoencapsulation enhanced its physiochemical properties and drug loading and release. In vitro and in vivo studies showed that CUR NPs exerted selective and potential cytotoxic effects against colon cancer cells. The addition of piperine facilitated the encapsulation and drug loading of CUR. Thus, CUR nanoencapsulation enhanced the solubility and bioavailability of curcumin rendering it more effective against colon cancer.

Development of implantable hydroxypropyl-β-cyclodextrin coated polycaprolactone nanoparticles for the controlled delivery of docetaxel to solid tumors

Treatment of cancer is one of the most challenging problems and conventional therapies are inadequate for targeted, effective and safe therapy. Development of nanoparticle-based drug delivery systems emerge as promising carriers in this field to ensure delivery of anticancer drug to tumor site. The aim of this study was to design hydroxypropyl-β-cyclodextrin (CD) coated nanoparticles using poly(e-caprolactone) (PCL) and its derivative poly(ethylene glycol)-block-poly(e-caprolactone) (mePEG-PCL) to be applied as implants to tumor site following surgical operation in cancer patients. CD coated PCL and mePEG-PCL nanospheres were developed to encapsulate poorly soluble chemotherapeutic agent docetaxel (DOC) to improve solubility of drug and to enhance cellular penetration with longer residence time and higher local drug concentration. Nanospheres were prepared according to the nanoprecipitation method and coated with hydroxypropyl-β-cyclodextrin (Cavasol® W7HP). Cyclodextrin coating was performed for higher drug encapsulation and controlled but complete drug release from nanoparticles. Nanoparticle diameters varied between 60 and 136 nm depending on polymer used for preparation and coating. All nanoparticles have negative surface charge and zeta potential values varied between −22 and −37 mV. Encapsulation efficiency of formulations were found to be between 46 and 73 % and CD coated nanoparticles have significantly higher entrapment efficiency. Drug release profiles of nanoparticles were similar to each other and all formulations released encapsulated drug in approximately 12 h. Especially, CD-PCL nanoparticles were found to have highest entrapment efficiency and anticancer efficacy against MCF-7 human breast adenocarcinoma cell lines. Our study proved that polycaprolactone and its PEGylated derivatives can be suitable for development of implantable nanoparticles as a potential drug delivery system of DOC for cancer treatment and a good candidate for further in vivo studies.

Preparation and optimization of matrix metalloproteinase-1-loaded poly(lactide-co-glycolide-co-caprolactone) nanoparticles with rotatable central composite design and response surface methodology

Matrix metalloproteases are key regulatory molecules in the breakdown of extracellular matrix and in inflammatory processes. Matrix metalloproteinase-1 (MMP-1) can significantly enhance muscle regeneration by promoting the formation of myofibers and degenerating the fibrous tissue. Herein, we prepared novel MMP-1-loaded poly(lactide-co-glycolide-co-caprolactone) (PLGA-PCL) nanoparticles (NPs) capable of sustained release of MMP-1. We established quadratic equations as mathematical models and employed rotatable central composite design and response surface methodology to optimize the preparation procedure of the NPs. Then, characterization of the optimized NPs with respect to particle size distribution, particle morphology, drug encapsulation efficiency, MMP-1 activity assay and in vitro release of MMP-1 from NPs was carried out. The results of mathematical modeling show that the optimal conditions for the preparation of MMP-1-loaded NPs were as follows: 7 min for the duration time of homogenization, 4.5 krpm for the agitation speed of homogenization and 0.4 for the volume ratio of organic solvent phase to external aqueous phase. The entrapment efficiency and the average particle size of the NPs were 38.75 ± 4.74% and 322.7 ± 18.1 nm, respectively. Further scanning electron microscopy image shows that the NPs have a smooth and spherical surface, with mean particle size around 300 nm. The MMP-1 activity assay and in vitro drug release profile of NPs indicated that the bioactivity of the enzyme can be reserved where the encapsulation allows prolonged release of MMP-1 over 60 days. Taken together, we reported here novel PLGA-PCL NPs for sustained release of MMP-1, which may provide an ideal MMP-1 delivery approach for tissue reconstruction therapy.

Brimonidine Tartrate–Eudragit Long-Acting Nanoparticles: Formulation, Optimization, In Vitro and In Vivo Evaluation

In the present study, an effort was made to design prolonged release Eudragit nanoparticles of brimonidine tartrate by double emulsion-solvent evaporation technique for the treatment of open-angle glaucoma. The effect of various formulation variables like initial drug amount, lecithin proportion, phase volume and pH, secondary emulsifier and polymer proportion were studied. Various process variables like energy and duration of emulsification, lyophilization on the characteristics of nanoparticles and in vitro drug release profile were studied. The selected formulations were subjected to in vivo intraocular pressure-lowering efficacy studies by administering aqueous dispersion of nanoparticles into the lower cul de sac of glaucomatous rabbits. The prepared Eudragit-based nanoparticles were found to have narrow particle size range and improved drug loading. The investigated process and formulation variables found to have significant effect on the particle size, drug loading and entrapment efficiency, and in vitro drug release profile of nanoparticles. The selected formulations upon in vivo ocular irritability and tolerability tests were found to be well tolerated with no signs of irritation. In vivo pharmacodynamic efficacy studies revealed that the selected nanoparticle formulations significantly improved the therapy as area under the ∆IOP vs. time curve [AUC((∆IOP vs. t))] showed several fold increase in intensity and duration of intraocular pressure (IOP) decrease. All the selected nanoparticle formulations were found to prolong the drug release in vitro and prolong IOP reduction efficacy in vivo, thus rendering them as a potential carrier in developing improved drug delivery systems for the treatment of glaucoma.

Evaluation of dialysis membrane process for quantifying the in vitro drug-release from colloidal drug carriers

The reliability of in vitro drug-release profiles of colloidal drug carriers using the dialysis membrane process was evaluated with a drug-selective electrode that measures the concentration profile of procaine hydrochloride (PrHy) in solution. This method allows for the measurement of actual concentration of drugs released from colloidal drug carriers since it does not require the separation of carriers from free drug molecules. The diffusion rate of PrHy was shown to increase with increasing molecular weight cut-off (MWCO) of the dialysis membrane and concentration difference between the dialysis membrane and bulk solution. These two findings demonstrated potential problems in the determination of drug-release profile due to the difficulty in measuring actual drug release profile of nanoparticles. The PrHy release from poly( N-isopropylacrylamide) (PNIPAM) microgels was shown to last 6 min, but the release in a 10 kDa MWCO dialysis cassette shows a release lasting over 1 h. This suggests that the dialysis membrane process introduces error in the determination of rapid release kinetics of nanoparticles. We showed that a drug-selective electrode provides a more robust method for quantifying the release kinetics of hydrophilic drugs.

Preparation of PLGA nanoparticles using TPGS in the spontaneous emulsification solvent diffusion method

D-alpha-tocopheryl poly (ethylene glycol) 1000 succinate (TPGS) is a widely used form of vitamin E that has been used as a solubilizer, an emulsifier and as a vehicle for drug delivery formulations. In this study, poly lactide-co-glycolide (PLGA) nanoparticles were prepared by spontaneous emulsification solvent diffusion (SESD) method. TPGS as an emulsifier and further as a matrix material blended with PLGA was used to enhance the encapsulation efficiency and improve the drug release profile of nanoparticles. Rifampicin and estradiol valerate were used as model drugs with different water solubility. The effect of formulation parameters such as drug/polymer ratio, oil phase combination, volume and surfactant content was evaluated. The surface morphology and size of the nanoparticles were studied by scanning electron microscopy (SEM) and laser light scattering. Drug encapsulation efficiency and in vitro drug release profiles of nanoparticles were determined using high performance liquid chromatography (HPLC). The nanoparticles prepared in this study were spherical with size range of 150–250 nm. It was shown that TPGS was a good emulsifier for producing nanoparticles of hydrophobic drugs and improving the encapsulation efficiency and drug loading and drug release profile of nanoparticles. However, the drug loading efficiency of rifampicin, a slightly water-soluble molecule, was significantly lower than that of estradiol valerate, a water insoluble molecule.