Nanoparticles For Sustained Release Research Articles

Cell Line and Augument Cellular Uptake Study of Statistically Optimized Sustained Release Capecitabine Loaded Eudragit S100/PLGA(poly(lacticco- glycolic acid)) Nanoparticles for Colon Targeting.

Capecitabine, an anti cancer drug, has a very short drug elimination half-life (0.49 to 0.89 h). High doses and absence of targeting ability in the colon region may lead to more side effects to the patients with colon cancer. To develop and optimize sustained release nanoparticles for effective treatment of colon cancer. Eudragit S100-PLGA(poly (lactic-co-glycolic acid)) nanoparticles were prepared by a double emulsification, solvent evaporation method followed by high-pressure homogenisation evaluated and the particles were evaluated for surface morphology, particle size analysis, polydispersity index, drug content, % entrapment efficiency and in vitro drug release. To optimize the batch a 32 full factorial design was applied. The optimized batch was evaluated for cytotoxicity and cellular uptake study. The optimized formulation exhibited 179.25 nm mean particle size, 71.27% of drug entrapment efficiency and 81.824% drug release up to 72 h. When the concentration of capecitabine was increased from 50-500 μg/ml, the % cytotoxicity of nanoparticles and capecitabine (pure drug) increased from 8.5 to 97.70% and 2.7 to 82.23%, respectively. As per a cellular uptake study, the optimized nanoparticles were completely uptaken by HT 29 adenocarcinoma cells within 2 to 4 h. Optimized Eudragit S100-PLGA nanoparticles are a promising delivery system for colon targeting.

Poly (d, l-lactide-co-glycolide) nanoparticles for sustained release of tacrolimus in rabbit eyes

Tacrolimus (TAC)-loaded Ploy-lactide-co-glycolide nanoparticles (PLGA-NPs) was developed by emulsification-diffusion method for topical ocular delivery in certain ocular conditions where therapeutic level of immunomodulator into eyes is required for sufficient duration. So, we optimized TAC-loaded PLGA-NPs with higher TAC payload. The mean particle-size and its distribution, polydispersity, zeta-potentials, morphology, drug encapsulation and loading capacity of NPs were analyzed. Transcorneal permeation through excised rabbit cornea revealed instant and controlled permeation of TAC from TAC-aqueous suspension (TAC-AqS) and from PLGA-NPs, respectively. Stability study results indicated that there were no significant changes in above characteristics for 1-month storage at 25°C. The safety of PLAG was established by modified Draize’s test after its topical administration in rabbit eyes. The adopted liquid chromatography-electrospray ionization tandem mass spectrometry was successfully applied for TAC quantification in ocular tissues and aqueous-humor. PLGA-NPs improved corneal, conjunctival and aqueous humor bioavailability of TAC. A considerably higher TAC-concentration from F2 was found in ocular tissues even at 24h and in aqueous humor till 24h following its topical ocular administration as compared to TAC-AqS. The PLGA-NPs significantly enhanced ocular bioavailability of TAC than that of aqueous suspension.

Poly(lactic-co-glycolic acid) nanoparticles for sustained release of allyl isothiocyanate: characterization, in vitro release and biological activity

The objective of this study is to establish the ability of entrap allyl isothiocyanate (AITC) into polymeric nanoparticles to extend its shelf life and enhance its antiproliferative properties. Natural compounds, such as AITC, have showed multi-targeting activity resulting in a wide-range spectrum of therapeutic properties in chronic and degenerative diseases, conversely with most current pharmaceutical drugs showing single targeting activity and often result in drug resistance after extended administration periods. Apparently, AITC-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) reduced AITC degradation and volatility and were able to extend AITC shelf life compared with free AITC (65% vs. 20% in 24 h, respectively). Cell viability and uptake of AITC-loaded nanoparticles were studied in vitro, showing that the protection and sustained release of AITC from polymeric NPs involved a larger toxicity of tumoral cells. These nanoparticles could be used as protective systems for enhancing a biological activity.

Fabrication and in-vitro Evaluation of Ketotifen Fumarate-loaded PLGA Nanoparticles as a Sustained Delivery System.

Ketotifen fumarate is a non-bronchodilator anti-asthmatic drug which inhibits the effects of certain endogenous substances known to be inflammatory mediators, and thereby exerts antiallergic activity. The present study describes the formulation of a sustained release nanoparticle (NP) drug delivery system containing ketoftifen, using poly (D,L lactide-co-glycolide) acid (PLGA). Biodegradable NPs were prepared using 50 : 50 PLGA by a water in-oil-in-water (w/o/w) double emulsion-solvent evaporation procedure and characterized for drug content, DSC (differential scanning calorimetry, XRD (X-ray diffractionl), FTIR (Fourier transform spectroscopy), particle size , surface morphology using scanning electron microscopy, and drug release rate. The effects of different drug-to-polymer ratios on the characteristics of the NPs were investigated. NPs prepared were spherical with a smooth surface. Size of NPs was dependent on the concentration of polymer (10 mg/mL, 754.6 nm). Increasing the external organic phase volume (primary emulsion) resulted in larger particles with higher encapsulation efficiency (55%). The best drug to polymer ratio in the NP was F3 (1:10 ratio) which showed loading efficiency of 55%, and mean particle size of 754.6 nm, respectively. The FTIR, XRPD, and DSC results ruled out any chemical interaction between the drug and PLGA. The NPs prepared with low ratio of drug to polymer (1:5) F1 formulation showed faster dissolution rate than those with high drug to polymer ratio (1:10) F3 formulation. In conclusion, by selecting an appropriate level of the investigated parameters, spherical NPs with encapsulation efficiencies higher than 55% and a prolonged drug release over 24h (73.67-90.05%) were obtained.

Preparation and evaluation of a thermosensitive liposomal hydrogel for sustained delivery of danofloxacin using mesoporous silica nanoparticles

Background: Sustained release delivery system can reduce the dosage frequency and maintain the therapeutic level of drugs for a longer time. Biodegradable, biocompatible and thermosensitive chitosan-beta-glycerophosphate (C-GP) solutions can solidify at body temperature and maintain their physical integrity for a longer duration. OBJECTIVES: To develop a novel delivery system based on the integration of liposomes in hydrogel using mesoporous silica nanoparticles (MSNs) for sustained release of danofloxacin in farm animals. METHODS: The MSNs were prepared using N-cetyltrimethylammonium bromide and tetraethylortho silica. The liposomes were prepared by thin film hydration method. C-GP solution containing danofloxacin-loaded MSN liposomes underwent different in-vitro tests, including evaluation of the entrapment efficiency, gelation time, morphology, drug release pattern as well as antimicrobial activities against S. aureus and E. coli. RESULTS: The mean pore size of MSNs was 2.8 nm and the mean MSN entrapment efficiency was 45%. Kinetics of danofloxacin release from liposomal hydrogel followed the Higuchi’s model. This formulation was capable of sustaining the danofloxacin release for more than 96 h. The FTIR studies showed that there were no interactions between danofloxacin and hydrogel excipients. Scanning electron microscopy (SEM) showed that the formed gel had a continuous texture, while the swelled gel in the phosphate buffer had a porous structure. Microbiological tests revealed a high antibacterial activity for lipomosal hydrogel of danofloxacin-loaded MSN comparable with danofloxacin solution. CONCLUSIONS: The liposomal hydrogel solidified at body temperature, effectively sustained the release of danofloxacin and showed in vitro antibacterial effects.

Fabrication of a three-dimensional β-tricalcium-phosphate/gelatin containing chitosan-based nanoparticles for sustained release of bone morphogenetic protein-2: Implication for bone tissue engineering

Fabrication of an ideal scaffold having proper composition, physical structure and able to have sustained release of growth factors still is challenging for bone tissue engineering. Current study aimed to design an appropriate three-dimensional (3-D) scaffold with suitable physical characteristics, including proper compressive strength, degradation rate, porosity, and able to sustained release of bone morphogenetic protein-2 (BMP2), for bone tissue engineering. A highly porous 3-D β-tricalcium phosphate (β-TCP) scaffolds, inside of which two perpendicular canals were created, was fabricated using foam-casting technique. Then, scaffolds were coated with gelatin layer. Next, BMP2-loaded chitosan (CS) nanoparticles were dispersed into collagen hydrogel and filled into the scaffold canals. Physical characteristics of fabricated constructs were evaluated. Moreover, the capability of given construct for bone regeneration has been evaluated in vitro in interaction with human buccal fat pad-derived stem cells (hBFPSCs). The results showed that gelatin-coated TCP scaffold with rhBMP2 delivery system not only could act as a mechanically and biologically compatible framework, but also act as an osteoinductive graft by sustained delivering of rhBMP2 in a therapeutic window for differentiation of hBFPSCs towards the osteoblast lineage. The proposed scaffold model can be suggested for delivering of cells and other growth factors such as vascular endothelial growth factor (VEGF), alone or in combination, for future investigations.

Dimethyl-β-cyclodextrin/salazosulfapyridine inclusion complex-loaded chitosan nanoparticles for sustained release

This study aimed to investigate a novel delivery system for salazosulfapyridine (SASP) through encapsulation in 2,6-dimethyl-β-cyclodextrin (DMβCD) and further incorporation in chitosan (CS) to form nanoparticles (NPs). The inclusion complex of SASP and DMβCD was prepared at 1:1 host–guest stoichiometry based on Job’s plot and then characterized through various analytical techniques. Then, the DMβCD/SASP inclusion complex was incorporated in CS to form DMβCD/SASP/CS NPs. The loading efficiency of SASP in the DMβCD/SASP/CS NPs was significantly higher than that of the SASP/CS NPs. A positive zeta potential of +35.4mV was also observed in the DMβCD/SASP/CS NPs with an average size of 90nm. SASP exhibited a sustained release after the DMβCD/SASP/CS NPs were formed. The toxicity of the NPs to LO2 cells was lower than that of free SASP. Therefore, the CD inclusion complex-loaded CS NPs can be applied to deliver hydrophobic drugs.

Preparation and Characterization of Nateglinide Loaded Hydrophobic Biocompatible Polymer Nanoparticles

The aim of the present study was to develop sustained release Nateglinide loaded Ethylcellulose nanoparticles and characterize the properties of recovered nanoparticles. The sustained release nanoparticles were prepared by oil in water single emulsion solvent evaporation method. The developed nanoparticles were characterised for their particle size, morphology, encapsulation efficiency, drug polymer compatibility and in vitro drug release. The drug polymer compatibility was investigated by XRPD. Imaging of particles was performed by field emission scanning electron microscopy. The highest particle size and encapsulation efficiency of recovered nanoparticles were 248.37 nm and 91.16 % respectively. The recovered nanoparticles are spherical in nature and uniform in size. Developed nanoparticles have low crystallinity than the pure Nateglinide. The highest drug-polymer ratio formulation showed drug release 61.1 ± 1.76 % up to 24 h.

Development of Polymeric Nanoparticles for Sustained Release of Thiabendazole in Agricultural Applications

Thiabendazole entrapped chitosan xanthan gum nanoparticles were synthesized and evaluated for the Aspargillus parasiticus. Synthesis of nanoparticles was done by ionotropic gelation method and optimization was done by central composite design. Concentration of polymers affected the particle size and zeta potential of the particles. In vitro release studies of the thiabendazole were done. Further the nanoformulation shows better results as compared to the pure thiabendazole.

PLGA-based nanoparticles for sustained release of Ca++ for apexification

PLGA-based nanoparticles for sustained release of Ca++ for apexification

Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications.

Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

PLGA nanoparticle formulation of RK-33: an RNA helicase inhibitor against DDX3.

The DDX3 helicase inhibitor RK-33 is a newly developed anticancer agent that showed promising results in preclinical research (Bol et al. EMBO Mol Med, 7(5):648-649, 2015). However, due to the physicochemical and pharmacological characteristics of RK-33, we initiated development of alternative formulations of RK-33 by preparing sustained release nanoparticles that can be administered intravenously. In this study, RK-33 was encapsulated in poly(lactic-co-glycolic acid) (PLGA), one of the most well-developed biodegradable polymers, using the emulsion solvent evaporation method. Hydrodynamic diameter of RK-33-PLGA nanoparticles was about 245 nm with a negative charge, and RK-33-PLGA nanoparticles had a payload of 1.4 % RK-33. RK-33 was released from the PLGA nanoparticles over 7 days (90 ± 5.7 % released by day 7) and exhibited cytotoxicity to human breast carcinoma MCF-7 cells in a time-dependent manner. Moreover, RK-33-PLGA nanoparticles were well tolerated, and systemic retention of RK-33 was markedly improved in normal mice. PLGA nanoparticles have a potential as a parenteral formulation of RK-33.

The use of solid lipid nanoparticles for sustained drug release.

Novel solid lipid drug delivery systems such as solid lipid nanoparticles (SLN) have attracted wide and increasing attention in recent years. It has been sought as an interesting alternative drug delivery carrier system for bioactives for a variety of delivery routes. They show major advantages such as sustained release, improved bioavailability, improved drug incorporation and very wide application. This paper presents a discussion on the production protocols of SLN, lyophilization of SLN and delivery of SLN across the blood-brain barrier. Special attention was also paid to entrapment and release of drugs from SLN and strategies to enhance drug entrapment in SLN for sustained release. Analytical methods for the characterization of SLN were also discussed. Various routes of administration of SLN were presented as well as a consideration of the ethical issues and future prospects in the production and use of SLN for sustained release of bioactives.

Natural Bioadhesive Biodegradable Nanoparticle-Based Topical Ophthalmic Formulations for Management of Glaucoma.

We prepared and characterized topical ophthalmic formulations containing brimonidine-loaded bioadhesive cationic chitosan or anionic alginate nanoparticles (NPs) for sustained release of brimonidine as once daily regimen for management of glaucoma. Nanoparticles were prepared using a spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifiers, and NPs stabilizers were used for formulation optimization. Nanoparticles were characterized regarding particle size, zeta potential, morphology, and drug content. Brimonidine-loaded NPs were incorporated into eye drops, a temperature-triggered in situ gelling system, and a preformed gel. They then were characterized regarding their pH, viscosity, uniformity of drug content, in vitro release characteristics, in vitro cytotoxicity, and in vivo intraocular pressure (IOP) lowering effects. Characteristics of optimized brimonidine-loaded chitosan and alginate NPs, respectively, are: particle size, 115.67 ± 3.58 and 157.67 ± 5.53 nm; zeta potential, +35.27 ± 3.39 and -37.8 ± 3.77 mV; encapsulation efficiency, 74.34% ± 2.05% and 70.40% ± 2.77%; drug loading, 11.81% ± 0.67% and 13.14% ± 0.90%; and yield, 87.91% ± 5.92% and 76.53% ± 3.32%. Transmission electron microscope (TEM) analyses revealed that NPs have spherical shapes with a dense core and distinct coat. Formulations possessed uniform drug content. Furthermore, pH and viscosity were compatible with the eye. Formulations showed a sustained release without any burst effect with a Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are biocompatible. Importantly, all formulations possessed a sustained IOP lowering effect compared to the marketed brimonidine tartrate eye drops. These formulations provide a great improvement in topical ocular brimonidine delivery. The application of a single drop is sufficient to provide extended IOP reduction, which should improve patient compliance. We have developed a novel biocompatible topical delivery system for brimonidine, a first line glaucoma medication. Once daily application should have positive effects on patient compliance and, therefore, preservation of vision.

Biomimetic Intrafibrillar Mineralization of Type I Collagen with Intermediate Precursors-loaded Mesoporous Carriers.

Limited continuous replenishment of the mineralization medium is a restriction for in-situ solution-based remineralization of hypomineralized body tissues. Here, we report a process that generated amine-functionalized mesoporous silica nanoparticles for sustained release of biomimetic analog-stabilized amorphous calcium phosphate precursors. Both two-dimensional and three-dimensional collagen models can be intrafibrillarly mineralized with these released fluidic intermediate precursors. This represents an important advance in the translation of biomineralization concepts into regimes for in-situ remineralization of bone and teeth.

Interaction and release kinetics study of hybrid polymer blend nanoparticles for pH independent controlled release of an anti-viral drug

Incompatible interactions of polymers with active chemical entity offer variable challenges in drug delivery kinetics. This study focuses on development of hybrid polymer blend nanoparticles with amphiphilic (Poly Vinyl Pyrrolidone) and hydrophobic (Ethyl cellulose and Eudragit RSPO) polymers to encapsulate maximum drug without significant incompatibility. Optimized nanoparticles developed using Acyclovir model drug exhibited 80% entrapment with size and surface charge of 100 nm and +26 mV, respectively. Spherical morphology and solid state transition of drug from crystalline to amorphous in nanoparticles was confirmed by SEM and XRD analysis. pH independent in-vitro drug release was observed in four different media with initial burst release followed by sustained release for >12 h. Statistically significant difference (P < 0.05) was observed in percentage of drug release from each formulation in different media. H-bonding and hydrophobic interactions between drug and polymer (FTIR, TG-DTA analysis and Makoid–Banakar Kinetics) and diffusion of drug from matrix nanospheres followed by pore transport were the key factors for effective drug release kinetics. Uptake of nanoparticles by corneal epithelial cells was more prominent within 30 min, however viability of cells was not altered significantly. Release kinetics and interactions studies revealed the suitability of polymer blend nanoparticles for better encapsulation and sustained release of the drug.

Polypyrrole nanoparticles for tunable, pH-sensitive and sustained drug release.

We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (∼15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.

One pot synthesis of doxorubicin loaded gold nanoparticles for sustained drug release

Here, we report a facile, versatile and simple one-pot synthesis of doxorubicin (Dox) loaded gold nanoparticles (Dox–GNP conjugate), where Dox can act both as a reducing as well as a capping agent.

Double loaded self-decomposable SiO₂ nanoparticles for sustained drug release.

Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms-the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the "grown-in" drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window-a sustained drug delivery system with a great impact on improving the management of chronic diseases.

Mesoporous molecularly imprinted polymer nanoparticles as a sustained release system of azithromycin

A combination of a molecular imprinting technique and precipitation polymerization was applied to develop novel azithromycin-imprinted poly(methacrylic acid-co-ethylene glycol dimethacrylate) nanoparticles for sustained release of azithromycin (AZM).