Calcium Phosphate Nanoparticles Research Articles

The Remineralizing Effect of Incorporating Ca-Phosphate and Ca-Fluoride Nanoparticles into the Self-Etch Adhesives Used in Restoring Class I Cavities

This study was carried out to investigate the remineralizing effect of amorphous calcium phosphate (ACP) and calcium fluoride (CaF2) nanoparticles incorporated in two-step self etch- adhesives (in vivo). Materials and Methods: The nanoparticles were incorporated into the bond of ClearfilTM SE Bond at a mass fraction of 10%. A total of ten patients in the age range of 17-30 years old, having at least 3 carious lower molars, were enrolled in this study (split mouth design). Class I cavity preparation was performed, leaving the caries affected dentine at the pulpal floor. The 30 molars were divided into 3 groups (n=10) according to the type of adhesive used (A); namely: self-etch adhesive, Clearfil SE Bond (Control)(A1), Clear Fill SE Bond incorporated with ACP NPs (A2) and Clearfil SE Bond incorporated with CaF2 NPs (A3). After restoration placement, each tooth was radiographically evaluated at baseline (I0), after 1 month (I1) and after 3 months (I2) to assess the remineralizing effect of the adhesive systems used. Results: The adhesive containing ACP nanoparticles induced the highest remineralization potential during all the study intervals, followed by the adhesive containing (CaF2) nanoparticles. Conclusion: nanoparticles are capable of remineralizing the caries affected dentin when incorporated into two-step self etch adhesive

Chlorogenic acid- loaded calcium phosphate chitosan nanogel as biofilm degradative materials

This work describes an effort to develop an antimicrobial agent (chlorogenic acid - CGA) loaded porous nanogel based on calcium phosphate-chitosan (CaPNP@Chi) nanogel with biofilm degradative properties and has potential applications in restorative dentistry. The nanogel was prepared by ionic gelation of calcium phosphate nanoparticles and chitosan in the ratio of 1.25: 1. Chlorogenic acid was loaded to the nanoparticles as an ethanolic solution and the encapsulation efficiency determined by chromatographic techniques. The particle size and morphology of CaPNP@Chi and CaPNP@Chi@CGA was determined by dynamic light scattering and scanning electron microscopic techniques. The minimum inhibitory concentration against S. aureus and K. pneumoniae was determined through the well diffusion method. The biofilm formation and biofilm decay were studied through staining assays. The toxicity, if any of the nanogel was assessed by MTT assay against HaCaT cells. All data were statistically analyzed. The composite had a CGA encapsulation efficiency of 70% and was thermally stable up to 124 °C. The zone of inhibition was found to be 18.7 mm ± 0.6 against S. aureus. CaPNP@Chi@CGA showed a 68% increase in biofilm degradation when compared with the untreated group. Results obtained in this study suggest that the positively charged nanogel interacted with the bacterial cell membrane and brought about the disruption of the cell membrane. Also, CaPNP@Chi@CGA was observed to be nontoxic up to 40 μg/mL to HaCaT cells. These results support the potential of CaPNP@Chi@CGA nanogel for biofilm degradation and its application as filling material in restorative dentistry.

Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles

Despite many years of research and a few success stories with gene therapeutics, efficient and safe DNA delivery remains a major bottleneck for the clinical translation of gene-based therapies. Gene transfection with calcium phosphate (CaP) nanoparticles brings the advantages of low toxicity, high DNA entrapment efficiency and good endosomal escape properties. The macroscale aggregation of CaP nanoparticles can be easily prevented through surface coating with bisphosphonate conjugates. Bisphosphonates, such as alendronate, recently showed promising anticancer effects. However, their poor cellular permeability and preferential bone accumulation hamper their full application in chemotherapy. Here, we investigated the dual delivery of plasmid DNA and alendronate using CaP nanoparticles, with the goal to facilitate cellular internalization of both compounds and potentially achieve a combined pharmacological effect on the same or different cell lines. A pH-sensitive poly(ethylene glycol)-alendronate conjugate was synthetized and used to formulate stable plasmid DNA-loaded CaP nanoparticles. These particles displayed good transfection efficiency in cancer cells and a strong cytotoxic effect on macrophages. The in vivo transfection efficiency, however, remained low, calling for an improvement of the system, possibly with respect to the extent of particle uptake and their physical stability.

Bone Mineral Crystallinity Governs the Orchestration of Ossification and Resorption during Bone Remodeling.

The circularly causal orchestration of bone production and destruction is a part of the standard model of bone remodeling, but the crystallinity of the bone mineral, which naturally alternates during this process, has not had a steady place in it. Here we show that osteoclasts and osteoblasts, the cells resorbing and building bone, respectively, can sense the crystallinity of the bone mineral and adjust their activity thereto. Specifically, osteoblastic MC3T3-E1 cells secreted mineral nodules more copiously when they were brought into contact with amorphous calcium phosphate (ACP) nanoparticles than when they were challenged with their crystalline, hydroxyapatite (HAp) analogues. Moreover, the gene expressions of osteogenic markers BGLAP, ALP, BSP-1, and RUNX2 in MC3T3-E1 cells were higher in the presence of ACP than in the presence of HAp. At the same time, the dental pulp stem cells differentiated into an osteoblastic phenotype to a degree that was inversely proportional to the amount and the crystallinity of the mineral added to their cultures. In contrast, the resorption of HAp nanoparticles was more intense than the resorption of ACP, as concluded by the greater retention of the latter particles inside the osteoclastic RAW264.7 cells after 10 days of incubation and also by the time-dependent free Ca2+ concentration measurements in the cell culture media at early incubation time points (<1 week), prior to the spontaneous crystallization of the amorphous phase. A detailed morphological, compositional, and microstructural characterization of ACP and HAp is provided too, and it is shown that although ACP transforms to HAp in the cell culture media, some microstructural properties are retained in the powder following this transformation, influencing the resorption rate. On the basis of these findings, a model of bone remodeling at the level of individual biogenic apatite nanoparticles was proposed, taking into account the effects of hydration and lattice strain. According to this model, apatite is a "living" mineral, undergoing fluctuations in crystallinity within a closed ossifying/resorptive feedback loop in a way that buffers against potential runaway effects. A finite degree of amorphousness of every apatite crystal in bone is seen as a vital prerequisite for a healthy, dynamic bone remodeling process, and the best bone mineral, from this standpoint, is the living mineral, the one undergoing a constant process of structural change in response to biochemical stimuli thanks to its partially amorphous microstructure and unique interfacial dynamics.

Biofabrication of streptomycin-conjugated calcium phosphate nanoparticles using red ginseng extract and investigation of their antibacterial potential.

Conjugation of nanoparticles (NPs) with antibiotics for treating multidrug resistant pathogens has been enormously studied now a days. In the current investigation, calcium phosphate (CaP) NPs were produced by co-precipitation using red ginseng extract as the reducing agent and were conjugated to the antibiotic streptomycin to form streptomycin-conjugated NPs (CPG-S NPs). The CPG-S NPs antibacterial activity was evaluated in this study against eight plant and five foodborne pathogenic bacteria. The synthesized CPG-S NPs were characterized by UV-VIS spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, and thermogravimetric and differential thermogravimetric analysis. CPG-S NPs exhibited promising antibacterial activity against all eight plant pathogenic bacteria and three of the five foodborne pathogenic bacteria tested; the diameter of inhibition zones ranged between 9.74–16.95 mm and 9.82–15.84 mm, respectively. CPG-S NPs displayed 50–100 μg/mL of minimum inhibitory concentration and 100 μg/mL of minimum bactericidal concentration against the plant and foodborne pathogenic bacterial strains, respectively. Furthermore, the SEM image of bacteria treated with CPG-S NPs displayed cells with a ruptured cell wall and fewer cells compared to the SEM image of untreated control bacteria displaying uniform and intact cells. SEM confirmed that CPG-S NPs degraded the bacterial cell wall and membrane resulting in lysed bacterial cells. In conclusion, the results suggest that CPG-S NPs could be effectively utilized in formulating drugs to treat bacterial plant or dental diseases and in manufacturing dental products such as toothpaste, mouthwashes, and artificial teeth.

Positive impact of dynamic seeding of mesenchymal stem cells on bone-like biodegradable scaffolds with increased content of calcium phosphate nanoparticles.

One of the main aims of bone tissue engineering, regenerative medicine and cell therapy is development of an optimal artificial environment (scaffold) that can trigger a favorable response within the host tissue, it is well colonized by resident cells of organism and ideally, it can be in vitro pre-colonized by cells of interest to intensify the process of tissue regeneration. The aim of this study was to develop an effective tool for regenerative medicine, which combines the optimal bone-like scaffold and colonization technique suitable for cell application. Accordingly, this study includes material (physical, chemical and structural) and in vitro biological evaluation of scaffolds prior to in vivo study. Thus, porosity, permeability or elasticity of two types of bone-like scaffolds differing in the ratio of collagen type I and natural calcium phosphate nanoparticles (bCaP) were determined, then analyzes of scaffold interaction with mesenchymal stem cells (MSCs) were performed. Simultaneously, dynamic seeding using a perfusion bioreactor followed by static cultivation was compared with standard static cultivation for the whole period of cultivation. In summary, cell colonization ability was estimated by determination of cell distribution within the scaffold (number, depth and homogeneity), matrix metalloproteinase activity and gene expression analysis of signaling molecules and differentiation markers. Results showed, the used dynamic colonization technique together with the newly-developed collagen-based scaffold with high content of bCaP to be an effective combined tool for producing bone grafts for bone implantology and regenerative medicine.

Thermally Modified Iron-Inserted Calcium Phosphate for Magnetic Hyperthermia in an Acceptable Alternating Magnetic Field.

Magnetic hyperthermia treatment using calcium phosphate nanoparticles is an evolutionary choice because of its excellent biocompatibility. In the present work, Fe3+ is incorporated into HAp nanoparticles by thermal treatment at various temperatures. Induction heating was examined within the threshold H f value of 4.58 × 106 kA m-1 s-1 (H is the strength of alternating magnetic field and f is the operating frequency) and sample concentration of 10 mg/mL. The temperature-dependent structural modifications are well correlated with the morphological, surface charge, and magnetic properties. Surface charge changes from +10 mV to -11 mV upon sintering because of the diffusion of iron in the HAp lattice. The saturation magnetization has been achieved by sintering the nanoparticles at 400 and 600 °C, which has led to the specific absorption rate of 12.2 and 37.2 W/g, respectively. Achievement of the hyperthermia temperature (42 °C) within 4 min is significant when compared with the existing magnetic calcium phosphate nanoparticles. The systematic investigation reveals that the HAp nanoparticles partially stabilized with FeOOH and biocompatible α-Fe2O3 exhibit excellent induction heating. In vitro tests confirmed the samples are highly hemocompatible. The importance of the present work lies in HAp nanoparticles exhibiting induction heating without compromising the factors such as H f value, low sample concentration, and reduced duration of applied field.

Theranostic Calcium Phosphate Nanoparticles With Potential for Multimodal Imaging and Drug Delivery.

Calcium phosphate (CaP) bioceramics closely resemble the natural human bone, which is a main reason for their popularity as bone substitutes. However, this compositional similarity makes it difficult to distinguish CaPs, especially in particulate form, from native bone by imaging modalities such as X-ray radiography, computed tomography (CT), and magnetic resonance imaging (MRI) to monitor the healing progress. External contrast agents can improve the imaging contrast of CaPs but can affect their physicochemical properties and can produce artifacts. In this work, we have attempted to improve the contrast of CaP nanoparticles via ion substitutions for multimodal imaging. Calcium-deficient hydroxyapatite (CDHA) nanoparticles with silver (Ag), gadolinium (Gd), and iron (Fe) substitution were prepared by a microwave-accelerated wet chemical process to improve the contrast in CT, T1 (spin–lattice), and T2 (spin–spin) MRI relaxation modes, respectively. Ag, Gd, and Fe were substituted at 0.25, 0.5, and 0.25 at.%, respectively. The ion-substituted CDHA (ICDHA) was found to be phase pure by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Transmission electron microscopy (TEM) images showed that the ICDHA nanoparticles were platelet shaped and of 52 ± 2 nm length and 6 ± 1 nm width. The ICDHA showed high contrast in X-ray and CT compared to CDHA. The vibrating sample magnetometry (VSM) studies showed the ICDHA to exhibit paramagnetic behavior compared to diamagnetic CDHA, which was further confirmed by improved contrast in T1 and T2 MRI mode. In addition, the in vitro tetracycline drug loading and release was studied to investigate the capability of these nanoparticles for antibiotic drug delivery. It was found that a burst release profile was observed for 24 h with 47–52% tetracycline drug release. The ICDHA nanoparticles also showed in vitro antibacterial activity against Staphylococcus aureus and Escherichia coli due to Ag, which was further enhanced by antibiotic loading. In vitro biocompatibility studies showed that the triple-ion-substituted ICDHA nanoparticles were cytocompatible. Thus, the ion-substituted CDHA nanoparticles can have potential theranostic applications due to their multimodal image contrast, antibacterial activity, and drug delivery potential. Future work will be conducted with actual bone samples in vitro or in animal models.

A Tumor-Peptide-Based Nanoparticle Vaccine Elicits Efficient Tumor Growth Control in Antitumor Immunotherapy.

Recognition of immunoactive oligonucleotides by the immune system, such as Toll-like receptor ligand CpG, leads to increased antibody and T-cell responses. Systemic application often results in unwanted generalized nonantigen-specific activation of the immune system. Nanoparticles are ideal carriers for small and large molecules. Recently, we have demonstrated that calcium phosphate (CaP) nanoparticles functionalized with CpG, and viral antigens are able to induce specific T-cell immunity that protects mice against viral infection and efficiently reactivates the exhausted CD8+ T-cell compartment during chronic retroviral infection. Therefore, CaP nanoparticles are promising vaccine vehicles for therapeutic applications. In this study, we investigated the therapeutic potential use of these nanoparticles in a murine xenograft colorectal cancer model. Therapeutic vaccination with CaP nanoparticles functionalized with CpG and tumor model antigens increased the frequencies of cytotoxic CD8+ T cells in the tumor in a type I interferon-dependent manner. This was accompanied with significantly repressed tumor growth in contrast to the systemic administration of soluble CpG and antigens. Combination therapy of CaP nanoparticles and immune checkpoint blocker against PD-L1 further enhanced the cytotoxic CD8+ T-cell response and eradicated the tumors. Strikingly, vaccination with CaP nanoparticles functionalized with CpG and a primary tumor cell lysate was also sufficient to control the tumor growth. In conclusion, our results represent a translational approach for the use of CaP nanoparticles as a potent cancer vaccine vehicle.

Multifunctional lipid-coated calcium phosphate nanoplatforms for complete inhibition of large triple negative breast cancer via targeted combined therapy

Combined and targeted therapy have been extensively employed to achieve more effective elimination of tumor tissues. In this study, biocompatible multifunctional lipid-coated calcium phosphate nanoparticles (LCP NPs) were designed and constructed as an efficient targeted delivery system for combined gene/photothermal therapy to inhibit growth of the triple negative breast tumor (MDA-MB-468) in vitro and in vivo. LCP NPs were functionalized with a bispecific antibody (BsAb) via non-covalent bond specific for methoxy group of PEG (mPEG) on the particle surface. This BsAb is also able to target epidermal growth factor receptor (EGFR) expressed on MDA-MB-468 cells. Such LCP-BsAb NPs loaded with Cell Death (CD)-siRNA and indocyanine green (ICG) were efficiently taken up by MDA-MB-468 cells, significantly inducing cell apoptosis and synergistically suppressing cell proliferation upon irradiation of 808 nm near-infrared laser. These targeted multifunctional LCP NPs more efficiently accumulated in the tumor tissue. The combined RNAi (CD-siRNA) and photothermal (ICG) therapy using the targeted LCP NPs nearly eliminated both small tumors (∼100 mm3) and large tumors (∼500 mm3) in the mouse model. Thus, the well-devised multifunctional LCP NPs are one of the most promising delivery systems for combined and targeted cancer therapy.

Self-healing adhesive with antibacterial activity in water-aging for 12 months

ObjectiveSecondary caries and micro-cracks are the main limiting factors for dentin bond durability. The objectives of this study were to develop a self-healing adhesive containing dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP), and investigate the effects of water-aging for 12 months on self-healing, dentin bonding, and antibacterial properties for the first time. MethodsMicrocapsules were synthesized with poly (urea-formaldehyde) (PUF) shells containing triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT). The adhesive contained 7.5% microcapsules, 10% DMAHDM, and 20% NACP (all mass). Specimens were water-aged at 37 °C for 1 day to 12 months. Dentin bond strength was measured using extracted human teeth. A single-edge-V-notched-beam (SEVNB) method was used to measure fracture toughness KIC and self-healing efficiency. A dental plaque microcosm biofilm model was used with human saliva as inoculum. ResultsThe microcapsules + DMAHDM + NACP group showed no decline in dentin bond strength after water-aging for 12 months, which was significantly higher than that of other groups without DMAHDM (p < 0.05). A self-healing efficiency of 67% recovery in KIC was obtained even after 12 months of water immersion, indicating that the self-healing ability was not lost in water-aging (p > 0.1). The bacteria-killing ability of this adhesive did not decline from 1 day to 12 months (p > 0.1), with biofilm CFU reduction by 3–4 orders of magnitude after the resin was water-aged for 12 months, compared to control resin. SignificanceThis novel adhesive with triple merits of self-healing, antibacterial and remineralization functions showed an excellent long-term durability in water-aging for 12 months. This multifunctional adhesive has the potential for dental applications to heal cracks, inhibit bacteria, provide ions for remineralization, and increase the restoration longevity.

Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: In search of the key particle property.

One of the main goals of materials science in the 21st century is the development of materials with rationally designed properties as substitutes for traditional pharmacotherapies. At the same time, there is a lack of understanding of the exact material properties that induce therapeutic effects in biological systems, which limits their rational optimization for the related medical applications. This study sets the foundation for a general approach for elucidating nanoparticle properties as determinants of antibacterial activity, with a particular focus on calcium phosphate nanoparticles. To that end, nine physicochemical effects were studied and a number of them were refuted, thus putting an end to frequently erred hypotheses in the literature. Rather than having one key particle property responsible for eliciting the antibacterial effect, a complex synergy of factors is shown to be at work, including (a) nanoscopic size; (b) elevated intracellular free calcium levels due to nanoparticle solubility; (c) diffusivity and favorable electrostatic properties of the nanoparticle surface, primarily low net charge and high charge density; and (d) the dynamics of perpetual exchange of ultrafine clusters across the particle/solution interface. On the positive side, this multifaceted mechanism is less prone to induce bacterial resistance to the therapy and can be a gateway to the sphere of personalized medicine. On a more problematic side, it implies a less intense effect compared to single-target molecular therapies and a difficulty of elucidating the exact mechanisms of action, while also making the rational design of theirs for this type of medical application a challenge.

Extracellular calcium-phosphate nanoparticles activate the NLRP3 inflammasome through CaSR signaling

Abstract Calcium and phosphate are well known as the main minerals in bone ossification. But they also have an immunomodulatory potential as components of calciprotein particles. Such particles precipitate spontaneously in body fluids if the calcium and phosphate homeostasis is disturbed. An abnormally increased mineral load could lead to soft tissue calcification. In our study we investigated the cellular response of freshly isolated peripheral blood monocytes in serum-containing medium under precipitating (high calcium and high phosphate content) conditions. Using dynamic mass redistribution analyses with the EPIC® system and IL-1β measurements as readout, we identified phosphate as a necessary co-modulator of calcium-triggered overall cellular responses and NLRP3 inflammasome activation. Moreover, flow cytometry and ImageStream® analyses revealed the uptake of spontaneously formed nanoparticles under stimulating conditions, which depends on the activation of the G protein-coupled receptor Calcium-sensing receptor (CaSR). Our study unraveled a GPCR-mediated mechanism by which monocytes detect imbalances in calcium phosphate homeostasis in the extracellular space resulting in an enormous pro-inflammatory cellular response.

Poly(amido amine) and rechargeable adhesive containing calcium phosphate nanoparticles for long-term dentin remineralization

ObjectivesThe objective of the present study was to investigate long-term dentin remineralization via the combination of poly(amido amine) (PAMAM) with a novel rechargeable adhesive containing nanoparticles of amorphous calcium phosphate (NACP). MethodsThe NACP adhesive was immersed in lactic acid at pH 4 to exhaust its calcium (Ca) and phosphate (P) ion release, and then recharged with Ca and P ions. Dentin samples were pre-demineralized with 37% phosphoric acid, and then divided into four groups: (1) dentin control, (2) dentin treated with PAMAM, (3) dentin with recharged NACP adhesive, (4) dentin with PAMAM + recharged NACP adhesive. In group (2) and (4), the PAMAM-coated dentin was immersed in phosphate-buffered saline with vigorous shaking for 77 days to accelerate any detachment of the PAMAM macromolecules from the demineralized dentin. Samples were treated with a cyclic remineralization/demineralization regimen for 21 days. ResultsAfter 77 days of fluid flow challenge, the immersed PAMAM still retained its nucleation template function. The recharged NACP adhesive possessed sustained ion re-release and acid-neutralization capability, both of which did not decrease with repeated recharge and re-release cycles. The immersed PAMAM with the recharged NACP adhesive achieved long-term dentin remineralization, and restored dentin hardness to that of healthy dentin. ConclusionsThe PAMAM + NACP adhesive completely remineralizes pre-demineralized dentin even after long-term fluid challenges and provides long-term remineralization to protect tooth structures. Clinical significanceThe novel PAMAM + NACP adhesive provides long-term bond protection and caries inhibition to increase the longevity of resin-based restorations.

Design and development of bioinspired calcium phosphate nanoparticles of MTX: pharmacodynamic and pharmacokinetic evaluation

The aim of this investigation is the management of rheumatoid arthritis (RA) by developing methotrexate-loaded calcium phosphate nanoparticles (MTX-CAP-NP) and to evaluate pharmacokinetic and pharmacodynamic behavior in adjuvant induced arthritis model. The nanoparticles were synthesized by wet precipitation method and optimized by Box-Behnken experimental design. MTX-CAP-NPs were characterized by TEM, FTIR, DSC and XRD studies. The particle size, zeta potential and entrapment efficiency of the optimized nanoparticles were found to be 204.90 ± 64 nm, −11.58 ± 4.80 mV, and 88.33 ± 3.74%, respectively. TEM, FTIR, DSC and XRD studies revealed that the developed nanoparticles were nearly spherical in shape and the crystalline structure of CAP-NP was not changed after MTX loading. The pharmacokinetic studies revealed that MTX-CAP-NP enhanced bioavailability of MTX by 2.6-fold when compared to marketed formulation (FOLITRAX-10). Under pharmacodynamic evaluation, arthritic assessment, radiography and histopathology studies revealed that CAP has ability to regenerate cartilage and bone therefore, together with MTX, MTX-CAP-NPs have shown significant reduction in disease progression. The overall work demonstrated that the developed nanodelivery system was well tolerated and more effective than the marketed formulation.

Development, Characterization and In Vitro Biological Properties of Scaffolds Fabricated From Calcium Phosphate Nanoparticles.

Ceramic materials mimic the mineral composition of native bone and feature osteoconductive properties; they are therefore used to regenerate bone tissue. Much research focuses on increasing the porosity and pore interconnectivity of ceramic scaffolds to increase osteoconductivity, cell migration and cell-cell interaction. We aimed to fabricate biocompatible 3D-scaffolds featuring macro- and microporous calcium phosphates with high pore interconnection. Nanoparticles of hydroxyapatite (HA) and calcium deficient hydroxyapatite (CDHA) were synthesized by wet chemical precipitation. Scaffolds were produced from them by the replication polymeric foam technique. Solid content and sintering temperature were varied. Nanoparticles and scaffolds were characterized regarding morphology, chemical and mineral composition, porosity and mechanical properties. Biocompatibility, cell attachment and distribution were evaluated in vitro with human adipose mesenchymal stem cells. Scaffolds with total porosity of 71%–87%, pores in the range of 280–550 µm and connectivity density up to 43 mm−3 were obtained. Smaller pore sizes were obtained at higher sintering temperature. High solid content resulted in a decrease of total porosity but increased interconnectivity. Scaffolds 50HA/50β-TCP featured superior interconnectivity and mechanical properties. They were bioactive and biocompatible. High HA solid content (40 wt.%) in the HA pure scaffolds was negative for cell viability and proliferation, while in the 50HA/50β-TCP composite scaffolds it resulted more biocompatible.

PH responsive delivery of lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes for the site specific treatment of lung cancer

The present work aim to develop pH responsive nanosystem comprising lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes for the effective treatment of lung cancer. FTIR results showed that, compatibility nature of selected excipients for the synthesis of LF-CaP-Cs. The XRD results showed developed LF-CaP-Cs were non crystalline in nature. The selected developed LF-CaP-Cs were in cubic phase with average particle size of 259.4 ± 19 nm with a charge of -2.28 ± 0.7 mV. The encapsulation efficiency for LF within LF-CaP-Cs was about 78.76 ± 0.5%. RP-HPLC analysis showed that LF release rate gets significantly enhanced with higher peak area at pH 4.0 compared to pH 5.0/pH 7.4. The in-vitro release of LF-CaP-Cs showed that LF release gets significantly increased at pH 4.0 (84.04 ± 0.4%) compared to pH 7.4 (48.32 ± 1.6%) at 12 h. Further, CAM assay showed the superior anti-angiogenesis potential of developed LF-CaP-Cs compared to LF-Cs/blank Cs. The cytotoxicity effect of LF-CaP-Cs (28 ± 1.8 μg/mL) was significantly higher than that of free LF (40 ± 0.9 μg/mL). The results of cellular uptake study proved the localization of LF at cellular level and AO/EB staining results revealed that the A549 cell undergoes apoptosis in A549 cells.

Nanofibrous hydroxyapatite composed of nanoparticles fabricated by electrospinning

Nanofibrous hydroxyapatite (HAp) composed of nanoparticles was successfully fabricated by assembling amorphous calcium phosphate (ACP) nanoparticles with poly(vinyl alcohol) (PVA) by electrospinning. ACP-PVA nanofibers were obtained by electrospinning. A nanofibrous HAp was fabricated by calcination of the ACP-PVA nanofibers, and the obtained HAp nanofibers were composed of nanoparticles and had nanopores. The concentrations of ACP and the PVA binder in the spinning solution affected the morphology of the obtained nanofibrous HAp structure; rodlike, meshlike, and fiberlike structures were obtained by adjusting the concentrations.

The Remineralizing Effect of Incorporating Ca-Phosphate and Ca-Fluoride Nanoparticles into the Self-Etch Adhesives Used in Restoring Class I Cavities

This study was carried out to investigate the remineralizing effect of amorphous calcium phosphate (ACP) and calcium fluoride (CaF2) nanoparticles incorporated in two-step self etch- adhesives (in vivo). Materials and Methods: The nanoparticles were incorporated into the bond of ClearfilTM SE Bond at a mass fraction of 10%. A total of ten patients in the age range of 17-30 years old, having at least 3 carious lower molars, were enrolled in this study (split mouth design). Class I cavity preparation was performed, leaving the caries affected dentine at the pulpal floor. The 30 molars were divided into 3 groups (n=10) according to the type of adhesive used (A); namely: self-etch adhesive, Clearfil SE Bond (Control)(A1), Clear Fill SE Bond incorporated with ACP NPs (A2) and Clearfil SE Bond incorporated with CaF2 NPs (A3). After restoration placement, each tooth was radiographically evaluated at baseline (I0), after 1 month (I1) and after 3 months (I2) to assess the remineralizing effect of the adhesive systems used. Results: The adhesive containing ACP nanoparticles induced the highest remineralization potential during all the study intervals, followed by the adhesive containing (CaF2) nanoparticles. Conclusion: nanoparticles are capable of remineralizing the caries affected dentin when incorporated into two-step self etch adhesive

In situ Fabrication of Biological Chitosan and Gelatin-Based Hydrogels Loading Biphasic Calcium Phosphate Nanoparticles for Bone Tissue Regeneration

Adjustably biodegradable materials have gained much attention in biomedical applications. Among of them, various hydrogel-based scaffolds have applied for regenerating soft and hard tissues. In this study, according to differently biological properties of gelatin or chitosan as well as biphasic calcium phosphate nanoparticles (BCPNPs), several injectable nanocomposite hydrogels (INgel) were enzymatically fabricated from a phenolic chitosan derivative (PCD), phenolic gelatin derivative (PGD) and BCPNPs. According the change of H2O2 concentration with follow-up the time, the in situ formation of INgel was varied from 35 to 80 s. The degradation rate of the nanocomposite materials significantly related to in presence of collagenase that expended from 3 days to over one month depending on amount of the formulated PCD. The BCPNPs-encapsulated PCD-PGD INgel enhanced mineralization in the simulated biofluid. Fluorescent cytotoxicity assay indicated that the INgel was fabricated from a higher amount of the PGD resulting in a significant proliferation of bone marrow mesenchymal stem cells. These preliminary results exhibited a great potential of the INgel for bone regeneration.