Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery

In ocular drug delivery, a major problem is providing an adequate concentration of a therapeutic agent in the precorneal area. Mucoadhesive carriers such as polyacrylic acid in sub-colloidal, nanoparticulate form, have a strong potential for ophthalmic drug delivery. A formulation of brimonidine loaded in polyacrylic acid nanoparticles has been prepared for potential delivery in ophthalmic therapy. The particles were prepared by a reverse microemulsion polymerization technique and their sizes were in the range of 50 nm. In a preliminary biocompatibility test, Caco-2 cells (human primary colonic tumour adenocarcinoma) and human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability over varying times. The loading efficiency of the drug brimonidine in the particles was shown to be between 80–85% and pH dependent. The bioadhesive polyacrylic hydrogel nanoparticles, used in the present study, exhibited superior loading properties for brimonidine, and the formulation was stable for more than 5 weeks. When the drug-loaded nanoparticles were dispersed in a phosphate buffer saline (pH = 7.4), the drug was slowly released over several hours. Two-photon laser scanning microscopic studies of dye-conjugated polyacrylic acid nanoparticles demonstrated the accumulation of the particles on the surface and intercellular spaces of Caco-2 cells.     

In-vitro cytotoxicity and cell uptake study of gelatin-coated magnetic iron oxide nanoparticles

The aim of this study was to modify the surfaces of magnetic iron oxide nanoparticles (IOPs) with gelatin in order to reduce cytotoxicity and enhance cellular uptake. The gelatin-coated IOPs were characterized in terms of their functionalization, size, surface charge, morphology and crystalline structure using Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), dynamic light scattering (DLS), transmission electron microscopy (BIO-TEM) and x-ray diffraction (XRD) analysis. The cytotoxicity of the gelatin-coated IOPs to human fibroblasts was assessed using an MTT-assay and was compared with uncoated IOPs. Similarly, the cellular uptake of the coated and uncoated IOPs was visualized using BIO-TEM and quantified using inductively coupled plasma spectroscopy (ICPS). As shown by the Fourier emission scanning electron microscopy (FE-SEM) and viability test, the massive uptake of uncoated IOPs lead to reduced viability. However, gelatin coating lead to increased viability and slow uptake without any visible distortion to the cell morphology.     

Genipin crosslinked curcumin loaded chitosan/montmorillonite K-10 (MMT) nanoparticles for controlled drug delivery applications

Abstract

Here, we have reported the influence of MMT and genipin in releasing curcumin from the Genipin crosslinked Chitosan/MMT nanoparticles, prepared by ionic gelation method. The nanoparticles were characterised using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). Zeta potential and average diameter of the nanoparticles were found in the range 32–47?mV and 430–560?nm. Swelling and release of curcumin from the nanoparticles increased with the decrease in pH of the medium, MMT, and genipin content. Curcumin released from the nanoparticles reduced the viability of MCF-7 and Hep G2 cells as compared to untreated cells. The nanoparticles increased the level of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase level in human PBMCs and decreased the level of Lipid peroxidation suggesting an enhanced protection against cellular damage. Lower pH and higher MMT concentration in the nanoparticles improved the mucoadhesive properties.     

Encapsulation of hydrophobic aroma in whey protein nanoparticles

Aroma-loaded nanoparticles (d?<?300?nm) were prepared by cross-linking denatured whey protein through pH-cycling. The effect of nanoparticulation conditions and aroma concentration on the physicochemical characteristics of nanoparticles and aroma release profile was studied. Better retention of aroma was observed when ethyl hexanoate was added before nanoparticle formation. The highest aroma retention was obtained for nanoparticles produced at pH 5.0 and 5.5 without calcium addition. These nanoparticles are characterized by a less compact and more porous internal structure allowing a higher loading of aroma. Increasing aroma concentration increased the diameter and the voluminosity of the aroma-loaded nanoparticles. The percentage of aroma retention showed an increase from 7% to 24% over the tested concentration range while the value averaged 2% for native or denatured whey protein. Encapsulation of ethyl hexanoate in whey protein nanoparticles reduced the mass transfer of aroma at the surface of the matrix and improved its retention.     

Effects of pH-sensitive nanoparticles prepared with different polymers on the distribution,adhesion and transition of Rhodamine 6G in the gut of rats

To investigate the effect of different enteric polymers on the characteristics of pH-sensitive nanoparticles, Rhodamine 6G (Rho) was incorporated in various pH-sensitive nanoparticles. The different patterns of pH-dependent release profiles were observed, although some polymers have the same dissolving pH. The distribution, adhesion and transition of different nanoparticles in rat gut showed significant difference, closely related to the release characteristics of nanoparticles, and their release behaviour are dependent on the dissolving pH and the structure of the polymers, as well as the drug property. Most nanoparticle formulations decreased the distribution and adhesion of Rho in the stomach but increased these values in the intestine. The nanocarriers also control the drug release sites and release rate in the GI tract. In conclusion, pH-sensitive nanoparticles seem favourable for drug absorption and it is important to choose the proper materials to obtain the suitable characteristics for the oral pH-sensitive nanoparticles.     

Bioadhesive properties of poly(anhydride) nanoparticles coated with different molecular weights chitosan

The aim of this study was to develop and characterize the bioadhesive properties of poly(anhydride) nanoparticles coated with two types of low-molecular weight chitosan (CH20 of 20?kDa or CH50 of 50?kDa) or their thiolated conjugates. Nanoparticles were prepared by a solvent displacement method and characterized by measuring the size, zeta potential, morphology and composition. For bioadhesion studies, nanoparticles were fluorescently labelled with rhodamine B isothiocyanate. In all cases, coated nanoparticles showed a slightly higher size and lower negative zeta potential than uncoated nanoparticles. Nanoparticles coated with CH20 showed a higher adhesive capacity than uncoated nanoparticles. On the contrary, when nanoparticles were coated with CH50, the resulting carriers displayed a decreased ability to develop adhesive interactions within the gut. Finally, the coating of nanoparticles with thiolated chitosan improved their adhesive abilities. Poly(anhydride) nanoparticles coated with thiolated chitosan can be considered as promising bioadhesive particulate carriers for oral delivery strategies.     

Glutathione decorated gold-magnetic nanoparticles: efficient and recyclable catalyst for biotechnological and pharmaceutical applications

Abstract

Nowadays, since the core-shell gold-magnetite nanoparticles include the saturation magnetisation (iron oxide) and plasmon surface (gold shell) properties, they have been considered in biological and biomedicine research areas. In the present work, multifunctional glutathione decorated gold-coated iron oxide nanoparticles (GSH-AuMNPs) were successfully synthesised and fully characterised. From the absorption peak at 525, the formation of the core-shell GSH-AuMNPs was confirmed. Although the saturation magnetisation value was slightly decreased during the formation process, they were easily recovered through magnetic decantation. The biocompatibility of the synthesised NPs was approved by the cytotoxicity researches. Furthermore, the GSH-AuMNPs indicated a good catalytic activity for the catalytic reduction of 2-nitrophenol by sodium borohydride and reused for six consecutive cycles without a significant decrease in its activity. Overall, this study introduced a unique structure with high catalytic activity, which could provide a useful platform for the biomedical, analytical, catalytic applications and wastewater treatment.     

Tamoxifen-loaded nanoparticles based on a novel mixture of biodegradable polyesters: characterization and in vitro evaluation as sustained release systems

Nanoparticles (NP) from mixtures of two poly(D,L-lactide-co-caprolactone) (PLC) copolymers, PLC 40/60 and PLC 86/14, with poly(D,L-lactide) (PDLLA) and PCL were prepared: PLC 40/60-PCL (25:75), PLC 86/14-PCL (75:25) and PLC 86/14-PLA (75:25). Tamoxifen was loaded with encapsulation efficiency between 65% and 75% (29.9–36.3?µg TMX/ mg NP). All selected systems showed spherical shape and nano-scale size. TMX-loaded NPs were in the range of 293–352?nm. TMX release from NP took place with different profiles depending on polymeric composition of the particles. After 60 days, 59.81% and 82.65% of the loaded drug was released. The cytotoxicity of unloaded NP in MCF7 and HeLa cells was very low. Cell uptake of NP took place in both cell types by unspecific internalization in a time dependent process. The administration of 6 and 10?µm TMX by TMX-loaded NP was effective on both cellular types, mainly in MCF7 cells.     

Ciprofloxacin hydrochloride-loaded glyceryl monostearate nanoparticle: factorial design of Lutrol F68 and Phospholipon 90G

Purpose: This investigation was undertaken to develop glyceryl monostearate (Geleol)-based solid lipid nanoparticles (SLNs) of a hydrophilic drug ciprofloxacin HCl.

Methods: Hansen's solubility parameter study was carried out in screening of a suitable carrier and solvent system. Subsequently, SLNs were prepared by solvent diffusion evaporation method and investigated for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE) and drug release behaviour.

Results: Variations in SLN composition resulted in particle sizes between 170 and 810?nm and ZPs between 8 and 14?mV. The maximum EE was found to be 26.3% with particle size of 188.8?nm. SLN can sustain the release of drug for up to 15?h and it shows Higuchi matrix model as the best-fitted model. SLNs were stable without aggregation of particles under storage conditions.

Conclusions: The results of this study provide the framework for further study involving the SLN formulation for hydrophilic drug molecule.     

Lymphatic uptake of lipid nanoparticles following endotracheal administration

A previous publication reported the uptake into the lymphatics of pulmonary administered lipid nanoparticles (LN), after aerosolization and inhalation. In the present study LN clearance from the lungs and lymphatic uptake were further evaluated after endotracheal administration. Nanoparticles prepared with gliceryl behenate were radiolabelled by association to the lipophilic tracer D,L-hexamethylpropylene amine oxime (HMPAO) coupled with ^99mTc. Labelling efficiency was 97% and stability in body fluids was demonstrated in vitro. Wistar rats were treated by endotracheal administration and lymphatic uptake was determined upon organ sampling. Endotracheally delivered LN are rapidly eliminated from rat lungs and accumulation in para-aortic, axillary and inguinal lymph nodes starts almost immediately after administration. Translocation of LN across the lung mucosa and their uptake into the lymphatics demonstrate their usefulness as potential drug carriers for lung cancer therapy, as well as for immunization purposes.