Shape dependence of gold nanoparticles on in vivo acute toxicological effects and biodistribution

The toxicity and biodistribution in vivo of various morphologies of Au nanoparticles (AuNPs) were studied by using KM mice. The quantitative analysis of Au in each tissue of mice was done by using the Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Sphere-shaped AuNPs displayed the best biocompatibility, compared with rod- and cube-shaped of AuNPs, and rod-shaped AuNPs was more toxic than cube-shaped AuNPs. In vivo biodistribution study revealed all AuNPs were preferentially accumulated in organ of liver and spleen. The findings from this study thus revealed that the toxicity and biodistribution in vivo of AuNPs are shape dependent.     

Biocompatibility, efficacy and biodistribution of Gelucire-stabilized nanoparticles engineered for docetaxel delivery

Docetaxel is a potent anticancer agent that will benefit greatly from alternative delivery systems that can overcome several reported adverse effects due to the drug itself and/or the solvent system in the current clinical formulation. In this regard, a new nanoparticle delivery system for docetaxel was prepared from Gelucire-based nanoemulsions by using binary mixtures of Gelucire 44/14 and cetyl alcohol as NP matrix materials. Various amounts of docetaxel (50-1000 microg/ml) were added to the oil phase of the nanoemulsions prior to obtaining solid nanoparticles. The nanoparticles (100-140 nm) achieved high entrapment efficiency (> or = 89%) of docetaxel which was maintained upon storage at 4 degrees C and 25 degrees C. Additional data indicated the Gelucire component in NP played influential roles in drug release possibly by facilitating diffusion from NPs and/or accelerating erosion of NP matrix. Docetaxel-loaded nanoparticles did not cause any significant red blood cell lysis or platelet aggregation nor activate macrophages. Also in-vitro antitumor efficacy in human lung adenocarcinoma cells was demonstrated based on cell cytotoxicity, production of reactive oxygen species and reduction of mitochondrial potential. Enhancement of in-vitro antitumor effects of docetaxel with Gelucire-based NPs could be ascribed to improved particle dispersion and efficient cell permeability. Studies in BALB/c mice demonstrated the stability/retention of NPs in blood circulation and the potential in facilitating docetaxel absorption across the peritoneal cavity. The nanoparticles reported herein may be effective as novel biocompatible and effective delivery systems for docetaxel.     

Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy

The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) copolymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibits an IC(50) = 0.77 ± 0.11 μM comparable to that of free cisplatin (IC(50) = 0.44 ± 0.09 μM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and release cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibit significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo, with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.     

Rationally designed oxaliplatin-nanoparticle for enhanced antitumor efficacy

Nanoscale drug delivery vehicles have been extensively studied as carriers for cancer chemotherapeutics. However, the formulation of platinum chemotherapeutics in nanoparticles has been a challenge arising from their physicochemical properties. There are only a few reports describing oxaliplatin nanoparticles. In this study, we derivatized the monomeric units of a polyisobutylene maleic acid copolymer with glucosamine, which chelates trans-1,2-diaminocyclohexane (DACH) platinum (II) through a novel monocarboxylato and O --> Pt coordination linkage. At a specific polymer to platinum ratio, the complex self-assembled into a nanoparticle, where the polymeric units act as the leaving group, releasing DACH-platinum in a sustained pH-dependent manner. Sizing was done using dynamic light scatter and electron microscopy. The nanoparticles were evaluated for efficacy in vitro and in vivo. Biodistribution was quantified using inductively coupled plasma atomic absorption spectroscopy (ICP-AAS). The PIMA-GA-DACH-platinum nanoparticle was found to be more active than free oxaliplatin in vitro. In vivo, the nanoparticles resulted in greater tumor inhibition than oxaliplatin (equivalent to 5 mg kg?1 platinum dose) with minimal nephrotoxicity or body weight loss. ICP-AAS revealed significant preferential tumor accumulation of platinum with reduced biodistribution to the kidney or liver following PIMA-GA-DACH-platinum nanoparticle administration as compared with free oxaliplatin. These results indicate that the rational engineering of a novel polymeric nanoparticle inspired by the bioactivation of oxaliplatin results in increased antitumor potency with reduced systemic toxicity compared with the parent cytotoxic. Rational design can emerge as an exciting strategy in the synthesis of nanomedicines for cancer chemotherapy.     

Controlling in vivo stability and biodistribution in electrostatically assembled nanoparticles for systemic delivery

This paper demonstrates the generation of systemically deliverable layer-by-layer (LbL) nanoparticles for cancer applications. LbL-based nanoparticles designed to navigate the body and deliver therapeutics in a programmable fashion are promising new and alternative systems for drug delivery, but there have been very few demonstrations of their systemic delivery in vivo due to a lack of knowledge in building LbL nanofilms that mimic traditional nanoparticle design to optimize delivery. The key to the successful application of these nanocarriers in vivo requires a systematic analysis of the influence of film architecture and adsorbed polyelectrolyte outer layer on their pharmacokinetics, which has thus far not been examined for this new approach to nanoparticle delivery. Herein, we have taken the first steps in stabilizing and controlling the systemic distribution of multilayer nanoparticles. Our findings highlight the unique character of LbL systems; the electrostatically assembled nanoparticles gain increased stability in vivo with larger numbers of deposited layers, and the final layer adsorbed generates a critical surface cascade, which dictates the surface chemistry and biological properties of the nanoparticle. This outer polyelectrolyte layer dramatically affects not only the degree of nonspecific particle uptake, but also the nanoparticle biodistribution. For hyaluronic acid (HA) outer layers, a long blood elimination half-life (～9 h) and low accumulation (～10-15% recovered fluorescence/g) in the liver were observed, illustrating that these systems can be designed to be highly appropriate for clinical translation.     

HER‐2 aptamer‐targeted Ecoflex® nanoparticles loaded with docetaxel promote breast cancer cells apoptosis and anti‐metastatic effect

Breast cancer is a major cause of cancer mortality. Regarding the advantages of polymeric nanoparticles as drug delivery systems with targeting potential, in this study the antitumor mechanism of targeted docetaxel polymeric nanoparticles of Ecoflex^® was exploited. Since the overexpression of HER‐2 receptor in breast cancer cases is associated with poor prognosis and more aggressive disease, the proposed nanoparticles were conjugated to HER‐2 specific aptamer molecules. In vitro cytotoxicity was evaluated by MTT assay. Flow‐cytometry analysis was performed to evaluate the cellular uptake of nanoparticles loaded with a fluorescent probe. Anti‐migration effects of samples were studied. Annexin IV‐FITC and propidium iodide were implemented to investigate apoptosis induction and cell cycle analysis. Enhanced cytotoxicity compared with free docetaxel was explained considering improved cellular uptake of the nanoparticles and induced apoptosis in a larger portion of cells. Lower relative migration demonstrated enhanced anti‐migration effect of nanoparticles, and cell cycle was arrested in G2/M phase using both formulations so the anti‐microtubule mechanism of the drug was not altered. Therefore, this system could offer a potential substitute for the currently marketed docetaxel formulations, which may reduce adverse effects of the drug, while further in vivo and clinical investigations are required.Inspec keywords: cancer, molecular biophysics, drug delivery systems, fluorescence, biomedical materials, drugs, tumours, nanomedicine, proteins, toxicology, biochemistry, nanoparticles, diseases, cell motility, polymersOther keywords: antitumor mechanism, targeted docetaxel polymeric nanoparticles, HER‐2 specific aptamer molecules, MTT assay, flow‐cytometry analysis, annexin IV‐FITC, apoptosis induction, cell cycle, lower relative migration, cancer mortality, drug delivery systems, aggressive disease, in vitro cytotoxicity, cellular uptake, breast cancer cell apoptosis, antimetastatic effect, HER‐2 aptamer‐targeted Ecoflex nanoparticles, antimigration effect, antimicrotubule mechanism, HER‐2 receptor, fluorescent probe, propidium iodide     

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

Irinotecan is one of the main chemotherapeutic agents for colorectal cancer (CRC). MicroRNA‐200 (miR‐200) has been reported to inhibit metastasis in cancer cells. Herein, pH‐sensitive and peptide‐modified liposomes and solid lipid nanoparticles (SLN) are designed for encapsulation of irinotecan and miR‐200, respectively. These peptides include one cell‐penetrating peptide, one ligand targeted to tumor neovasculature undergoing angiogenesis, and one mitochondria‐targeting peptide. The peptide‐modified nanoparticles are further coated with a pH‐sensitive PEG‐lipid derivative with an imine bond. These specially‐designed nanoparticles exhibit pH‐responsive release, internalization, and intracellular distribution in acidic pH of colon cancer HCT116 cells. These nanoparticles display low toxicity to blood and noncancerous intestinal cells. Delivery of miR‐200 by SLN further increases the cytotoxicity of irinotecan‐loaded liposomes against CRC cells by triggering apoptosis and suppressing RAS/β‐catenin/ZEB/multiple drug resistance (MDR) pathways. Using CRC‐bearing mice, the in vivo results further indicate that irinotecan and miR‐200 in pH‐responsive targeting nanoparticles exhibit positive therapeutic outcomes by inhibiting colorectal tumor growth and reducing systemic toxicity. Overall, successful delivery of miR and chemotherapy by multifunctional nanoparticles may modulate β‐catenin/MDR/apoptosis/metastasis signaling pathways and induce programmed cancer cell death. Thus, these pH‐responsive targeting nanoparticles may provide a potential regimen for effective treatment of colorectal cancer.     

Gold nanoparticles: a revival in precious metal administration to patients

Gold has been used as a therapeutic agent to treat a wide variety of rheumatic diseases including psoriatic arthritis, juvenile arthritis, and discoid lupus erythematosus. Although the use of gold has been largely superseded by newer drugs, gold nanoparticles are being used effectively in laboratory based clinical diagnostic methods while concurrently showing great promise in vivo either as a diagnostic imaging agent or a therapeutic agent. For these reasons, gold nanoparticles are therefore well placed to enter mainstream clinical practice in the near future. Hence, the present review summarizes the chemistry, pharmacokinetics, biodistribution, metabolism, and toxicity of bulk gold in humans based on decades of clinical observation and experiments in which gold was used to treat patients with rheumatoid arthritis. The beneficial attributes of gold nanoparticles, such as their ease of synthesis, functionalization, and shape control are also highlighted demonstrating why gold nanoparticles are an attractive target for further development and optimization. The importance of controlling the size and shape of gold nanoparticles to minimize any potential toxic side effects is also discussed.     

Solid lipid nanoparticles with and without hydroxypropyl-β-cyclodextrin: a comparative study of nanoparticles designed for colonic drug delivery

New solid lipid nanoparticles (SLN), composed of Compritol ATO888 (C) and hydroxypropyl-β-cyclodextrin (HP), were developed in order to study a new colon-specific formulation for diclofenac sodium (D) delivery. The prepared batches differ from each other by the molecular ratio between HP and D and by the composition of the matrix. Nanoparticles composed of an exclusively lipid matrix and nanoparticles with an oligomeric and lipid matrix were compared in order to establish the effect of both components on the drug delivery tests performed. The SLN preparation method was based on the oil/water hot homogenization process. Emulsions produced were cooled at room temperature and lyophilized in order to obtain dried nanoparticles; possible damage to nanoparticle shape and size was avoided by the addition of cryoprotectants to the aqueous dispersion of nanoparticles before exsiccation. An in vitro toxicity study was performed using CaCo(2) cells to establish the safety of the prepared SLN. Data obtained showed that production method studied guarantees emulsions composed of nanosized drops which can be dried by lyophilization into SLN with a size range of 300-600 nm. In vitro and ex vivo tests demonstrated that dried SLN can be considered as colon delivery systems; however, the matrix composition as well as the presence of cryoprotectant on their surface influences the release and permeation rate of D. The in vitro toxicity studies indicated that the SLN are well tolerated.     

Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting

Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, with multifunctional features that circumvent insufficient blood-brain barrier (BBB) trafficking and lack of GBM targeting—two major hurdles for anti-GBM therapies. NPs are dual-surface tailored with a i) brain-targeted acid-responsive Angiopep-2 moiety that triggers NP structural rearrangement within BBB endosomal vesicles, and ii) L-Histidine moiety that provides NP preferential accumulation into GBM cells post-BBB crossing. In tumor invasive margin patient cells, the stimuli-responsive multifunctional NPs target GBM cells, enhance cell uptake by 12-fold, and induce three times higher cytotoxicity in 2D and 3D cell models. Moreover, the in vitro BBB permeability is increased by threefold. A biodistribution in vivo trial confirms a threefold enhancement of NP accumulation into the brain. Last, the in vivo antitumor efficacy is validated in GBM orthotopic models following intratumoral and intravenous administration. Median survival and number of long-term survivors are increased by 50%. Altogether, a preclinical proof of concept supports these stimuli-responsive multifunctional NPs as an effective anti-GBM multistage chemotherapeutic strategy, with ability to respond to multiple fronts of the GBM microenvironment.     

RGD-conjugated PLA-PLL nanoparticles targeting to Bacp-37 breast cancer xenografts in vivo

Targeted delivery carriers are receiving considerable attention, the development of a more precise targeted delivery carrier is critical for the advancement of cancer chemotherapy. In this study, we evaluated the effects of RGD-conjugated poly (lactic acid-co-lysine)-(Arginine-Glycine-Aspartic) nanoparticles (PLA-PLL-RGD NPs) on targeted delivery to Bacp-37 breast cancer bearing mice. PLA-PLL-RGD NPs were prepared by using the emulsion-solvent evaporation method. A subsequent MTT assay indicated that the NPs were non-toxic and had good biocompatibility. In vitro, the results of Confocal Laser Scanning Microscope (CLSM) and FAC Scan flow cytometry (FACS) indicated that the PLA-PLL-RGD NPs can bind more significantly to human umbilical vein endothelial cells, compared to PLA-PLL NPs. In vivo, the results of target imaging and biodistribution showed that PLA-PLL-RGD can significantly target to tumor of Bacp-37 breast cancer bearing mice. These results demonstrated that PLA-PLL-RGD NPs can effectively enhance targeted efficiency in vivo, and have the potential to be used as targeted delivery carrier.     

Dynamically PEGylated and Borate‐Coordination‐Polymer‐Coated Polydopamine Nanoparticles for Synergetic Tumor‐Targeted,Chemo‐Photothermal Combination Therapy

Multifunctional nanomaterials with efficient tumor‐targeting and high antitumor activity are highly anticipated in the field of cancer therapy. In this work, a synergetic tumor‐targeted, chemo‐photothermal combined therapeutic nanoplatform based on a dynamically PEGylated, borate‐coordination‐polymer‐coated polydopamine nanoparticle (PDA@CP‐PEG) is developed. PEGylation on the multifunctional nanoparticles is dynamically achieved via the reversible covalent interaction between the surface phenylboronic acid (PBA) group and a catechol‐containing poly(ethylene glycol) (PEG) molecule. Due to the acid‐labile PBA/catechol complex and the weak‐acid‐stable PBA/sialic acid (SA) complex, the nanoparticles can exhibit a synergetic targeting property for the SA‐overexpressed tumor cells, i.e., the PEG‐caused “passive targeting” and PBA‐triggered “active targeting” under the weakly acidic tumor microenvironment. In addition, the photothermal effect of the polydopamine core and the doxorubicin‐loading capacity of the porous coordination polymer layer endow the nanoparticles with the potential for chemo‐photothermal combination therapy. As expected, the in vitro and in vivo studies both verify that the multifunctional nanoparticles possess relatively lower systematic toxicity, efficient tumor targeting ability, and excellent chemo‐photothermal activity for tumor inhibition. It is believed that these multifunctional nanoparticles with synergetic tumor targeting property and combined therapeutic strategies would provide an insight into the design of a high‐efficiency antitumor nanoplatform for potential clinical applications.     

Adriamycin-incorporated nanoparticles of deoxycholic acid-conjugated dextran: antitumor activity against CT26 colon carcinoma

In this study, we prepared adriamycin (ADR)-encapsulated nanoparticles using deoxycholic acid-conjugated dextran (DexDA). Its antitumor activity was evaluated using CT 26 tumor cells in vitro and in vivo. ADR-incorporated DexDA nanoparticles have spherical shapes and their particle sizes were ranged about 50-200. Their particle sizes were changed according to the preparation conditions, i.e., the higher substitution degree (DS) of deoxycholic acid (DA) and higher drug feeding ratio induced increased particle size and zeta potential. Furthermore, the higher DS of DA and higher drug feeding ratio induced increased drug contents and loading efficiency of drug. The higher DS of DA and higher drug feeding ratio induced decreased drug release rate. Futhermore, acidic pH of release media accelerated the drug release rate compared to alkaline pH. At in vitro cytotoxicity test using CT26 tumor cells, the nanoparticles showed higher antitumor activity than free ADR. In fluorescence microscopic observation, nanoparticles were properly entered into tumors cells and maintained in the cells compared to ADR itself. At in vivo animal tumor model using CT-26 cells, nanoparticles resulted in survivability increase of mice even though free ADR showed higher effectiveness to inhibit tumor growth. These results suggested that ADR-incorporated DexDA nanoparticles are promising vehicles for anti-tumor drug delivery.     

Combined Positron Emission Tomography and Cerenkov Luminescence Imaging of Sentinel Lymph Nodes Using PEGylated Radionuclide‐Embedded Gold Nanoparticles

New imaging probes with high sensitivity and stability are urgently needed to accurately detect sentinel lymph nodes (SLNs) for successful cancer diagnosis. Herein, the use of highly sensitive and stable PEGylated radionuclide‐embedded gold nanoparticles (PEG‐RIe‐AuNPs) is reported for the detection of SLNs by combined positron emission tomography and Cerenkov luminescence imaging (PET/CLI). PEG‐RIe‐AuNPs show high sensitivity and stability both in vitro and in vivo, and are not toxic to normal ovarian and immune cells. In vivo PET/CLI imaging clearly reveals SLNs as early as 1 h post PEG‐RIe‐AuNP‐injection, with peak signals achieved at 6 h postinjection, which is consistent with the biodistribution results. Taken together, the data provide strong evidence that PEG‐RIe‐AuNPs are promising as potential lymphatic tracers in biomedical imaging for pre and intraoperative surgical guidance.     

The Crown and the Scepter: Roles of the Protein Corona in Nanomedicine

Engineering nanomaterials are increasingly considered promising and powerful biomedical tools or devices for imaging, drug delivery, and cancer therapies, but few nanomaterials have been tested in clinical trials. This wide gap between bench discoveries and clinical application is mainly due to the limited understanding of the biological identity of nanomaterials. When they are exposed to the human body, nanoparticles inevitably interact with bodily fluids and thereby adsorb hundreds of biomolecules. A “biomolecular corona” forms on the surface of nanomaterials and confers a new biological identity for NPs, which determines the following biological events: cellular uptake, immune response, biodistribution, clearance, and toxicity. A deep and thorough understanding of the biological effects triggered by the protein corona in vivo will speed up their translation to the clinic. To date, nearly all studies have attempted to characterize the components of protein coronas depending on different physiochemical properties of NPs. Herein, recent advances are reviewed in order to better understand the impact of the biological effects of the nanoparticle–corona on nanomedicine applications. The recent development of the impact of protein corona formation on the pharmacokinetics of nanomedicines is also highlighted. Finally, the challenges and opportunities of nanomedicine toward future clinical applications are discussed.     

Investigations on pharmacokinetics and biodistribution of polymeric and solid lipid nanoparticulate systems of atypical antipsychotic drug: effect of material used and surface modification

The present study focuses on the effect of material used for the preparation of nanoparticulate (NP) systems and surface modification on the pharmacokinetics and biodistribution of atypical antipsychotic, olanzapine (OLN). NP carriers of OLN were prepared from two different materials such as polymer (polycaprolactone) and solid lipid (Glyceryl monostearate). These systems were further surface modified with surfactant, Polysorbate 80 and studied for pharmacokinetics–biodistribution in Wistar rats using in-house developed bioanalytical methods. The pharmacokinetics and biodistribution studies resulted in a modified and varied distribution of NP systems with higher area under curve (AUC) values along with prolonged residence time of OLN in the rat blood circulation. The distribution of OLN to the brain was significantly enhanced with surfactant surface-modified NP systems, followed by nonsurface-modified NP formulations as compared with pure OLN solution. Biodistribution study demonstrated a low uptake of obtained NP systems by kidney and heart, thereby decreasing the nephrotoxicity and adverse cardiovascular effects. By coating the NP with surfactant, uptake of macrophage was found to be reduced. Thus, our studies confirmed that the biodistribution OLN could be modified effectively by incorporating in NP drug delivery systems prepared from different materials and surface modifications. A judicious selection of materials used for the preparation of delivery carriers and surface modifications would help to design a most efficient drug delivery system with better therapeutic efficacy.     

Safety profile of two-dimensional Pd nanosheets for photothermal therapy and photoacoustic imaging

Two-dimensional (2D) nanosheets have emerged as an important class of nanomaterial with great potential in the field of biomedicines,particularly in cancer theranostics.However,owing to the lack of effective methods that synthesize uniform 2D nanomaterials with controlled size,systematic evaluation of size-dependent bio-behaviors of 2D nanomaterials is rarely reported.To the best of our knowledge,we are the first to report a systematic evaluation of the influence of size of 2D nanomaterials on their bio-behaviors.2D Pd nanosheets with diameters ranging from 5 to 80 nm were synthesized and tested in cell and animal models to assess their size-dependent bioapplication,biodistribution,elimination,toxicity,and genomic gene expression profiles.Our results showed size significantly influences the biological behaviors of Pd nanosheets,including their photothermal and photoacoustic effects,pharmacokinetics,and toxicity.Compared to larger-sized Pd nanosheets,smaller-sized Pd nanosheets exhibited more advanced photoacoustic imaging and photothermal effects upon ultralow laser irradiation.Moreover,in vivo results indicated that 5-nm Pd nanosheets escape from the reticuloendothelial system with a longer blood half-life and can be cleared by renal excretion,while Pd nanosheets with larger sizes mainly accumulate in the liver and spleen.The 30-nm Pd nanosheets exhibited the highest tumor accumulation.Although Pd nanosheets did not cause any appreciable toxicity at the cellular level,we observed slight lipid accumulation in the liver and inflammation in the spleen.Genomic gene expression analysis showed that 80-nm Pd nanosheets interacted with more cellular components and affected more biological processes in the liver,as compared to 5-nm Pd nanosheets.We believe this work will provide valuable information and insights into the clinical application of 2D Pd nanosheets as nanomedicines.     

Effects of poly (lactic-co-glycolic acid) as a co-emulsifier on the preparation and hypoglycaemic activity of insulin-loaded solid lipid nanoparticles

Poly (lactic-co-glycolic acid) (PLGA) was used as a co-emulsifier in the preparation of insulin-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil as lipid matrix and lecithin as surfactant by doubleemulsion technique. The effects of PLGA on the preparation and hypoglycaemic activity of insulin-loaded SLN were studied. The results showed that with the supplement of PLGA, the encapsulation efficiency and loading capacity were increased significantly from 79.08±1.62 to 85.57±3.21% and 1.58±0.03 to 1.71±0.06%, whereas the surface charge and particle size were changed insignificantly from -25.87±2.65 to -22.67±1.19 mv and 431.0±16.1 to 397.0±68.0 nm, respectively. In vivo studies demonstrated that PLGA increased the sustained hypoglycaemic activity from 12 to 36 h and 24 to 120 h in normal and steptozotocin-induced diabetic mice after a single intramuscular injection of the insulin-loaded SLN. These results demonstrated that PLGA could enhance the entrapment of insulin in the nanoparticles, and more importantly, prolong the time of hypoglycaemic activity of the insulin-loaded SLN.     

Near‐Infrared‐Resonant Gold/Gold Sulfide Nanoparticles as a Photothermal Cancer Therapeutic Agent

The development and optimization of near‐infrared (NIR)‐absorbing nanoparticles for use as photothermal cancer therapeutic agents has been ongoing. This work exploits the properties of gold/gold sulfide NIR‐absorbing nanoparticles (≈35–55 nm) that provide higher absorption (98% absorption and 2% scattering for gold/gold sulfide versus 70% absorption and 30% scattering for gold/silica nanoshells) as well as potentially better tumor penetration. The ability to ablate tumor cells in vitro and efficacy for photothermal cancer therapy is demonstrated, and an in vivo model shows significantly increased long‐term, tumor‐free survival. Furthermore, enhanced circulation and biodistribution is observed in vivo. This class of NIR‐absorbing nanoparticles has the potential to improve upon photothermal tumor ablation for cancer therapy.     

Positive regulation of biochemical parameters by tea polyphenol encapsulated solid lipid nanoparticles at in vitro and in vivo conditions

Tea polyphenols (TPPs) comprise preventive and therapeutic potentials against cancer, cardiovascular and neurological disorders. Chemical instability of TPP which leads to low bioavailability is the major constrain to its use as therapeutic agent. The authors prepared TPP encapsulated solid lipid nanoparticles (TPP‐SLNs) to increase its stability and bioefficacy. Comparison of Fourier transformed infrared spectra of unloaded SLN, free TPP and TPP‐SLN indicated encapsulation of TPP. Sustained release of TPP from TP‐SLN was observed. TPP‐SLN showed prolonged free radical scavenging activity compared with free TPP indicating protection of TPP. TPP‐SLN showed activation of Caspases‐9 and ‐3 cascades in breast cancer cell line (Michigan cancer foundation (MCF)‐7) at in vitro conditions. Biochemical parameters were altered in Ehrlich ascetic carcinoma (EAC) cell bearing mice compared with normal (uninduced) mice which were ameliorated significantly by oral feeding of TPP‐SLN. Oral administration (pre‐ and post‐treated) of TPP‐SLN in EAC bearing mice resulted in significant increase of plasma haemoglobin, glucose, superoxide dismutase and catalase when compared with EAC bearing control mice. Other biochemical parameters (cholesterol, bilirubin, triglyceride, urea, total protein, alanine aminotransferase, alkaline phosphatase and aspertate transaminase were significantly decreased on oral administration (pre‐ and post‐treated) of TPP‐SLN in EAC bearing mice.Inspec keywords: biochemistry, nanomedicine, nanoparticles, free radicals, cancer, enzymes, patient treatmentOther keywords: positive regulation, biochemical parameters, tea polyphenol encapsulated solid lipid nanoparticles, in vitro conditions, in vivo conditions, preventive potentials, therapeutic potentials, cardiovascular disorders, neurological disorders, catalase, superoxide dismutase, glucose, plasma haemoglobin, oral feeding, EAC cell, Ehrlich ascetic carcinoma, MCF‐7, breast cancer cell line, free radical scavenging activity, encapsulation, TPP‐SLN, free TPP, unloaded SLN, Fourier transformed infrared spectra, bioefficacy, therapeutic agent, low bioavailability, chemical instability