Polyherbal drug loaded starch nanoparticles as promising drug delivery system: Antimicrobial,antibiofilm and neuroprotective studies

Starch is a natural, renewable biopolymer widely used in pharmaceutical industry for the controlled release of drugs and hormones. Triphala Churna (TC) a tridoshic rasayana, rich in polyphenols and vitamin C possess balancing and rejuvenating effect on three constitutional elements that govern the human life. To enhance the solubility and efficiency of the ayurvedic drug TC, attempts were made to encapsulate the TC into starch biopolymers. Characterization of Starch Encapsulated Triphala Churna (SETC) by UV–Vis spectrum, showed a sharp absorption peak at 686 nm specific for polyherbal formulation. XRD analysis illustrated that SETC is amorphous in nature. Zeta potential and dynamic light scattering analysis illustrated that the SETC were highly stable at −12 mV with an average size of 282.9 nm. SETC exhibited high drug encapsulation efficiency and fast drug release at physiological pH 7.4. Evaluation of neuroprotective effect illustrated that SETC showed excellent free radical scavenging activity, reducing power and acetylcholinesterase inhibitory activity. SETC also showed potent antibacterial activity (against Salmonella typhi and Shigella dysenteriae) and antibiofilm activity (against ATCC MRSA 33591 and clinical strain N7). Results conclude that TC on encapsulation with starch retained its antimicrobial, antibiofilm and neuroprotective activities illustrating starch as suitable drug delivery system.     

Multifunctional nanoparticles from albumin for stimuli-responsive efficient dual drug delivery

In this project methotrexate (MTX) conjugated albumin based nanoparticles (MTX-BSA) loaded with curcumin (CUR) drug (CUR-MTX-BSA) for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy were designed. Co-delivery is a new strategy which minimize the amount of each drug, reduce of side effects and also to achieve the synergistic effect for cancer therapies. The MTX was conjugated to albumin via covalent bond. Next, this synthesized prodrug loaded with CUR. Afterward, the formulations were evaluated for physical and chemical properties by DLS, TEM, FTIR, UV/Vis, DSC analysis, in vitro cytotoxicity and in vivo biocompatibility studies. Furthermore, the drug loading and release study were evaluated. Proteinase K enzyme was used to break amid bond between MTX and BSA and also amidic bonds in BSA structure. Administration of up to 2000 mg/kg of BSA to healthy animals was non-toxic and all treated mice were still alive after 24 h. The result of this study proved that CUR-MTX-BSA can be used as a proficient vehicle for effective co-delivery of CUR and MTX in the treatment of cancer.     

Formation of core/shell nanoparticles with a lipid core and their application as a drug delivery system

A novel preparation method for core/shell nanoparticles with a drug-loaded lipid core was designed and characterized. The lipid core is composed of lecithin and a drug, and the polymeric shell is composed of Pluronics (poly(ethylene oxide)-poly (propylene oxide)-poly(ethylene oxide) triblock copolymer, F-127). For the formation of stabilized core/shell nanoparticles, freeze-drying was performed in the presence of trehalose used as a cryoprotectant. Cryogenic transmittance electron microscopy (cryo-TEM), differential scanning calorimetry (DSC), and a particle size analyzer were used to observe the formation of the stabilized core/shell nanoparticles. For the application of the core/shell nanoparticles as a drug carrier, paclitaxel, a potent anticancer drug, was loaded into the core/shell nanoparticles, and the drug loading amount and the drug release pattern were observed.     

Gold nanoparticles: Emerging paradigm for targeted drug delivery system

The application of nanotechnology in medicine, known as nanomedicine, has introduced a plethora of nanoparticles of variable chemistry and design considerations for cancer diagnosis and treatment. One of the most important field is the design and development of pharmaceutical drugs, based on targeted drug delivery system (TDDS). Being inspired by physio-chemical properties of nanoparticles, TDDS are designed to safely reach their targets and specifically release their cargo at the site of disease for enhanced therapeutic effects, thereby increasing the drug tissue bioavailability. Nanoparticles have the advantage of targeting cancer by simply being accumulated and entrapped in cancer cells. However, even after rapid growth of nanotechnology in nanomedicine, designing an effective targeted drug delivery system is still a challenging task. In this review, we reveal the recent advances in drug delivery approach with a particular focus on gold nanoparticles. We seek to expound on how these nanomaterials communicate in the complex environment to reach the target site, and how to design the effective TDDS for complex environments and simultaneously monitor the toxicity on the basis of designing such delivery complexes. Hence, this review will shed light on the research, opportunities and challenges for engineering nanomaterials with cancer biology and medicine to develop effective TDDS for treatment of cancer.     

Fibrin nanoparticles as Possible vehicles for drug delivery

Background

Several issues have been raised emphasizing the harmful toxic effects of metal nanoparticles towards biological systems. Search of biological nanoparticles with excellent biocompatibility and bioavailability could address this problem.

Methods

Fibrin nanoparticles (FNP) were prepared using a novel technique and characterized for their physico-chemical properties. In vitro studies were performed to examine cytotoxicity and cellular uptake of FNP. Innate immune response to FNP was studied by (i) estimating in vitro generation of complement split products, C3a and C4d and (ii) in vivo expression of pro-inflammatory cytokines, TNF-α, IL-1 and IL-6. In vivo biodistribution study was carried out by intravenous administration of FITC-labelled FNP in mice.

Results

FNP were spherical with size ranging from 25 to 28 nm. In vitro studies proved the biocompatibility of the nanoparticles, with their distribution across the cytoplasm and nucleus of treated cells. Complement activation studies showed insignificant increase in the level of C3a when compared with positive control. RT-PCR results revealed significant upregulation of TNF-α and downregulation of IL-6 cytokines after 6 h of FNP administration. In vivo biodistribution studies showed moderate blood circulation time, with predominant distribution of nanoparticles in the liver followed by the lungs, kidney and spleen. Haematology, serum biochemistry, and histopathology analyses demonstrated that FNP were non-toxic.

Conclusion

Owing to their small size, low cost, ease of preparation and excellent biocompatibility, FNP might be a promising novel material for drug delivery applications.

General significance

Our results demonstrate the safe and promising use of FNP for biomedical applications.     

脂质体药物传递系统

脂质体已经发展成为一种成熟的传递系统,从脂质体作为载体概念的提出发展到生产制药水平历经了很长的发展阶段,如今脂质体制剂已有效地应用于重要疾病的治疗领域。简述了有关药物传递脂质体的目标和系统,透视了那些正在研究的领域,以及有哪些机会可合理改进脂质体的药物治疗。     

Microparticles and nanoparticles for drug delivery

Particulate drug delivery systems have become important in experimental pharmaceutics and clinical medicine. The distinction is often made between micro- and nanoparticles, being particles with dimensions best described in micrometers and nanometers respectively. That size difference entails real differences at many levels, from formulation to in vivo usage. Here I will discuss those differences and provide examples of applications, for local and systemic drug delivery. I will outline a number of challenges of interest in particulate drug delivery.     

Toxicity of gold nanoparticles for plants in experimental aquatic system

Increased production and use of nanomaterials can lead to new types of pollution of the environment, including aquatic ecosystems. Pollution of the aqueous environment with nanoparticles can be a new type of pollution of the environment. This requires a more detailed study of the biological effects during exposure of nanoparticles on aquatic organisms. The interactions of gold nanoparticles (Au) with aquatic macrophytes Ceratophyllum demersum have been studied. Aquatic microcosms with these plants were used. Gold nanoparticles (Au) were added to the aqueous medium of C. demersum macrophyte containing microcosms. The state of the plants was then analyzed. Phytotoxicity of Au nanoparticles for aquatic macrophytes was shown for the first time. A new method of phytotoxicity detection was suggested and successfully approved. Phytotoxicity at a concentration of Au (in the form of nanoparticles) of 6 × 10^?6 M-1.8 × 10^?5 M was shown.     

Spectroscopic studies of interaction between CuO nanoparticles and bovine serum albumin

Recently, the great interests in manufacturing and application of metal oxide nanoparticles in commercial and industrial products have led to focus on the potential impact of these particles on biomacromolecules. In the present study, the interaction of copper oxide (CuO) nanoparticles with bovine serum albumin (BSA) was studied by spectroscopic techniques. The zeta potential value for BSA and CuO nanoparticles with average diameter of around 50 nm at concentration of 10 μM in the deionized (DI) water were ?5.8 and ?22.5 mV, respectively. Circular dichroism studies did not show any changes in the content of secondary structure of the protein after CuO nanoparticles interaction. Fluorescence data revealed that the fluorescence quenching of BSA by CuO nanoparticles was the result of the formed complex of CuO nanoparticles – BSA. Binding constants and other thermodynamic parameters were determined at three different temperatures. The hydrogen bond interactions are the predominant intermolecular forces to stabilize the CuO nanoparticle – BSA complex. This study provides important insight into the interaction of CuO nanoparticles with proteins, which may be of importance for further application of these nanoparticles in biomedical applications.     

Combined experimental/computational aspects for the molecular interaction of empagliflozin with bovine serum albumin: Quantification and application to human plasma

Empagliflozin (EMP) is an oral antihyperglycemic agent for type 2 diabetic patients. The molecular binding of EMP to bovine serum albumin (BSA) was elucidated by a combined experimental/computational approach to fulfil the pharmacokinetics and pharmacodynamics gaps of the cited drug for further development. Fluorescence, synchronous, and three-dimensional fluorescence spectroscopy verified that EMP quenched BSA native fluorescence through a dual static/dynamic mechanism that was further supported by Fӧrster resonance energy transfer and ultraviolet absorption spectroscopy. Fourier transform infrared spectroscopy revealed the conformational variations in BSA secondary structure induced by EMP. Thermodynamic properties of the BSA–EMP complex were also investigated, and the hydrophobic interactions' role in the binding process was demonstrated by the computed enthalpy (ΔH = 6.558 kJ mol⁻¹) and entropy (ΔS = 69.333 J mol⁻¹ K⁻¹). Gibbs free energy (ΔG) values were negative at three distinct temperatures, illuminating the spontaneity of this interaction. In addition, molecular docking studies depicted the optimal fitting of EMP to BSA on Site I (sub-domain IIA) through three hydrogen bonds. Additionally, and based on the quenching effect of EMP on BSA fluorescence, this study suggests a simple validated spectrofluorometric method for the quantitation of the studied drug in bulk form and human plasma samples with reasonable recoveries (96.99–103.10%).     

Magnetic nanoparticles for gene and drug delivery

Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting.     

Experimental and computational studies on the binding of diazinon to human serum albumin

In the present research, the binding properties of diazinon (DZN), as an organophosphorus herbicide, to human serum albumin (HSA) were investigated using combination of spectroscopic, electrochemistry, and molecular modeling techniques. Changes in the UV–Vis and FT-IR spectra were observed upon ligand binding along with a significant degree of tryptophan fluorescence quenching on complex formation. The obtained results from spectroscopic and electrochemistry experiments along with the computational studies suggest that DZN binds to residues located in subdomains IIA of HSA with binding constant about 1410.9 M^?1 at 300 K. From the thermodynamic parameters calculated according to the van’t Hoff equation, the enthalpy change ΔH° and entropy change ΔS° were found to be ?16.695 and 0.116 KJ/mol K, respectively. The primary binding pattern is determined by hydrophobic interaction and hydrogen binding occurring in so-called site I of HSA. DZN could slightly alter the secondary structure of HSA. All of experimental results are supported by computational techniques such as docking and molecular dynamics simulation using a HSA crystal model.     

Magnetic nanoparticles for multi-imaging and drug delivery

Various bio-medical applications of magnetic nanoparticles have been explored during the past few decades. As tools that hold great potential for advancing biological sciences, magnetic nanoparticles have been used as platform materials for enhanced magnetic resonance imaging (MRI) agents, biological separation and magnetic drug delivery systems, and magnetic hyperthermia treatment. Furthermore, approaches that integrate various imaging and bioactive moieties have been used in the design of multi-modality systems, which possess synergistically enhanced properties such as better imaging resolution and sensitivity, molecular recognition capabilities, stimulus responsive drug delivery with on-demand control, and spatio-temporally controlled cell signal activation. Below, recent studies that focus on the design and synthesis of multi-mode magnetic nanoparticles will be briefly reviewed and their potential applications in the imaging and therapy areas will be also discussed.     

Core/shell nanofibers with embedded liposomes as a drug delivery system

The broader application of liposomes in regenerative medicine is hampered by their short half-life and inefficient retention at the site of application. These disadvantages could be significantly reduced by their combination with nanofibers. We produced 2 different nanofiber-liposome systems in the present study, that is, liposomes blended within nanofibers and core/shell nanofibers with embedded liposomes. Herein, we demonstrate that blend electrospinning does not conserve intact liposomes. In contrast, coaxial electrospinning enables the incorporation of liposomes into nanofibers. We report polyvinyl alcohol-core/poly-ε-caprolactone-shell nanofibers with embedded liposomes and show that they preserve the enzymatic activity of encapsulated horseradish peroxidase. The potential of this system was also demonstrated by the enhancement of mesenchymal stem cell proliferation. In conclusion, intact liposomes incorporated into nanofibers by coaxial electrospinning are very promising as a drug delivery system.     

Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery

Nanoparticles of approximately 10nm in diameter made with chitosan or lactic acid-grafted chitosan were developed for high drug loading and prolonged drug release. A drug encapsulation efficiency of 92% and a release rate of 28% from chitosan nanoparticles over a 4-week period were demonstrated with bovine serum protein. To further increase drug encapsulation, prolong drug release, and increase chitosan solubility in solution of neutral pH, chitosan was modified with lactic acid by grafting D,L-lactic acid onto amino groups in chitosan without using a catalyst. The lactic acid-grafted chitosan nanoparticles demonstrated a drug encapsulation efficiency of 96% and a protein release rate of 15% over 4 weeks. With increased protein concentration, the drug encapsulation efficiency decreased and drug release rate increased. Unlike chitosan, which is generally soluble only in acid solution, the chitosan modified with lactic acid can be prepared from solutions of neutral pH, offering an additional advantage of allowing proteins or drugs to be uniformly incorporated in the matrix structure with minimal or no denaturization.     

红细胞伪装纳米颗粒:一个具有潜力的药物及疫苗递送系统

红细胞伪装纳米颗粒是一种以红细胞或红细胞膜纳米囊泡为载体在体内递送药物、酶、多肽和抗原等物质的系统,具有生物相容性好、循环周期长、靶向性强等优势。本文从红细胞载体的种类、发展历程、递送策略应用以及其局限性和未来的挑战等方面进行了详细阐述,并展望了其未来的发展方向。     

Synthesis of 6-O-methotrexylhyaluronan as a drug delivery system

Selective halogenation of hyaluronan and partial halogen substitution by methotrexate led to 6-chloro-6-deoxy-6-O-methotrexylhyaluronan, a potential antitumor drug. The remaining halogen could be further substituted by a second organic carboxylate, leading to mixed esters. 6-O-Acetyl-6-O-methotrexylhyaluronan and 6-O-butyryl-6-O-methotrexylhyaluronan were thus synthesized and characterized by NMR spectroscopy.     

Tuftsin-modified alginate nanoparticles as a noncondensing macrophage-targeted DNA delivery system

The main objective of this study was to evaluate macrophage-targeted alginate nanoparticles as a noncondensing gene delivery system for potential anti-inflammatory therapy. An external gelation method was employed to form plasmid DNA-encapsulated alginate nanoparticles. The nanoparticle surface was modified with a peptide sequence containing tuftsin (TKPR), and transfection efficiency was determined in J774A.1 macrophages. The effect of transfected mIL-10 in blocking expression of tumor necrosis factor-alpha (TNF-α) was evaluated in lipopolysaccharide (LPS)-stimulated cells. Scrambled peptide- and tuftsin-modified cross-linked alginate nanoparticles efficiently encapsulated plasmid DNA and protected against DNase I degradation. The transgene expression efficiencies, measured using GFP and mIL-10 expressing plasmid DNA, were highest with tuftsin-modified nanoparticles. Levels of TNF-α were significantly lower (p < 0.0001) in LPS-stimulated cells that were transfected with mIL-10 using alginate nanoparticles. The results of the study show that noncondensing alginate nanoparticles can efficiently deliver plasmid DNA, leading to sustained in vitro gene expression in macrophages.     

Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: A review

The purpose of this review is to give an insight into the considerable potential of lecithin organogels (LOs) in the applications meant for topical drug delivery. LOs are clear, thermodynamically stable, viscoelastic, and biocompatible jelly-like phases, chiefly composed of hydrated phospholipids and appropriate organic liquid. These systems are currently of interest to the pharmaceutical scientist because of their structural and functional benefits. Several therapeutic agents have been formulated as LOs for their facilitated transport through topical route (for dermal or transdermal effect), with some very encouraging results. The improved topical drug delivery has mainly been attributed to the biphasic drug solubility, the desired drug partitioning, and the modification of skin barrier function by the organogel components. Being thermodynamically stable, LOs are prepared by spontaneous emulsification and therefore posses prolonged shelf life. The utility of this novel matrix as a topical vehicle has further increased owing to its very low skin irritancy potential. Varied aspects of LOs viz formation, composition, phase behavior, and characterization have been elaborated, including a general discussion on the developmental background. Besides a comprehensive update on the topical applications of lecithin organogels, the review also includes a detailed account on the mechanistics of organogelling. Published: October 6, 2005