Calcium Phosphate-Coated Lipid Nanoparticles as a Potential Tool in Bone Diseases Therapy (original) (raw)
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Pharmaceutics
Osteosarcoma (OSA) is the most frequently diagnosed primary malignant bone tumor in humans and dogs. In both species, standard chemotherapy can be limited by multidrug resistance of neoplastic cells, which prevents intracellular accumulation of cytotoxic drugs, resulting in chemotherapy failure. In this study, a lipophilic ester of doxorubicin (C12DOXO) was loaded into nanoparticles (NPs) using the “cold microemulsion dilution” method. The resulting NPs were then coated with calcium phosphate (CaP) in two different ways to have calcium or phosphate ions externally exposed on the surface. These systems were characterized by determining mean diameter, zeta potential, and drug entrapment efficiency; afterward, they were tested on human and canine OSA cells to study the role that the coating might play in increasing both drug uptake into tumor cells and cytotoxicity. Mean diameter of the developed NPs was in the 200–300 nm range, zeta potential depended on the coating type, and C12DOXO ...
Calcium phosphate-based composite nanoparticles in bioimaging and therapeutic delivery applications
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2011
Bioimaging and therapeutic delivery applications are areas of biomedicine where nanoparticles have had significant impact, but the use of a nanomaterial in these applications can be limited by its physicochemical properties. Calcium phosphate-based composite nanoparticles are nontoxic and biodegradable, and are therefore considered attractive candidates for bioimaging and therapeutic drug delivery applications. Also, the pH-dependent solubility profiles of calcium phosphate materials make this class of nanoparticles especially useful for in vitro and in vivo delivery of dyes, oligonucleotides, and drugs. In this article, we discuss how calcium phosphate-based composite nanoparticles fulfill some of the requirements typically made for nanoparticles in biomedical applications. We also highlight recent studies in bioimaging and therapeutic delivery applications focusing on how these studies have addressed some of the challenges associated with using these nanoparticles in bioimaging and delivery of therapeutics.
Nanomedicine, 2016
During the last two decades although many calcium phosphate based nanomaterials have been proposed for both drug delivery, and bone regeneration, their coating applications have been somehow slow due to the problems related to their complicated synthesis methods. In order to control the efficiency of local drug delivery of a biomaterial the critical pore sizes as well as good control of the chemical composition is pertinent. A variety of calcium phosphate based nanocoated composite drug delivery systems are currently being investigated. This review aims to give an update into the advancements of calcium phosphate nanocoatings and thin film nanolaminates. In particular recent research on PLA/hydroxyapatite composite thin films and coatings into the slow drug delivery for the possible treatment of osteomyelitis is covered.
Coatings, 2020
The high incidence of bone defect cases necessitates a rapid development of cost-effective bone tissue engineering approaches. Bone growth factors such as bone morphogenetic protein-2 (BMP-2) play a vital role in bone tissue engineering. The osteoinductive efficacy of BMP-2 and other osteogenic growth factors is highly dependent on their dose and delivery mode. Slow and sustained delivery of a low dose of BMP-2 promotes bone defect healing. However, the burst release of a high dose of BMP-2 not only fails to promote bone healing but also causes adverse local and systemic effects. The biomimetic calcium phosphate (BioCaP) coating technique guarantees a slow, gradual, and local release of BMP-2 to mimic its natural release from the bone matrix under physiological conditions. Therefore, BioCaP coatings have long been regarded as a promising drug carrier for growth factors. In this mini-review, we give a brief introduction to BioCaP coatings regarding their preparation techniques, physi...
Nano Letters, 2008
Paradigm-shifting modalities to more efficiently deliver drugs to cancerous lesions require the following attributes: nanoscale-size, targetability and stability under physiological conditions. Often, these nanoscale drug delivery vehicles are limited due to agglomeration, poor solubility or cytotoxicity. Thus, we have designed a methodology to encapsulate hydrophobic antineoplastic chemotherapeutics within a 20-30 nm diameter, pH-responsive, non-agglomerating, non-toxic calcium phosphate nanoparticle matrix. In the present study, we report on calcium phosphate nanocomposite particles (CPNP) that encapsulate both fluorophores and chemotherapeutics, are colloidally stable in physiological solution for extended time at 37°C and can efficaciously deliver hydrophobic antineoplastic agents, such as ceramide, in several cell model systems. Keywords Calcium phosphate; nanoparticles; ceramide; in vitro chemotherapy; cancer Nanoparticles with fluorescent properties have been prepared by several synthetic approaches, 1-7 some of which exploit the benefits of self-assembly, particularly reverse micelles, to prepare a wide range of nanocolloids. 8-18 For example, reverse micelle techniques have been used to produce nearly monodisperse fluorescent semiconductor quantum dots with various shapes and sizes as well as to capture organic fluorophores within silica inorganic matrices. 2-6, 19, 20 While suitable for drug delivery in vitro where immune responses do not exist, semiconductor or silica nanocomposite particles with surface decoration are not particularly efficacious for drug delivery in humans. 1, 6, 21 Biodegradation of the decorated therapeutics prior to delivery can be severe. To overcome these limitations and realize the full potential of nanocomposite drug and fluorophore delivery systems, we have developed non-agglomerating nano-sized calcium phosphatebased composite particles. Reasonably high, but benign, concentrations of calcium and phosphate (1 to 5mM) occur in all vertebrates and are naturally non-toxic as well as bioresorbable. 22-24 Calcium phosphate has been widely used to provide transfection of DNA and deliver drugs via surface decoration of calcium phosphate microparticles. 2, 5, 13, 14, 16, 25 The present study reports the colloidal properties of stable, non-aggregating, 20 nm nanocomposite calcium phosphate particles embedded with fluoroprobes and a small
Calcium Phosphate Nanoparticles for Therapeutic Applications in Bone Regeneration
Nanomaterials, 2019
Bone injuries and diseases constitute a burden both socially and economically, as the consequences of a lack of effective treatments affect both the patients' quality of life and the costs on the health systems. This impended need has led the research community's efforts to establish efficacious bone tissue engineering solutions. There has been a recent focus on the use of biomaterial-based nanoparticles for the delivery of therapeutic factors. Among the biomaterials being considered to date, calcium phosphates have emerged as one of the most promising materials for bone repair applications due to their osteoconductivity, osteoinductivity and their ability to be resorbed in the body. Calcium phosphate nanoparticles have received particular attention as non-viral vectors for gene therapy, as factors such as plasmid DNAs, microRNAs (miRNA) and silencing RNA (siRNAs) can be easily incorporated on their surface. Calcium phosphate nanoparticles loaded with therapeutic factors have also been delivered to the site of bone injury using scaffolds and hydrogels. This review provides an extensive overview of the current state-of-the-art relating to the design and synthesis of calcium phosphate nanoparticles as carriers for therapeutic factors, the mechanisms of therapeutic factors' loading and release, and their application in bone tissue engineering.
Lipid Nanoparticles and Liposomes for Bone Diseases Treatment
Biomedicines
Because of their outstanding biocompatibility, sufficient capacity to control drug release, and passive targeting capability, lipid nanoparticles are one of the world’s most widely utilized drug delivery systems. However, numerous disadvantages limit the use of lipid nanoparticles in clinical settings, especially in bone regeneration, such as challenges in transporting, storing, and maintaining drug concentration in the local area. Scaffolds are frequently employed as implants to provide mechanical support to the damaged area or as diagnostic and imaging tools. On the other hand, unmodified scaffolds have limited powers in fostering tissue regeneration and curing illnesses. Liposomes offer a solid foundation for the long-term development of various commercial solutions for the effective drug delivery-assisted treatment of medical conditions. As drug delivery vehicles in medicine, adjuvants in vaccination, signal enhancers/carriers in medical diagnostics and analytical biochemistry, ...