Synthesis of hydroxyapatite for biomedical applications

Patients treated with conventional cancer chemotherapy suffer from side effects of the drugs due to non-selective action of chemotherapeutic drugs to normal cells. Active targeting nanoparticles that are conjugated to targeting ligands on the surface of nanoparticles play an important role in improving drug selectivity to the cancer cell. Several chemotherapeutic drugs and traditional/herbal medicines reported for anticancer activities have been investigated for their selective delivery to cancer cells by active targeting nanoparticles. This systematic review summarizes reports on this application. Literature search was conducted through PubMed database search up to March 2017 using the terms nanoparticle, chemotherapy, traditional medicine, herbal medicine, natural medicine, natural compound, cancer treatment, and active targeting. Out of 695 published articles, 61 articles were included in the analysis based on the predefined inclusion and exclusion criteria. The targeting ligands included proteins/peptides, hyaluronic acid, folic acid, antibodies/antibody fragments, aptamer, and carbohydrates/polysaccharides. In vitro and in vivo studies suggest that active targeting nanoparticles increase selectivity in cellular uptake and/or cytotoxicity over the conventional chemotherapeutic drugs and non-targeted nanoparticle platform, particularly enhancement of drug efficacy and safety. However, clinical studies are required to confirm these findings.

/pdf/application-of-active-targeting-nanoparticle-delivery-system-1idyav39pw.pdf

Application of active targeting nanoparticle delivery system for chemotherapeutic drugs and traditional/herbal medicines in cancer therapy: a systematic review.

Quercetin (Que) and its derivatives are naturally occurring phytochemicals with promising bioactive effects. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer's, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, as well as its anticancer activity against different cancer cell lines has been recently reported. Que and its derivatives are found predominantly in the Western diet, and people might benefit from their protective effect just by taking them via diets or as a food supplement. Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que nanoparticles appear as a promising platform to enhance their bioavailability. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of Que.

Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health.

Calcium-based (CaXs) biomaterials including calcium phosphates, calcium carbonates, calcium silicate and calcium fluoride have been widely utilized in the biomedical field owing to their excellent biocompatibility and biodegradability. In recent years, CaXs biomaterials have been strategically integrated with imaging contrast agents and therapeutic agents for various molecular imaging modalities including fluorescence imaging, magnetic resonance imaging, ultrasound imaging or multimodal imaging, as well as for various therapeutic approaches including chemotherapy, gene therapy, hyperthermia therapy, photodynamic therapy, radiation therapy, or combination therapy, even imaging-guided therapy. Compared with other inorganic biomaterials such as silica-, carbon-, and gold-based biomaterials, CaXs biomaterials can dissolve into nontoxic ions and participate in the normal metabolism of organisms. Thus, they offer safer clinical solutions for disease theranostics. This review focuses on the state-of-the-art progress in CaXs biomaterials, which covers from their categories, characteristics and preparation methods to their bioapplications including diagnosis, treatment, and theranostics. Moreover, the current trends and key problems as well as the future prospects and challenges of CaXs biomaterials are also discussed at the end.

Calcium-based biomaterials for diagnosis, treatment, and theranostics

Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application.

Mitochondria and nuclei dual-targeted heterogeneous hydroxyapatite nanoparticles for enhancing therapeutic efficacy of doxorubicin

A targeted nanoplatform co-delivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer.

The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by 1H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspension in the duodenum and jejunum segments (p <  0.01), which was comparable to verapamil coperfusion effect. Similarly, CsA + CNC mixture and CsA-CNC/LHR MPMs significantly increased the oral bioavailability of CsA as compared to CsA suspension. These results suggest that CNC conjugate might be considered as a promising gastrointestinal absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.

https://www.tandfonline.com/doi/pdf/10.1080/10717544.2016.1189625

Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs

Drug efflux induced by multidrug resistance (MDR) overexpression, as well as secondary drug resistance caused by subtoxic drug microenvironments as a result of inefficient drug release of nanoscopic drug carriers in tumor cells, are major bottlenecks for chemotherapy. In order to overcome these limitations, we have devised a synergism-based polymer supramolecular nanoassembly (LH) by combining hyaluronic acid (HA) modified curcumin (HA-CUR) with a pH-sensitive low molecular weight heparin (LMWH) derivative modified doxorubicin (L-DOX). Our study proved that HA modification not only facilitated tumor targeting drug delivery efficiency through CD44 receptors-mediated active tumor-targeting strategy but also significantly enhanced the MDR reversion effect of CUR by improving its biological stability in different physiological environments. Also, the L-DOX in LH could trigger rapid and effective DOX release under a varied pH value environment, thereby overcoming secondary drug resistance. More importantly, a synergistic antitumor effect was achieved by optimizing the ratio of HA-CUR and L-DOX in LH. Furthermore, LH showed a superior therapeutic effect over free DOX in two mouse models of human cancer. Taken together, these results demonstrated that LH might serve as an efficient platform for delivery of therapeutic payloads to overcome MDR.

Intracellular self-disassemble polysaccharide nanoassembly for multi-factors tumor drug resistance modulation of doxorubicin.

The invention relates to a curcumin-polysaccharide conjugate as well as a preparation method and application thereof. The preparation method comprises the following steps of: grafting amino acid at one terminal of a diamine compound to polysaccharide through amidation to obtain a polysaccharide macromolecule with a free terminal of amino acid; and introducing curcumin on the polysaccharide frame by a Schiff base reaction. The preparation method is characterized in that 1, the water solubility and in-vivo and in-vitro stability of the curcumin can be improved due to grafting modification on the curcumin, and the generated curcumin-polysaccharide conjugate can be used as a novel macromolecular medicament indepterminalently; 2, the curcumin-polysaccharide conjugate has a strong oral absorption promoting effect, is high in safety, and can achieve the effects of promoting medicament absorption, improving the curative effect, reducing the toxic and side effect of the conjugate and the like; and 3, the amphipathy of the polysaccharide molecule is improved by introducing the hydrophobic group curcumin, so that the curcumin-polysaccharide conjugate can be self-assembled into nano-micelle, and can be used as a vector of an insoluble medicament. The preparation method is simple, low in cost, and applicable to large-scale continuous production.

Jiang Ni

Papers

Mitochondria and nuclei dual-targeted heterogeneous hydroxyapatite nanoparticles for enhancing therapeutic efficacy of doxorubicin

A targeted nanoplatform co-delivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer.

Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs

Intracellular self-disassemble polysaccharide nanoassembly for multi-factors tumor drug resistance modulation of doxorubicin.

Curcumin-polysaccharide conjugate as well as preparation method and application thereof