CaP Nanoparticles Research Articles

Periostin-targeted SDSSD peptide decorated calcium phosphate nanocomposites incorporation with simvastatin for osteoporosis treatment

The limited options of anabolic drugs restrict their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Sim in vivo. Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.

Calcium Orthophosphate in Liposomes for Co-Delivery of Doxorubicin Hydrochloride/Paclitaxel in Breast Cancer.

Nanoparticles (NPs) show great advantages in cancer treatment by enabling controlled and targeted delivery of payloads to tumor sites through the enhanced permeability and retention (EPR) effect. In this study, highly effective pH-responsive and biodegradable calcium orthophosphate@liposomes (CaP@Lip) NPs with a diameter of 110 ± 20 nm were designed and fabricated. CaP@Lip NPs loaded with hydrophobic paclitaxel and hydrophilic doxorubicin hydrochloride achieved excellent drug loading efficiencies of 70 and 90%, respectively. Under physiological conditions, the obtained NPs are negatively charged. However, they switched to positively charged when exposed to weak acidic environments by which internalization can be promoted. Furthermore, the CaP@Lip NPs exhibit an obvious structural collapse under acid conditions (pH 5.5), which confirms their excellent biodegradability. The "proton expansion" effect in endosomes and the pH-responsiveness of the NPs facilitate the release of encapsulated drugs from individual channels. The effectiveness and safety of the drug delivery systems were demonstrated through in vitro and in vivo experiments, with a 76% inhibition of tumor growth. These findings highlight the high targeting ability of the drug-loaded NPs to tumor sites through the EPR effect, effectively suppressing tumor growth and metastasis. By combining CaP NPs and liposomes, this study not only resolves the toxicity of CaP but also enhances the stability of liposomes. The CaP@Lip NPs developed in this study have significant implications for biomedical applications and inspire the development of intelligent and smart drug nanocarriers and release systems for clinical use.

Plant growth promoting potential of urea doped calcium phosphate nanoparticles in finger millet (Eleusine coracana (L.) Gaertn.) under drought stress.

Drought is a leading threat that impinges on plant growth and productivity. Nanotechnology is considered an adequate tool for resolving various environmental issues by offering avant-garde and pragmatic solutions. Using nutrients in the nano-scale including CaP-U NPs is a novel fertilization strategy for crops. The present study was conducted to develop and utilize environment-friendly urea nanoparticles (NPs) based nano-fertilizers as a crop nutrient. The high solubility of urea molecules was controlled by integrating them with a matrix of calcium phosphate nanoparticles (CaP NPs). CaP NPs contain high phosphorous and outstanding biocompatibility. Scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and X-ray diffraction analysis (XRD) were used to characterize the fabricated NPs. FE-SEM determined no areas of phase separation in urea and calcium phosphate, indicating the successful formation of an encapsulated nanocomposite between the two nano matrices. TEM examination confirmed a fiber-like structure of CaP-U NPs with 15 to 50 nm diameter and 100 to 200 nm length. The synthesized CaP-U NPs and bulk urea (0.0, 0.1% and 0.5%) were applied by foliar sprays at an interval of 15 days on pre-sowed VL-379 variety of finger millet (Eleusine coracana (L.) Gaertn.), under irrigated and drought conditions. The application of the CaP-U NPs significantly enhanced different plant growth attributes such as shoot length (29.4 & 41%), root length (46.4 & 51%), shoot fresh (33.6 & 55.8%) and dry weight (63 & 59.1%), and root fresh (57 & 61%) and dry weight (78 & 80.7%), improved pigment system (chlorophyll) and activated plant defense enzymes such as proline (35.4%), superoxide dismutase (47.7%), guaiacol peroxidase (30.2%), ascorbate peroxidase (70%) under both irrigated and drought conditions. Superimposition of five treatment combinations on drought suggested that CaP-U NPs at 0.5 followed by 0.1% provided the highest growth indices and defense-related enzymes, which were significantly different. Overall, our findings suggested that synthesized CaP-U NPs treatment of finger millet seeds improved plant growth and enzymatic regulation, particularly more in drought conditions providing insight into the strategy for not only finger millet but probably for other commercial cereals crops which suffer from fluctuating environmental conditions.

Cover Feature: Methionine Capped Nanoparticles as Acetylcholinesterase Inhibitors (Eur. J. Inorg. Chem. 12/2023)

The Cover Feature shows a metal nanoparticle modified with the amino acid L-methionine and the adsorption of the enzyme acetylcholinesterase (AChE) on the methionine-capped nanoparticle surface. Methionine-capped Ag and Au nanoparticles (NPs) were tested as inhibitors of AChE, and they showed moderate inhibitory potential toward AChE. NPs are much larger than enzyme molecules and cannot enter the active site gorge, so inhibition occurs by blockage of the enzyme's active site due to the adsorption of AChE on the surface of the NPs. Ag and Au methionine-capped NPs have the potential to be further investigated for use in the treatment of cognitive impairment accompanying depression and Alzheimer's disease. We want to thank Prof. Igor Pašti for the graphic design. More information can be found in the Research Article by B. B. Laban and co-workers.

Periosteum-inspired in situ CaP generated nanocomposite hydrogels with strong bone adhesion and superior stretchability for accelerated distraction osteogenesis

BackgroundDistraction osteogenesis (DO) is an efficacious but lengthy procedure to reconstruct segmental bone defects under the principle of tension-stress, during which the periosteum-mediated mechanical stimulation plays a pivotal role. Inspired by the dynamic process of DO and the mechanical stimulation of periosteum, a new design of bionic periosteum was developed to simulate the mechanical transduction of natural periosteum for the application in DO procedure.MethodsIn this study, an injectable organic-inorganic hybrid hydrogel was developed based on a novel combination of the PEGylated poly (glycerol sebacate) (PEGS) polymer network and in situ formed CaP nanoparticles (ICPNs). Rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cultured and tested in vitro to evaluate biocompatibility, cell adhesion, proliferation, and pro-osteogenic and pro-angiogenic activity. In vivo experiments were conducted in the rat tibial model of distraction osteogenesis.ResultsThe developed nanocomposite hydrogels exhibited excellent injectability, robust bone adhesion, superior stretchability, and enhanced osteogenic activity. The results of in vitro and in vivo studies showed that PEGS/ICPN hydrogels could promote new bone formation and mineralization during the dynamic distraction process through the synergistic effects of angiogenesis and osteogenesis.ConclusionsThis periosteum-inspired nanocomposite hydrogel represents a mechanobiology approach for effectively restoring large bone defects through the dynamic DO process.

In vitro and in vivo osteogenesis up-regulated by two-dimensional nanosheets through a macrophage-mediated pathway.

Two-dimensional (2D) nanomaterials are attracting more and more interest in regenerative medicine due to their unique properties; however 2D biomimetic calcium mineral has not yet been developed and demonstrated application for bone tissue engineering. Here we described a novel calcium phosphate material with a 2D nanostructure that was synthesized using collagen and sodium alginate as the template. In vitro performance of the nanocrystalline material was evaluated, and we found that 2D CaP nanoparticles (NPs) enhanced the in vitro osteogenic differentiation of rat mesenchymal stem cells (rMSCs) through a macrophage-mediated signal pathway, when co-cultured with RAW 264.7 cells, rather than direct NP/stem cell interaction. A 2D topology structured surface was constructed by encapsulating the CaP nanomaterials in a gelatin hydrogel, which was demonstrated to be able to mediate in vivo ossification through a macrophage polarization related pathway in a femur defect rat model, and allowed the optimal therapeutic outcome compared to normal CaP counterparts. Our current work may have enlightened a new mechanism regarding NP-induced stem cell differentiation through immunoregulation, and the 2D CaP encapsulated hydrogel scaffold may serve as a potential alternative to autograft bone for orthopedic applications.

Enhanced removal of zinc and cadmium from water using carboxymethyl cellulose-bridged chlorapatite nanoparticles

Zinc (Zn2+) and cadmium (Cd2+) in water pose serious threats to human health and the environment. In search for a more effective treatment technology, we prepared a type of carboxymethyl cellulose (CMC) bridged chlorapatite (CMC-CAP) nanoparticles and tested the material for removal of Zn2+ and Cd2+ from water. CMC macromolecules were attached to CAP by bidentate bridging and hydrogen bonding, preserving the high adsorption capacity of CAP nanoparticles while allowing for easy gravity-separation of the nanoparticles. CMC-CAP showed rapid adsorption kinetics and 22.8% and 11.2% higher equilibrium uptake for Zn2+ and Cd2+, respectively, than pristine CAP. An extended dual-mode isotherm model, which takes into account both sorption and chemical precipitation, provided the best fits to the sorption isotherms, giving a maximum Langmuir sorption capacity of 141.1 mg g−1 for Zn2+ and 150.2 mg g−1 for Cd2+ by CMC-CAP. Na+ at up to 5 mM showed modest effects on the uptake of the heavy metals, while 2–5 mM of Ca2+ exerted notable inhibitive effects. Dissolved organic matter (up to 5 mg L−1 as TOC) inhibited the Zn2+ uptake by 16.5% but enhanced the Cd2+ removal by 8.6%. Material characterizations and surface binding analyses revealed that ion exchange, surface precipitation, and surface complexation were the removal mechanisms for the heavy metals. This study demonstrates stabilizer bridging may serve as a convenient strategy to facilitate water treatment uses of nanoparticles.

Biocomposite based on nanoscale calcium phosphate and collagen from Nile tilapia (Oreochromis niloticus) skin: Properties and morphological features

This work proposes the synthesis of biocomposites with nanoscale calcium phosphate (nCaP) and collagen (extracted from fish skin), aiming at a possible application as artificial bone graft. Biocomposite micrographs show needle-shaped and aggregated CaP nanoparticles, with undefined orientation on the surface of the collagen matrix. In addition, the obtained nCaP-Collagen biocomposite had a composition of 6.5% water, 53.9% collagen and 39.6% nCaP, exhibiting similar characteristics to natural bones in mineralization stage, such as: calcium (Ca) / potassium (P) ratio of 1.54, featuring a non-stoichiometric hydroxyapatite (Ca/P < 1.67, which corresponds to biological hydroxyapatite); low crystallinity (ICr = 0.34); and elasticity modulus (32.1 ± 4.0 MPa) close to the internal compartment of human bone. Thus, the nCaP-Collagen has suitable physical and morphological characteristics for potential application as artificial bone graft.

Enhanced Anti-Bacterial Activity Of Biogenic Silver Nanoparticles Synthesized From Terminalia mantaly Extracts.

BackgroundThe global increase in outbreaks and mortality rates associated with multi-drug-resistant (MDR) bacteria is a major health concern and calls for alternative treatments. Natural-derived products have shown potential in combating the most dreadful diseases, and therefore serve as an effective source of bioactive compounds that can be used as anti-bacterial agents. These compounds are able to reduce metal ions and cap nanoparticles to form biogenic nanoparticles (NPs) with remarkable anti-bacterial activities. This study explores the use of Terminalia mantaly (TM) extracts for the synthesis of biogenic silver NPs (TM-AgNPs) and the evaluation of their antibacterial activity.MethodsTM-AgNPs were synthetized by the reduction of AgNO3 with aqueous and methanolic TM extracts. UV–visible (UV-vis) spectrophotometry, Dynamic Light Scattering (DLS), Transmission Electron Microscopy, and Fourier Transform Infrared (FTIR) analyses were used to characterise the TM-AgNPs. Anti-bacterial activity of the TM extracts and TM-AgNPs was evaluated against eight bacterial strains using the broth microdilution assay. The growth inhibitory kinetics of the bio-active TM-AgNPs was assessed on susceptible strains for a period of 8 hrs.ResultsPolycrystalline biogenic AgNPs with anisotropic shapes and diameter range of 11 to 83 nm were synthesized from the TM extracts. The biogenic TM-AgNPs showed significant antibacterial activity compared to their respective extracts. The MIC values for TM-AgNPs and extracts were 3 and 125 µg/mL, respectively. Biogenic AgNPs synthesised from the aqueous TM leaf extract at 25°C (aTML-AgNPs-25°C) showed significant antibacterial activity against all the bacterial strains tested in this study. Their bactericidal effect was particularly higher against the Streptococcus pneumoniae and Haemophilus influenzae.ConclusionThis study demonstrated the ability of TM extracts to synthesize biogenic AgNPs. The NPs synthesized from the aqueous TM extracts demonstrated higher antibacterial activity against the tested microorganisms compared to the methanolic extracts. Studies are underway to identify the phytochemicals involved in NP synthesis and their mechanism of action.

Chondroitin Sulphate Decorated Polymeric Nanoparticles: An Effective Carrier for Enhancement of Lung Cancer Targeting Capabilities of Anticancer Drug

Background: Currently, cancer is rising as one of the dominant causes of human deaths worldwide. The application of nano-carriers may help to treat cancer through the delivery of anticancer drugs inside the tumor cells. Objective: The foremost objective behind this research was to formulate chondroitin sulfate tailored cellulose acetate phthalate (CSAC) core shield nanoparticles (NPs) containing 5-Fluorouracil (5-FU) as an anticancer drug. Methods: The FTIR and 1H-NMR spectroscopic methods were used to analyze and characterize the formulation of CSAC copolymer. NPs were typified by Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), Atomic Force Microscopy (AFM), Entrapment efficiency and in-vitro drug release. Results: CSAC NPs were found to exhibit moderate release (95.59±0.15% in 34hrs) than CAP NPs (78.97±0.08% in 8 hours). In the course of cytotoxicity examination in A549 cancer cell line, the results revealed that these 5-FU loaded CSAC NPs showed an immense cytotoxic potentiality. Moreover, CSAC NPs exhibit least hemolytic activity when compared with CAP NPs and plain 5-FU. Conclusion: Conclusively, it was found that the CSAC NPs is an efficient carrier system for the better release of 5-FU in lung cancer.

Influenza A(H5N1) Virus Subunit Vaccine Administered with CaPNP Adjuvant Induce High Virus Neutralization Antibody Titers in Mice.

The highly pathogenic avian influenza H5N1 virus continues to spread globally in domestic poultry with sporadic transmission to humans. The possibility for its rapid transmission to humans raised global fears for the virus to gain capacity for human-to-human transmission to start a future pandemic. Through direct contact with infected poultry, it caused the largest number of reported cases of severe disease and death in humans of any avian influenza strains. For pandemic preparedness, use of safe and effective vaccine adjuvants and delivery systems to improve vaccine efficacy are considered imperative. We previously demonstrated CaPtivate's proprietary CaP nanoparticles (CaPNP) as a potent vaccine adjuvant/delivery system with ability to induce both humoral and cell-mediated immune responses against many viral or bacterial infections. In this study, we investigated the delivery of insect cell culture-derived recombinant hemagglutinin protein (HA) of A/H5N1/Vietnam/1203/2004 virus using CaPNP. We evaluated the vaccine immunogenicity in mice following two intramuscular doses of 3μg antigen combined with escalating doses of CaPNP. Our data showed CaPNP-adjuvanted HA(H5N1) vaccines eliciting significantly higher IgG, hemagglutination inhibition, and virus neutralization titers compared to non-adjuvanted vaccine. Among the four adjuvant doses that were tested, CaPNP at 0.24% final concentration elicited the highest IgG and neutralizing antibody titers. We also evaluated the inflammatory response to CaPNP following a single intramuscular injection in guinea pigs and showed that CaPNP does not induce any systemic reaction or adverse effects. Current data further support our earlier studies demonstrating CaPNP as a safe and an effective adjuvant for influenza vaccines.

DNA-Templated Strontium-Doped Calcium Phosphate Nanoparticles for Gene Delivery in Bone Cells.

Calcium phosphates (CaPs), constituents of the inorganic phase of natural bone, are highly biocompatible and biodegradable. Strontium (Sr) regulates the formation and resorption of bone. Incorporation of Sr into CaPs may target genes of interest to bone cells while regulating their function. In this work, we developed a single-step synthesis method to prepare Sr-doped CaP nanoparticles (SrCaP-DNA NPs) by using DNA as a template for controlling the mineralization and the stability of the colloidal solution. The resulting nanoparticles were monodispersed with well-controlled size, morphology, and composition. By using this method, we were able to fabricate CaP NPs with varying contents of Sr2+. We demonstrated that the stability of CaP NPs in extracellular environments increased when Sr2+ partially replaced Ca2+ in CaP NPs. We showed that the cellular uptake of SrCaP-DNA NPs and the efficiency of gene transfer and alkaline phosphatase activity in human fetal osteoblastic cell line (hFOB1.19) were dependent on the content of Sr2+ in NPs. Together with other studies, our results suggest SrCaP-DNA NPs can be optimized for targeted gene transfer to regulate function of bone cells, enabling applications such as bone tissue engineering and treating bone diseases.

Synthesization and characterization of chlorhexidine/calcium phosphate/poly(lactic-co-glycolic acid) bone cement

Calcium (Ca) and phosphorus (P) elements are important for bone growth and bone remodeling process while chlorhexidine (CHX) is mainly used as an antiseptic due to its broad antibacterial effects. In this study, CaP nanoparticles were synthesized by a wet chemical route from the precursors of calcium hydroxide (CaOH) and diammonium hydrogen phosphate, (NH4)2HPO4. Poly(lactic-co-glycolic acid) PLGA polymer was incorporated into the mixture of CaP, acted as a matrix binder to form bone cement composite. Different concentrations of CHX (0.5, 1.0, 1.5 and 2.0 mM) were then added into the CaP/PLGA mixtures (CHX/CaP/PLGA bone cements). The bone cements were then characterized by ATR-FTIR, XRD and SEM analyses. The CHX was successfully incorporated into the bone cements, indicated by the appearance of aromatic amine and alkane C–H stretching vibrations which contributed by the ring and long hydrocarbon chain of CHX. The XRD spectra of bone cements showed poorly crystalline phase of apatite. A porous structure of bone cements was also observed with the dispersion of CaP nanoparticles over the PLGA. The CHX/CaP/PLGA bone cement is intended for bone resorption and bone infection applications that require further exploration on its capability to act as bone cement.

Flame-synthesized nickel-silver nanoparticle inks provide high conductivity without sintering

A new concept for the synthesis of conductive metal nanoparticle inks (nano-inks) is introduced using a one-step continuous flame-based process. Bimetallic nickel (Ni)-silver (Ag) nanopowders are simultaneously produced and functionalized in a High Temperature Reducing Jet (HTRJ) reactor. The HTRJ process allows rapid aerosol (gas phase) formation of multicomponent metal nanoparticles with relatively high production rates from low-cost metal precursors. Octylamine, a volatile aliphatic amine, is sprayed into the reactor effluent after the particle formation zone to cap nanoparticles as they form. Ni-Ag Functionalized Nano Powders (FNPs) were characterized and compared with Bare Nano Powders (BNPs) to verify that in situ ligand attachment was successful. Nano-inks were prepared by dispersing FNPs in an organic solvent. Conductive films were fabricated using different nano-ink compositions starting from pure Ni to 50 wt% Ni. With the use of a small capping agent, films containing 50 wt% (65 at%) Ni provide an electrical conductivity of 5.14 × 104 S m−1 without any post-processing. Conductivity increased to 4.22 × 105 S m−1 after thermal annealing in an inert environment. These sintering-free bimetallic conductive nanoparticles can be used as a lower cost replacement for current silver inks for single-step printing of conductive traces without post-processing.

Self-Assembled Injectable Nanocomposite Hydrogels Coordinated by in Situ Generated CaP Nanoparticles for Bone Regeneration.

Due to the great similarity to the natural extracellular matrix and minimally invasive surgeries, injectable hydrogels are appealing biomaterials in cartilage and bone tissue engineering. Nevertheless, undesirable mechanical properties and bioactivity greatly hamper their availability in clinic applications. Here, we developed an injectable nanocomposite hydrogel by in situ growth of CaP nanoparticles (ICPNs) during the free-radical polymerization of dimethylaminoethyl methacrylate (DMAEMA) and 2-hydroxyethyl methacrylate (HEMA) matrix (PDH) for bone regeneration. The ICPNs are self-assembled by incorporation of poly-l-glutamic acid (PGA) with abundant carboxyl functional groups during the formation of carboxyl-Ca2+ coordination and further CaP precipitation. Furthermore, the carboxyl groups of PGA could interact with the tertiary amines of DMAEMA fragments and thus improve the mechanical strength of hydrogels. Upon mixing solutions of DMAEMA and HEMA bearing PGA, Ca2+, and PO43-, this effective and dynamic coordination led to the rapid self-assembly of CaP NPs and PDH nanocomposite hydrogels (PDH/mICPN). The obtained optimal nanocomposite hydrogels exhibited suitable injectable time, an enhanced tensile strength of 321.1 kPa, and a fracture energy of 29.0 kJ/m2 and dramatically facilitated cell adhesion and upregulated osteodifferentiation compared to hydrogels prepared by blending ex situ prefabricated CaP NPs. In vivo experiments confirmed the promoted osteogenesis, which shows a striking contrast to pure PDH hydrogels. Additionally, the methacrylate groups on the monomers could easily be functionalized with aptamers and thereby facilitate recognition and capturing of bone marrow stromal cells both in vitro and in vivo and strengthen the bone regeneration. We believe that our conducted research about in situ self-assembled CaP nanoparticle-coordinated hydrogels will open a new avenue for bone regeneration in the future endeavors.

A synergistic approach for management of lung carcinoma through folic acid functionalized co-therapy of capsaicin and gefitinib nanoparticles: Enhanced apoptosis and metalloproteinase-9 down-regulation

BackgroundLung cancer is one of the most lethal cancers and lacks effective treatment strategy. Therapeutic efficacy can be improved through active targeting approach utilizing surface engineered nanoparticles (NPs) for cancer therapy. PurposeThe present study envisioned development of Folic acid (FA) functionalized NPs for co-administration of gefitinib (Gnb) and capsaicin (Cap) respectively to enhance the therapeutic outcome by disabling the barriers related to tumors extracellular matrix. Research methods and procedureThe FA conjugated Gnb/Cap polymeric (PLGA-PEG) NPs were prepared using oil in water emulsion technique and methodically developed using Quality by Design (QbD) concept employing central composite design. The developed formulations were subjected to various in vitro (A549 cell lines) and in vivo evaluations in urethane-induced lung cancer. ResultsThe modified NPs displayed particle sizes of 217.0 ± 3.2 nm and 213.0 ± 5.2 nm and drug release of 85.65 ± 3.21% and 81.43 ± 4.32% for Gnb and Cap respectively. Higher cellular uptake and lower cell viability in A549 cell line was displayed by functionalized NPs compared to free drug. Co administration of Gnb and Cap NPs displayed significant targeting potential, reduction in tumor volume while restoring the biochemical parameters viz., SOD, catalase, TBARS and protein carbonyl, towards normal levels when compared with toxic group. Significant down regulation was observed for anti-apoptotic proteins (MMP-9) and up regulation of pro-apoptotic proteins (caspase-3, caspase-9 and MMP-9) with co-therapy of Gnb and Cap NPs, when compared with individual therapy through Gnb/Cap. ConclusionPotentiation of the action of Gnb when co administered with Cap NPs can be a promising breakthrough for developing safe, effective and targeted delivery for lung carcinoma therapy.

Eudragit encapsulated cationic poly (lactic-co-glycolic acid) nanoparticles in targeted delivery of capecitabine for augmented colon carcinoma therapy

The present study was aimed at developing capecitabine loaded poly(lactic-co-glycolic acid) (PLGA Cap) based nanoparticles (NPs) formulation as a biodegradable polymeric drug carrier to treat colon cancer. NPs were prepared by the double emulsion solvent evaporation technique, then surface modified using chitosan and encapsulated in Eudragit® S100. Full factorial design (FFD) matrix was used to study the influence of three different independent variables on the responses particle size, Zeta potential, and encapsulation efficiency. For that, a three-level factorial design experiment was used for obtaining a mathematical model and prediction of the optimized formulation. The optimized PLGA Cap NPs were analyzed using DSC, AFM and Raman chemical spectral mapping. The particle size was found to be 386.13 ± 54.18 nm with polydispersity index 0.28 and Zeta potential of +12.3 ± 2.1 mV with an encapsulation efficiency of 63.81 ± 5.69%. In vitro drug release studies results showed a burst release followed by sustained release of Cap in the simulated colonic media with matrix-diffusion assisted drug release. The optimized NPs depicted higher in vitro mucoadhesion compared to the unmodified NPs. In vitro cell line studies showed that the PLGA Cap NPs exhibited significant anti-proliferative activity. The NPs were stable according to studies carried out following ICH Guidelines. All these outcomes signify the promising applicability of the formulated PLGA Cap NPs as a novel and targeted drug delivery system for colon carcinoma therapy with better patient compliance.

Semiconducting Photothermal Nanoagonist for Remote-Controlled Specific Cancer Therapy.

Nanomedicine have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively. Under multiple NIR laser irradiation at the time scale of seconds, the nanoagonists can repeatedly and locally release Cap to multiply activate TRPV1 channels on the cellular membrane; the cumulative effect is the overinflux of ions in mitochondria followed by the induction of cell apoptosis specifically for TRPV1-postive cancer cells. Multiple transient activation of TRPV1 channels is essential to induce such a cell death both in vitro and in vivo because both free Cap and simple Cap-encapsulated nanoparticles fail to do so. The photothermally triggered release also ensures a high local concentration of the TRPV1 agonist at tumor site, permitting specific cancer cell therapy at a low systemic administration dosage. Our study thus demonstrates the first example of ion-channel-specific and remote-controlled drug-delivery system for cancer cell therapy.

Preparation of dexamethasone-loaded biphasic calcium phosphate nanoparticles/collagen porous composite scaffolds for bone tissue engineering.

Scaffolds play a crucial role for regeneration of large bone defects. Biomimetic scaffolds having the same composition of natural bone and a controlled release of osteoinductive factors are desirable for promotion of bone regeneration. In this study, composite scaffolds of collagen and biphasic CaP nanoparticles (BCP NPs) with a controlled release nature of dexamethasone (DEX) were prepared and their porous structures were controlled by using ice particulates. In vitro cell culture and in vivo implantation experiments demonstrated the composite scaffolds exerted synergistic effects on the osteogenic differentiation of hMSCs and bone regeneration. The composite scaffolds also showed promotive effect on the formation of capillary blood vessels in the regenerated bone. This study is the first research to prepare DEX-loaded BCP NPs/collagen porous composite scaffolds. The superior performance of the composite scaffolds indicates the composite scaffolds should be useful for bone tissue engineering.

Facile one-pot fabrication of calcium phosphate-based composite nanoparticles as delivery and MRI contrast agents for macrophages

We developed a facile one-pot fabrication process for magnetic iron oxide–calcium phosphate (IO–CaP) composite nanoparticles via coprecipitation in labile supersaturated CaP solutions containing IO nanocrystals. All the source solutions used were clinically approved for injection, including water and magnetic IO nanocrystals (ferucarbotran, used as a negative magnetic resonance imaging (MRI) contrast agent). This ensured that the resulting nanoparticles were pathogen- and endotoxin-free. The dispersants used were clinically approved heparin sodium (heparin) or adenosine triphosphate disodium hydrate (ATP), which were added to the IO-containing labile supersaturated CaP solutions. Both heparin and ATP coprecipitated with CaP and ferucarbotran to form heparin- and ATP-modified IO–CaP nanoparticles, respectively, with a hydrodynamic diameter of a few hundred nanometers. Both the resulting nanoparticles exhibited relatively large negative zeta potentials, caused by the negatively charged functional groups in heparin and ATP, which improved the particle dispersibility when compared to non-modified IO–CaP nanoparticles. The heparin-modified IO–CaP nanoparticles were effectively ingested by murine macrophages (RAW264.7) without showing significant cytotoxicity but barely ingested by non-phagocytotic human umbilical vein endothelial cells, indicating the potential of these nanoparticles for targeted delivery to macrophages. The heparin-modified IO–CaP nanoparticles exhibited a negative contrast enhancing ability for MRI. Our results show that IO–CaP nanoparticles have potential as delivery and MRI contrast agents for macrophages.