Stability In Physiological Media Research Articles

Synthesis and release studies on amylose-based ester prodrugs of fenamic acid NSAIDs.

Aim: To achieve colon-targeted release of mefenamic acid from its ester-linked amylose prodrugs.Materials & methods: The prodrug was characterized by 1H NMR and IR spectroscopy. Drug activation and release profile was studied in enzyme enriched simulated physiological media via UV-vis spectroscopy and was validated with HPLC analysis. ELISA assay was employed for evaluating the % inhibition of COX-1 and COX-2 inhibition at different concentrations of the prodrug preincubated with ester and/ or amylose hydrolyzing enzymes. SEM studies further validated the performance of the prodrug under simulated physiological conditions.Results: Pancreatin was essential for the prodrug activation in SIM to make the ester bonds in prodrug vulnerable to hydrolysis by esterase. This evidence was confirmed by drug release studies, HPLC analysis, ELISA assay and SEM investigation where the ester conjugated prodrug showed marked stability in physiological media only to get activated in the presence of amylose degrading enzyme.Conclusion: Ester linked amylose-mefenamic acid conjugate showed both enzyme responsive activation and release in SIM.

A comparative study of PEO-PBO content on the targeting and anti-glioma activity of annonaceous acetogenins-loaded nanomicelles

Annonaceous acetogenins (ACGs) have great potential in the treatment of gliomas, but are extremely insoluble and difficult for delivery in vivo. Poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO) is an amphiphilic polymer and can reduce the clearance of nanoparticles by mononuclear phagocyte system. To explore an efficient and safe nanomedicine for glioma, ACGs-loaded nanomicelles (ACGs/EB-NCs) was constructed using PEO-PBO as a carrier, and the effect of PEO-PBO content on the targeting and anti-glioma activity were also compared. ACGs/EB5-NCs, ACGs/EB10-NCs and ACGs/EB20-NCs, the three nanomicellels prepared with different ACGs/EB feeding ratios, had average particle sizes of 148.8±0.5 nm, 32.7±4.1 nm, and 27.1±0.3 nm, respectively. The three ACGs/EB-NCs were spherical in shape, with drug loading content close to the theoretical drug loading content, encapsulation efficiency greater than 97 %, and good stability in physiological media. The cumulative release rates of ACGs/EB5-NCs, ACGs/EB10-NCs and ACGs/EB20-NCs were 78.2 %, 63.4 %, and 56.3 % within 216 hours, respectively. The inhibitory effects of three ACGs/EB-NCs on U87 MG cells were similar and stronger than free ACGs (P<0.05), with half inhibitory concentration of 0.17, 0.18, and 0.16 ng/mL (P>0.05), respectively. In U87 MG tumor‑bearing mice, ACGs/EB5-NC, ACGs/EB10-NCs and ACGs/EB20-NCs showed a similar tumor inhibition rate of 61.1±5.9 %, 56.2±8.6 % and 64.3±9.4 % (P>0.05), with good safety. Three ACGs/EB-NCs exhibited excellent liver escape ability and tumor targeting ability, with the tumor targeting index greater than 1.5. Three ACGs/EB-NCs were successfully prepared with strong anti-glioma activity and tumor targeting properties, which are expected to provide new options for the clinical treatment of gliomas. The content of PEO-PBO in micelles did not have a significant effect on the tumor targeting and anti-glioma activity of ACGs/EB-NCs.

Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming

Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces. Specifically, our strategy permits controlled assembly of small poly(β-amino ester)/messenger ribonucleic acid (mRNA) nanoparticles into particles with a size that is kinetically tunable between 200 and 1,000 nm with high colloidal stability in physiological media. We found that assembled particles with an average size of 400 nm safely and most efficiently transfect monocytes following intravenous administration and mediate their differentiation into macrophages in the periphery. When a CpG adjuvant is co-loaded into the particles with an antigen mRNA, the monocytes differentiate into inflammatory dendritic cells and prime adaptive anticancer immunity in the tumor-draining lymph node. This platform technology offers a unique ligand-independent, particle-size-mediated strategy for preferential mRNA delivery and enables therapeutic paradigms via monocyte programming.

Luminescent Alendronic Acid-Conjugated Micellar Nanostructures for Potential Application in the Bone-Targeted Delivery of Cholecalciferol

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV–visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.

Drug-Loaded Polydopamine Nanoparticles for Chemo/Photothermal Therapy against Colorectal Cancer Cells.

Colorectal cancer (CRC) is a common and deadly malignancy, ranking second in terms of mortality and third in terms of incidence on a global scale. The survival rates for CRC patients are unsatisfactory primarily because of the absence of highly effective clinical strategies. The efficacy of existing CRC treatments, such as chemotherapy (CT), is constrained by issues such as drug resistance and damage to healthy tissues. Alternative approaches such as photothermal therapy (PTT), while offering advantages over traditional therapies, suffer instead from a low efficiency in killing tumor cells when used alone. In this context, nanostructures can efficiently contribute to a selective and targeted treatment. Here, we combined CT and PTT by developing a nanoplatform based on polydopamine nanoparticles (PDNPs), selected for their biocompatibility, drug-carrying capabilities, and ability to produce heat upon exposure to near-infrared (NIR) irradiation. As a chemotherapy drug, sorafenib has been selected, a multikinase inhibitor already approved for clinical use. By encapsulating sorafenib in polydopamine nanoparticles (Sor-PDNPs), we were able to successfully improve the drug stability in physiological media and the consequent uptake by CRC cells, thereby increasing its therapeutic effects. Upon NIR stimulus, Sor-PDNPs can induce a temperature increment of about 10 °C, encompassing both PTT and triggering a localized and massive drug release. Sor-PDNPs were tested on healthy colon cells, showing minimal adverse outcomes; conversely, they demonstrated excellent efficacy against CRC cells, with a strong capability to hinder cancer cell proliferation and induce apoptosis. Obtained findings pave the way to new synergistic chemo-photothermal approaches, maximizing the therapeutic outcomes against CRC while minimizing side effects on healthy cells.

Piezoelectric PVDF and its copolymers in biomedicine: innovations and applications.

In recent years, poly(vinylidene fluoride) (PVDF) has emerged as a versatile polymer with a wide range of applications across various fields. PVDF's piezosensitivity, versatility, crystalline structure, and tunable parameters have established it as a highly sought-after material. Furthermore, PVDF and its copolymers exhibit excellent processability and chemical resistance to a diverse array of substances. Of particular significance is its remarkable structural stability in physiological media, which highlights its potential for use in the development of biomedical products. This review offers a comprehensive overview of the latest advancements in PVDF-based biomedical systems. It examines the fabrication of stimulus-responsive delivery systems, bioelectric therapy devices, and tissue-regenerating scaffolds, all of which harness the piezosensitivity of PVDF. Moreover, the potential of PVDF in the fabrication of both invasive and non-invasive diagnostic tools is investigated, with particular emphasis on its flexibility, transparency, and piezoelectric efficiency. The material's high biocompatibility and physiological stability are of paramount importance in the development of implantable sensors for long-term health monitoring, which is crucial for the management of chronic diseases and postoperative care. Additionally,we discuss a novel approach to photoacoustic microscopy that employs a PVDF sensor, thereby eliminating the necessity for external contrast agents. This technique provides a new avenue for non-invasive imaging in biomedical applications. Finally, we explore the challenges and prospects for the development of PVDF-based systems for a range of biomedical applications. This review is distinctive in comparison to other reviews on PVDF due to its concentrated examination of biomedical applications, including pioneering imaging techniques, long-term health monitoring, and a detailed account of advancements in the field. Collectively, these elements illustrate the potential of PVDF to markedly influence biomedical engineering and patient care, distinguishing it from existing literature. By leveraging the distinctive attributes of PVDF and its copolymers, researchers can continue to advance the frontiers of biomedical engineering, with the potential to transform patient care and treatment outcomes.

Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters

Granular polymer hydrogels based on dynamic covalent bonds are attracting a great deal of interest for the design of injectable biomaterials. Such materials generally exhibit shear-thinning behavior and properties of self-healing/recovery after the extrusion that can be modulated through the interactions between gel microparticles. Herein, bulk macro-hydrogels based on thiolated-hyaluronic acid were produced by disulphide bond formation using oxygen as oxidant at physiological conditions and gelation kinetics were monitored. Three different thiol substitution degrees (SD%: 65%, 30% and 10%) were selected for hydrogel formation and fully characterized as to their stability in physiological medium and morphology. Then, extrusion fragmentation technique was applied to obtain hyaluronic acid microgels with dynamic disulphide bonds that were subsequently sterilized by autoclaving. The resulting granular hyaluronic hydrogels were able to form stable filaments when extruded through a syringe. Rheological characterization and cytotoxicity tests allowed to assess the potential of these materials as injectable biomaterials. The application of extrusion fragmentation for the formation of granular hyaluronic hydrogels and the understanding of the relation between the autoclaving processes and the resulting particle size and rheological properties should expand the development of injectable materials for biomedical applications.

Potential and Progress of 2D Materials in Photomedicine for Cancer Treatment.

Over the last decades, photomedicine has made a significant impact and progress in treating superficial cancer. With tremendous efforts many of the technologies have entered clinical trials. Photothermal agents (PTAs) have been considered as emerging candidates for accelerating the outcome from photomedicine based cancer treatment. Besides various inorganic and organic candidates, 2D materials such as graphene, boron nitride, and molybdenum disulfide have shown significant potential for photothermal therapy (PTT). The properties such as high surface area to volume, biocompatibility, stability in physiological media, ease of synthesis and functionalization, and high photothermal conversion efficiency have made 2D nanomaterials wonderful candidates for PTT to treat cancer. The targeting or localized activation could be achieved when PTT is combined with chemotherapies, immunotherapies, or photodynamic therapy (PDT) to provide better outcomes with fewer side effects. Though significant development has been made in the field of phototherapeutic drugs, several challenges have restricted the use of PTT in clinical use and hence they have not yet been tested in large clinical trials. In this review, we attempted to discuss the progress, properties, applications, and challenges of 2D materials in the field of PTT and their application in photomedicine.

Comparative Study of Physicochemical Properties of Alginate Composite Hydrogels Prepared by the Physical Blending and Electrostatic Assembly Methods.

Alginate hydrogel commonly suffers from defects, such as weak mechanical properties, the shortage of long-term stability in physiological medium and the lack of mammalian cell adhesivity due to its strong hydrophilicity in biomedical application. For this reason, the homogeneous alginate hydrogels (Alg Gel) were successfully prepared by the D-glucono-δ-lactone/hydroxyapatite (HAP/GDL) cross-linking system, and then, the physical blending and alternating electrostatic assembly technology were proposed to fabricate alginate composite hydrogels (Alg-GT, Alg-CS-GT and ALG/GT-CS). The feasibility of the design methods was verified through the comparative analysis of their physicochemical properties and biological activity. In particular, the effects of physical blending and alternating electrostatic assembly technology on the pore structure, mechanical properties, swelling, degradation, cell adhesion and proliferation of composite hydrogels were also investigated. Experimental results showed that the formation of polyelectrolyte complexes by electrostatic assembly between biological macromolecules and the covalent cross-linking of EDC/NHS to GT improved the vulnerability of ion cross-linking, enhanced the mechanical properties and swelling stability of the composite hydrogels, and regulated their pore structure and in vitro biodegradability properties. Furthermore, MC3T3-E1 cells could exhibit good cell adhesion, cell viability and cell proliferation on the alginate composite hydrogels. Among them, Alg-CS-GT showed the best cell proliferation ability and differentiation effect due to its good cell adhesion. In view of the excellent physicochemical properties and biological activity of Alg-CS-GT, it exhibited great potential in biomedical application for tissue engineering.

Nanosized magnetite modified with poly(ethylene glycol) for efficient sorption of L-lysine-α-oxidase from the culture fluid

Fe3O4@PEG have been proposed for sorption of L-lysine-α-oxidase (LO) from the culture fluid of Trichoderma harzianum Rifai F-180 for the first time. To synthesize the Fe3O4@PEG nanoparticles, an original method based on aqueous biphasic systems has been developed. The PEG-modified magnetite provide a high sorption ability towards LO in contrast to the non-modified Fe3O4 synthesized by the traditional precipitation method. The morphology and structure of the prepared nanoparticles were characterized by TEM, FTIR and XRD. The data on magnetic properties and stability in physiological media are presented. The synthesized nanoparticles ensure quantitative sorption and desorption of LO during at least 3 cycles.

Surface stabilization determines macrophage uptake, cytotoxicity, and bioactivity of curcumin nanocrystals

Pharmaceutical nanocrystals represent a promising new formulation that combines the benefits of bulk crystalline materials and colloidal nanoparticles. To be applied in vivo, nanocrystals must meet several criteria, namely colloidal stability in physiological media, non-toxicity to healthy cells, avoidance of macrophage clearance, and bioactivity in the target tissue. In the present work, curcumin, a naturally occurring poorly water-soluble molecule with a broad spectrum of bioactivity has been considered a candidate substance for preparing pharmaceutical nanocrystals. Curcumin nanocrystals in the size range of 40–90 nm were prepared by wet milling using the following combination of steric and ionic stabilizers: Tween 80, sodium dodecyl sulfate, Poloxamer 188, hydroxypropyl methylcellulose, phospholipids (with and without polyethylene glycol), and their combination. Nanocrystals stabilized by a combination of phospholipids enriched with polyethylene glycol proved to be the most successful in all evaluated criteria; they were colloidally stable in all media, exhibited low macrophage clearance, and proved non-toxic to healthy cells. This curcumin nanoformulation also exhibited outstanding anticancer potential comparable to commercially used cytostatics (IC50 = 73 µM; 24 h, HT-29 colorectal carcinoma cell line) which represents an improvement of several orders of magnitude when compared to previously studied curcumin formulations. This work shows that the preparation of phospholipid-stabilized nanocrystals allows for the conversion of poorly soluble compounds into a highly effective “solution-like” drug delivery system at pharmaceutically relevant drug concentrations.

Rational surface modification of gadolinium borate nanoparticles enhancing colloidal stability in physiological media for potential neutron capture therapy and magnetic resonance imaging

Colloidal stability of nanomaterials in physiological media is an indispensable property for their biomedical applications. However, gadolinium borate (GdBO3) nanoparticles that hold promise as a theranostic agent for neutron capture therapy (NCT) and magnetic resonance imaging (MRI) of cancer tend to precipitate in phosphate buffered saline (PBS) owing to formation of insoluble gadolinium phosphate. To address this issue, in this work 10B-enriched GdBO3 nanoparticles were prepared and coated with mesoporous silica (mSiO2) of ~ 40 nm in thickness and subsequently grafted with hydrophilic polyglycerol (PG). The resulting GdBO3 @mSiO2-PG nanoparticles showed excellent colloidal stability in PBS due to the protection of the mSiO2 coating as well as superior dispersibility because of the high hydrophilicity of the PG layer. In vitro experiments revealed that GdBO3 @mSiO2-PG possessed low cytotoxicity and could be taken up by cancer cells in a concentration-dependent manner. In vivo studies indicated that GdBO3 @mSiO2-PG can circulate in mouse body for a considerably long time without obvious acute toxicity. In addition, GdBO3 @mSiO2-PG also showed promise as a T1-weighted MRI contrast agent with a proton longitudinal relaxivity of 0.67 mM−1 s−1. Our results indicate that GdBO3 @mSiO2-PG with enhanced colloidal stability in physiological media could serve as a promising multifunctional agent for cancer theranostics.

Rutin-Loaded Stimuli-Responsive Hydrogel for Anti-Inflammation.

An active flavonoid compound rutin was incorporated into a guanosine phenylborate hydrogel (GBR) by a stimuli-responsive borate ester linkage for the treatment of inflammatory bowel disease (IBD). The components and morphology of the drug delivery system were characterized by NMR, UV-vis spectroscopy, and AFM. Rheological measurements revealed the required injectability and self-healing ability, which contributed to its application in rectal administration. The cell assays proved the excellent compatibility and safety of the system, and a possible pathway to form multicellular aggregates. In vitro drug-release studies showed that the hydrogel exhibited good stability in physiological medium, and the drug was almost completely released (more than 90 wt % after 24 h of incubation) in acidic pH and excessive ROS-containing medium, realizing the dual-responsive release of pH/ROS. In vivo activities of the GBR hydrogel showed higher therapeutic efficacy than free rutin in a colitis mice model, and it could significantly inhibit overexpressed inflammatory cytokines, including TNF-α and IL-6. Degradation studies of the hydrogel provided further evidence for the safety of its in vivo application. The work provided a simple strategy to prepare a G-quadruplex drug carrier, which was expected to achieve multi-drug delivery.

Cytotoxicity Assessment of Surface-Modified Magnesium Hydroxide Nanoparticles.

Magnesium-based nanoparticles have shown promise in regenerative therapies in orthopedics and the cardiovascular system. Here, we set out to assess the influence of differently functionalized Mg nanoparticles on the cellular players of wound healing, the first step in the process of tissue regeneration. First, we thoroughly addressed the physicochemical characteristics of magnesium hydroxide nanoparticles, which exhibited low colloidal stability and strong aggregation in cell culture media. To address this matter, magnesium hydroxide nanoparticles underwent surface functionalization by 3-aminopropyltriethoxysilane (APTES), resulting in excellent dispersible properties in ethanol and improved colloidal stability in physiological media. The latter was determined as a concentration- and time-dependent phenomenon. There were no significant effects on THP-1 macrophage viability up to 1.500 μg/mL APTES-coated magnesium hydroxide nanoparticles. Accordingly, increased media pH and Mg2+ concentration, the nanoparticles dissociation products, had no adverse effects on their viability and morphology. HDF, ASCs, and PK84 exhibited the highest, and HUVECs, HPMECs, and THP-1 cells the lowest resistance toward nanoparticle toxic effects. In conclusion, the indicated high magnesium hydroxide nanoparticles biocompatibility suggests them a potential drug delivery vehicle for treating diseases like fibrosis or cancer. If delivered in a targeted manner, cytotoxic nanoparticles could be considered a potential localized and specific prevention strategy for treating highly prevalent diseases like fibrosis or cancer. Looking toward the possible clinical applications, accurate interpretation of in vitro cellular responses is the keystone for the relevant prediction of subsequent in vivo biological effects.

Silica-Based Stimuli-Responsive Systems for Antitumor Drug Delivery and Controlled Release.

The administration of cytotoxic drugs in classical chemotherapy is frequently limited by water solubility, low plasmatic stability, and a myriad of secondary effects associated with their diffusion to healthy tissue. In this sense, novel pharmaceutical forms able to deliver selectively these drugs to the malign cells, and imposing a space-time precise control of their discharge, are needed. In the last two decades, silica nanoparticles have been proposed as safe vehicles for antitumor molecules due to their stability in physiological medium, high surface area and easy functionalization, and good biocompatibility. In this review, we focus on silica-based nanomedicines provided with specific mechanisms for intracellular drug release. According to silica nature (amorphous, mesostructured, and hybrids) nanocarriers responding to a variety of stimuli endogenously (e.g., pH, redox potential, and enzyme activity) or exogenously (e.g., magnetic field, light, temperature, and ultrasound) are proposed. Furthermore, the incorporation of targeting molecules (e.g., monoclonal antibodies) that interact with specific cell membrane receptors allows a selective delivery to cancer cells to be carried out. Eventually, we present some remarks on the most important formulations in the pipeline for clinical approval, and we discuss the most difficult tasks to tackle in the near future, in order to extend the use of these nanomedicines to real patients.

Highly uniform Y3Al2Ga3O12-based nanophosphors for persistent luminescence bioimaging in the visible and NIR regions

A simple strategy is proposed to synthesize highly uniform garnet-based nanospheres that exhibit colloidal stability in physiological media, high biocompatibility and both green and NIR persistent luminescence.

Preparation and Characterization of an Injectable and Photo-Responsive Chitosan Methacrylate/Graphene Oxide Hydrogel: Potential Applications in Bone Tissue Adhesion and Repair.

As life expectancy continues to increase, the inevitable weakening and rupture of bone tissue have grown as concerns in the medical community, thus leading to the need for adhesive materials suitable for bone repair applications. However, current commercially available adhesives face certain drawbacks that prevent proper tissue repair, such as low biocompatibility, poor adhesion to wet surfaces, and the need for high polymerization temperatures. This work aims to develop an injectable and photo-responsive chitosan methacrylate/graphene oxide (ChiMA/GO) adhesive nanocomposite hydrogel of high biocompatibility that is easy to apply by simple extrusion and that offers the possibility for in situ polymer and physiological temperatures. The nanocomposite was thoroughly characterized spectroscopically, microscopically, rheologically, thermally, and through mechanical, textural, and biological assays to fully evaluate its correct synthesis and functionalization and its performance under physiological conditions that mimic those observed in vivo. In addition, a finite element analysis (FEA) simulation was used to evaluate its performance in femur fractures. Results suggest the material’s potential as a bioadhesive, as it can polymerize at room temperature, shows superior stability in physiological media, and is capable of withstanding loads from body weight and movement. Moreover, the material showed remarkable biocompatibility as evidenced by low hemolytic and intermediate platelet aggregation tendencies, and high cytocompatibility when in contact with osteoblasts. The comprehensive studies presented here strongly suggest that the developed hydrogels are promising alternatives to conventional bone adhesives that might be further tested in vivo in the near future.

Synthesis, characterization and biological applications of biofunctional gold nanoparticles for systemic circulation and biological sustainability

Designing nanomaterials for biomedical applications is not a trivial task. Avoidance of the immune system, stability in physiological media, and cell membranes, low toxicity, and optimal bioperformances are critical for the success of the designed nanomaterials. This review focuses on the study of protein-protein and protein-carbohydrates interactions. Most of the biological functions involving biochemical process are closely controlled by protein-protein interactions. Multi-protein complexes perform several catalytic functions. The review also focuses on the in vitro synthesis of bioconjugated nanoparticles and their biological applications such as antimicrobial agents and drug delivery vehicles. The synthesized nanoparticles act as sensor for such interactions. The in vitro synthesis of Au NPs also helps to understand such interactions with better clarity, which are otherwise elusive in the absence of NPs due to their highly complex nature. Both lysozyme (Lys) / Cytochrome, c (Cyt. c) and lysozyme/zein complexes showed remarkable surface adsorption on NP surfaces. The former system produced pH responsive NPs due to its amphiphilic nature and good antimicrobial properties while the latter system produced pH insensitive NPs due to its hydrophobic nature dominated by zein due to presence of non-polar amino acids such as leucine, alanine and proline. Due to insignificant hemolysis both systems may be used as drug delivery vehicles in systemic circulation. The diethylaminoethyl dextran chloride (DEAE) -protein interactions showed that DEAE-BSA and DEAE-Lys mixtures are amphiphilic whereas DEAE-zein mixture is hydrophobic in nature. All different complexes demonstrate strong surface adsorption on both presynthesized Au NPs as well as in vitro synthesis of Au NPs, which leads to the formation of biofunctional Au NPs best suited for biological applications in systemic circulation. The biological applicability is demonstrated from the hemolysis measurements where both DEAE−BSA as well as DEAE−Lys coated Au NPs do not show any marked hemolysis, thus proving to be the best suited vehicles for drug release in systemic circulation. DEAE−zein coated NPs, on the other hand, showed this behavior only in the DEAE rich region of the mixture, but in the protein rich region hemolysis dominates. Copyright © 2017 VBRI Press.

Folic acid-conjugated pH-responsive poly(methacrylic acid) nanospheres for targeted delivery of anticancer drugs to breast cancer cells

Folic acid (FA)-conjugated poly(methacrylic acid) nanospheres were synthesized as a pH-responsive nanocarrier for entrapping doxorubicin (DOX) to target folate-receptors-overexpressing breast cancer cells. To this end, poly(methacrylic acid) nanospheres were first prepared by precipitation polymerization, and then, the FA was conjugated to the pendent hydroxyl groups on the surface of nanospheres via the Stiglich esterification method. The chemical structure of the desired product was evaluated by Fourier transform infrared (FTIR) and hydrogen-nuclear magnetic resonance (1H NMR) techniques. The optimized product had a spherical shape with an average diameter of 149.2 nm and narrow particle size distribution (PDI = 0.268). Also, the surface charge of the prepared nanospheres was measured to be −41.3 mV, indicating a high colloidal stability in physiological media. The prepared nanocarrier displayed a good entrapment efficiency for DOX (86.5%), along with a high drug loading capacity (17.3%). The drug release experiments showed that, by decreasing the pH of the release medium from 7.4 to 5.5, the cumulative release of the DOX from the nanospheres increased from 22 to 32%, indicating the pH-responsivity of the prepared nanocarrier. Moreover, FA-conjugated poly(methacrylic acid) (FA-PMAA) nanospheres showed a higher anticancer efficacy against folate receptor-breast cancer cells (MCF-7 cancer cells) compared to the bare nanospheres and free DOX. The half-maximal inhibitory concentrations (IC50) of free DOX, PMAA, and FA-PMAA nanospheres were 12.8, 11.0, and 2.7 µg/mL, respectively. The obtained results suggest that the FA-PMAA nanospheres could be a promising pH-responsive nanocarrier for the targeted delivery of anticancer drugs to folate-receptor overexpressing cancer cells.

PEGylated Terbium-Based Nanorods as Multimodal Bioimaging Contrast Agents

Diagnostic imaging strongly relies on the use of contrast agents (CAs). In general terms, current CAs present undesirable side effects that encourage researchers and pharmaceutical companies to continually search for safer and more versatile alternatives. Here, we describe the synthesis and characterization of terbium-based nanorods (TbNRs) as a potential alternative to traditional CAs for magnetic resonance imaging (MRI) and X-ray computed tomography (CT). The paramagnetism and high atomic number of Tb provide TbNRs with both magnetic relaxivity and X-ray attenuation capabilities. After surface functionalization with a polyethylene glycol (PEG)-derived ligand, TbNRs showed high colloidal stability in physiological media. Additionally, toxicity studies conducted in cell cultures and zebrafish embryos demonstrated the safety of the as-synthesized TbNRs, thus supporting their potential use as CAs. Lastly, in vivo imaging experiments in mice demonstrated that TbNRs produce remarkable contrast enhancement on both MRI and CT.