Nanocarrier Drug Delivery Systems Research Articles

The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-block-poly(d,l-lactic acid) in rat

Monomethoxy poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-PLA) is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier (nanocarrier) in drug delivery. Understanding the in vivo fate of PEG-PLA is required to evaluate its overall safety and promote the development of PEG-PLA-based nanocarrier drug delivery systems. However, acquiring such understanding is limited by the lack of a suitable analytical method for the bioassay of PEG-PLA. In this study, the pharmacokinetics, biodistribution, metabolism and excretion of PEG-PLA were investigated in rat after intravenous administration. The results show that unchanged PEG-PLA is mainly distributed to spleen, liver, and kidney before being eliminated in urine over 48 h mainly (>80%) in the form of its PEG metabolite. Our study provides a clear and comprehensive picture of the in vivo fate of PEG-PLA which we anticipate will facilitate the scientific design and safety evaluation of PEG-PLA-based nanocarrier drug delivery systems and thereby enhance their clinical development.

Advanced Technologies in DNA-based Nanomedicine

: The application of nanotechnology in medicine and pharmaceutical purpose suggested a novel procedure in the nanotechnology terminology as nanomedicine. There is a wide range of applications for nanotechnology in medicine, such as the use of nanocarriers in drug delivery systems. Recently a remarkable attention to DNA has been made through its amazing functionality and its nature as a nanomaterial in biological systems. Since DNA is a biocompatible, the use of DNA as a nanomaterial in medicine has shown a great perspective of rational engineering of DNA nanostructures. According to new approaches in treatment of diseases in gene levels, gene therapy, using DNA as a nanomedicine possesses an important role in the medical sciences as the researchers published enormous papers and patents in the fields, for instance, the applications of DNA and DNA-based nanostructures as drug or gene nanocarriers, DNA-based diagnostics and DNA nanovasccines. Here, some examples of DNA-based nanomedicine in the patent frame were reviewed.

Complex Factors and Challenges that Affect the Pharmacology, Safety and Efficacy of Nanocarrier Drug Delivery Systems.

Major developments in nanomedicines, such as nanoparticles (NPs), nanosomes, and conjugates, have revolutionized drug delivery capabilities over the past four decades. Although nanocarrier agents provide numerous advantages (e.g., greater solubility and duration of systemic exposure) compared to their small-molecule counterparts, there is considerable inter-patient variability seen in the systemic disposition, tumor delivery and overall pharmacological effects (i.e., anti-tumor efficacy and unwanted toxicity) of NP agents. This review aims to provide a summary of fundamental factors that affect the disposition of NPs in the treatment of cancer and why they should be evaluated during preclinical and clinical development. Furthermore, this chapter will highlight some of the translational challenges associated with elements of NPs and how these issues can only be addressed by detailed and novel pharmacology studies.

Structural and mechanical characteristics of exosomes from osteosarcoma cells explored by 3D-atomic force microscopy.

Exosomes have recently gained interest as mediators of cell-to-cell communication and as potential biomarkers for cancer and other diseases. They also have potential as nanocarriers for drug delivery systems. Therefore, detailed structural, molecular, and biomechanical characterization of exosomes is of great importance for developing methods to detect and identify the changes associated with the presence of cancer and other diseases. Here, we employed three-dimensional atomic force microscopy (3D-AFM) to reveal the structural and nanomechanical properties of exosomes at high spatial resolution in physiologically relevant conditions. The substructural details of exosomes released from three different cell types were determined based on 3D-AFM force mapping. The resulting analysis revealed the presence of distinct local domains bulging out from the exosome surfaces, which were associated with the exosomal membrane proteins present on the outer surface. The nanomechanical properties of individual exosomes were determined from the 3D-force maps. We found a considerably high elastic modulus, ranging from 50 to 350 MPa, as compared to that obtained for synthetic liposomes. Moreover, malignancy-dependent changes in the exosome mechanical properties were revealed by comparing metastatic and nonmetastatic tumor cell-derived exosomes. We found a clear difference in their Young's modulus values, suggesting differences in their protein profiles and other exosomal contents. Exosomes derived from a highly aggressive and metastatic k-ras-activated human osteosarcoma (OS) cell line (143B) showed a higher Young's modulus than that derived from a nonaggressive and nonmetastatic k-ras-wildtype human OS cell line (HOS). The increased elastic modulus of the 143B cell-derived exosomes was ascribed to the presence of abundant specific proteins responsible for elastic fiber formation as determined by mass spectroscopy and confirmed by western blotting and ELISA. Therefore, we conclude that exosomes derived from metastatic tumor cells carry an exclusive protein content that differs from their nonmetastatic counterparts, and thus they exhibit different mechanical characteristics. Discrimination between metastatic and nonmetastatic malignant cell-derived exosomes would be of great importance for studying exosome biological functions and using them as diagnostic biomarkers for various tumor types. Our findings further suggest that metastatic tumor cells release exosomes that express increased levels of elastic fiber-associated proteins to preserve their softness.

Nanocarriers in the Enhancement of Therapeutic Efficacy of Natural Drugs

Abstract Since time immemorial, plant derived natural products have been used for the treatment of various human diseases before the intervention of modern medicine. The basis of modern medicine is still being inspired from traditional medicine and therapies. However, despite their tremendous therapeutic potential, these natural drugs often have poor bioavailability, metabolic instability, and aqueous insolubility. These factors greatly impede a natural drug’s commercialization potential as a mainstream medicine. Therefore, the development of nanocarrier drug delivery systems is indispensable in overcoming the various constraints of the bottlenecks which occur with natural drugs. Of particular interest in this review are four plant materials endogenous to China with the common names of barrenwort or horny goat weed (Epimedium), Shu Di Huang (Rehmannia glutinosa, RG), ginseng (Panax ginseng), and Dong Quai or female ginseng (Angelica sinensis, AS), each having been scientifically investigated for a wide range of therapeutic uses as has been originally discovered from the long history of traditional usage and anecdotal information by local population groups in Asia. The integration of natural drugs from the East and nanocarrier drug delivery systems developed from the West is paving the way towards further accurate and efficient medicine therapy. We further discuss the potential benefits of these plants and the enhancement of their therapeutic efficacy by nanotechnology intervention.

Perspectives of nano-carrier drug delivery systems to overcome cancer drug resistance in the clinics

Advanced cancer is still considered an incurable disease because of its metastatic spread to distal organs and progressive gain of chemoresistance. Even though considerable treatment progress and more effective therapies have been achieved over the past years, recurrence in the long-term and undesired side effects are still the main drawbacks of current clinical protocols. Moreover, a majority of chemotherapeutic drugs are highly hydrophobic and need to be diluted in organic solvents, which cause high toxicity, in order to reach effective therapeutic dose. These limitations of conventional cancer therapies prompted the use of nanomedicine, the medical application of nanotechnology, to provide more effective and safer cancer treatment. Potential of nanomedicines to overcome resistance, ameliorate solubility, improve pharmacological profile, and reduce adverse effects of chemotherapeutical drugs is thus highly regarded. Their use in the clinical setting has increased over the last decade. Among the various existing nanosystems, nanoparticles have the ability to transform conventional medicine by reducing the adverse effects and providing a controlled release of therapeutic agents. Also, their small size facilitates the intracellular uptake. Here, we provide a closer review of clinical prospects and mechanisms of action of nanomedicines to overcome drug resistance. The significance of specific targeting towards cancer cells is debated as well.

Targeted nanomedicines for the treatment of bone disease and regeneration.

Targeted delivery by either passive or active targeting of therapeutics to the bone is an attractive treatment for various bone related diseases such as osteoporosis, osteosarcoma, multiple myeloma, and metastatic bone tumors. Engineering novel drug delivery carriers can increase therapeutic efficacy and minimize the risk of side effects. Developmnet of nanocarrier delivery systems is an interesting field of ongoing studies with opportunities to provide more effective therapies. In addition, preclinical nanomedicine research can open new opportunities for preclinical bone-targeted drug delivery; nevertheless, further research is needed to progress these therapies towards clinical applications. In the present review, the latest advancements in targeting moieties and nanocarrier drug delivery systems for the treatment of bone diseases are summarized. We also review the regeneration capability and effective delivery of nanomedicines for orthopedic applications.

Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations.

Neuropsychiatric diseases are one of the main causes of disability, affecting millions of people. Various drugs are used for its treatment, although no effective therapy has been found yet. The blood brain barrier (BBB) significantly complicates drugs delivery to the target cells in the brain tissues. One of the problem-solving methods is the usage of nanocontainer systems. In this review we summarized the data about nanoparticles drug delivery systems and their application for the treatment of neuropsychiatric disorders. Firstly, we described and characterized types of nanocarriers: inorganic nanoparticles, polymeric and lipid nanocarriers, their advantages and disadvantages. We discussed ways to interact with nerve tissue and methods of BBB penetration. We provided a summary of nanotechnology-based pharmacotherapy of schizophrenia, bipolar disorder, depression, anxiety disorder and Alzheimer’s disease, where development of nanocontainer drugs derives the most active. We described various experimental drugs for the treatment of Alzheimer’s disease that include vector nanocontainers targeted on β-amyloid or tau-protein. Integrally, nanoparticles can substantially improve the drug delivery as its implication can increase BBB permeability, the pharmacodynamics and bioavailability of applied drugs. Thus, nanotechnology is anticipated to overcome the limitations of existing pharmacotherapy of psychiatric disorders and to effectively combine various treatment modalities in that direction.

Cell targeting strategy affects the intracellular trafficking of liposomes altering loaded doxorubicin release kinetics and efficacy in endothelial cells.

Targeting nanocarrier drug delivery systems, that deliver drug payloads to the site of disease action, are frequently viewed as the future of nanocarrier based therapies but have struggled to breakthrough to the clinic in comparison to non-targeting counterparts. Using unilamellar liposomes as model nanocarriers, we show that cell targeting strategy (electrostatic, ligand and antigen) influences both the intracellular fate of the liposomes and the corresponding efficacy of the loaded drug, doxorubicin, in endothelial cells. We show that increased liposome uptake by cells does not translate to improved efficacy in this scenario but that liposome intracellular trafficking, particularly distribution between recycling endosomes and lysosomes, influences in vitro efficacy. Choosing targeting strategies that promote desired nanocarrier intracellular trafficking may be a viable strategy to enhance the in vivo efficacy of drug delivery systems.

Ultrasound-mediated delivery enhances therapeutic efficacy of MMP sensitive liposomes

To improve therapeutic efficacy of nanocarrier drug delivery systems, it is essential to improve their uptake and penetration in tumour tissue, enhance cellular uptake and ensure efficient drug release at the tumour site. Here we introduce a tumour targeting drug delivery system based on the ultrasound-mediated delivery of enzyme sensitive liposomes. These enzyme sensitive liposomes are coated with cleavable poly(ethylene glycol) (PEG) which will be cleaved by two members of the enzyme matrix metalloproteinase family (MMP-2 and MMP-9). Cleavage of the PEG coat can increase cellular uptake and will destabilize the liposomal membrane which can result in accelerated drug release. The main aim of the work was to study the effect of focused ultrasound and microbubbles on the delivery and therapeutic efficacy of the MMP sensitive liposome. The performance of the MMP sensitive liposome was compared to a non-MMP sensitive version and Doxil-like liposomes. In vitro, the cellular uptake and cytotoxicity of the liposomes were studied, while in vivo the effect of ultrasound and microbubbles on the tumour accumulation, biodistribution, microdistribution, and therapeutic efficacy were investigated. For all tested liposomes, ultrasound and microbubble treatment resulted in an improved tumour accumulation, increased extravasation, and increased penetration of the liposomes from blood vessels into the extracellular matrix. Surprisingly, penetration depth was independent of the ultrasound intensity used. Ultrasound-mediated delivery of free doxorubicin and the Doxil-like and MMP sensitive liposome resulted in a significant reduction in tumour volume 28 days post the first treatment and increased median survival. The MMP sensitive liposome showed better therapeutic efficacy than the non-MMP sensitive version indicating that cleaving the PEG-layer is important. However, the Doxil-like liposome outcompeted the MMP and non-MMP sensitive liposome, both with and without the use of ultrasound and microbubbles.

Insights into Nanotherapeutic Strategies as an Impending Approach to Liver Cancer Treatment.

Liver cancer, being the utmost prevalent fatal malignancy worldwide, is ranked as the fifth leading cause of deaths associated with cancer. Patients with liver cancer are diagnosed often at an advanced stage, contributing to poor prognosis. Of all forms of liver cancer, hepatocellular carcinoma (HCC) contributes to 90% of cases, with chemotherapy being the treatment of choice. However, unfavorable toxicity of chemotherapy drugs and the vulnerability of nucleic acid-based drugs to degradation, have limited their application in clinical settings. So, in order to improvise their therapeutic efficacy in HCC treatment, various nanocarrier drug delivery systems have been explored. Furthermore, nanoparticle based imaging provides valuable means of accurately diagnosing HCC. Thus, in recent years, the advent of nanomedicine has shown great potential and progress in dramatically altering the approach to the diagnosis as well as treatment of liver cancer. Nanoparticles (NPs) are being explored as potential drug carriers for small molecules, miRNAs, and therapeutic genes used for liver cancer treatment. This review emphasizes on the current developments and applications of nanomedicine based therapeutic and diagnostic approaches in HCC.

PH- and temperature-responsive radially porous silica nanoparticles with high-capacity drug loading for controlled drug delivery

The design of smart and functional nanocarriers for drug delivery systems that use a variety of organic and inorganic materials has led to the development of nanomedicines with improved therapeutic efficiency and reduced side effects. In this study, a pH- and temperature-responsive, controlled-release system with a high capacity for drug loading was developed based on radially porous silica nanoparticles composed of functionalized ligands and polymer encapsulation. This drug delivery system uses radially oriented mesoporous silica nanoparticles as the drug carrier, and control of the surface chemistry of those nanocarriers allows high-capacity loading efficiency of target drugs and stimuli-responsive release kinetics governed by pH and temperature. The delivery of ibuprofen was chosen to test this system, and a maximum loading efficiency of ca. 270 wt% was established, which was 3 times greater than that in previous studies for silica nanoparticles such as SBA-15, MCA-41, and MCM-48. In addition, the pH- and temperature-responsive release of ibuprofen was achieved when the surface of the nanocarriers was treated by pH-responsive amine functionalization and a temperature-responsive surface coating of agarose gel. Finally, cytotoxicity testing using the fibroblast cells showed that the developed silica nanocarriers have no toxicity on the cells, which should allow these nanocarriers to be applied as a nanomedicine in drug delivery systems.

Dissipative Particle Dynamics Aided Design of Drug Delivery Systems: A Review.

A nanocarrier drug delivery system, effectively assisting to improve the solubility, bioavailability, and targeting of drugs in the human body, is a crucial means for treating cancer and other diseases. However, drug carriers usually possess multiple components and complex microstructures, and studies on the formation mechanism and internal structural details of nanocarriers are still incomplete by experimental methods. In order to overcome this adversity, the dissipative particle dynamics (DPD) simulation has been widely used owing to its unique simulation time-space scale and satisfying computing efficiency. In the past decades, more and more kinds of complex nanocarriers with various structures have been successfully characterized, and influencing factors in mounting numbers have also been parametrized. Not only emphasizing on the self-assembly structure of nanocarriers, but the application area of DPD simulation has also become a complete system covering from the synthesis and preparation to interaction with the biomembrane. This article reviews the application of DPD simulations in drug delivery systems. We have established the connection between existing studies and proposed some outlooks for the further combination between DPD simulation and the design of a drug delivery system.

Potential advancements of nanocarriers in topical drug delivery: a mini review

The topical route offers many attractive alternatives for the drug delivery as compared to oral administration and injection. Besides, skin provides a reservoir that delivers drug delivery for days. Nanotechnology, science at nano scale, has been emerged as a strong and potential discipline focusing on atom and molecular mechanisms that contributes to a diversity of applications in various fields such as controlled and targeted drug delivery, bio-imaging, agriculture, 3D printing, physics, mechanics, etc. Nanocarriers avoid local irritation and toxicity. The nanocarrier drug delivery system has emerged as interesting field that broaden up the use various drugs (lipophillic and hydrophilic) and provides ease of fabrication of formulations that can be efficiently delivered via topical route. The nanocarrier based delivery has been explored to deliver hydrophilic and lipophilic drug candidates through stratum corneum with local and systemic effects for the treatment of variety different skin diseases. Nanocarriers such as a nanoparticle, dendrimer, ethosome, and liposome are made up of polymers and material that differ in structure and chemical nature. These nanocarriers can deliver the drug at the target site and reduce side effects by lowering drug doses. This review covers all aspects of pharmaceutical nanocarriers related to their applications and recent advancements.

Evolution of Nanocarrier Drug-Delivery Systems and Recent Advancements in Covalent Organic Framework–Drug Systems

Nanotechnology has been actively employed in the development of drug-delivery systems overcoming the limitations of conventional carriers. In nanomedicine, the ultimate goal is to design and develo...

Advances and challenges in nanocarriers and nanomedicines for veterinary application.

To ensure success in the development and manufacturing of nanomedicines requires forces of an interdisciplinary team that combines medicine, engineering, chemistry, biology, material and pharmaceutical areas. Numerous researches in nanotechnology applied to human health are available in the literature. Althought, the lack of nanotechnology-based pharmaceuticals products for use exclusively in veterinary pharmacotherapy creates a potential area for the development of innovative products, as these animal health studies are still scarce when compared to studies in human pharmacotherapy. Nano-dosage forms can ensure safer and more effective pharmacotherapy for animals and can more be safer for the consumers of livestock products, once they can offer higher selectivity and smaller toxicity associated with lower doses of the drugs. In addition, the development and production of nanomedicines may consolidate the presence of pharmaceutical laboratories in the global market and can generate greater profit in a competitive business environment. To contribute to this scenario, this article provides a review of the main nanocarriers used in nanomedicines for veterinary use, with emphasis on liposomes, nanoemulsions, micelles, lipid nanoparticles, polymeric nanoparticles, mesoporous silica nanoparticles, metallic nanoparticles and dendrimers, and the state of the art of application of these nanocarriers in drug delivery systems to animal use. Finnaly, the major challenges involved in research, scale-up studies, large-scale manufacture, analytical methods for quality assessment, and regulatory aspects of nanomedicines were discussed.

A Review on Carbon Nanotubes: As a Nano carrier Drug Delivery System

Carbon nanotubes were discovered in 1991, Sumio Iijima gives the theory of carbon nanotubes which is made up of carbon allotrope graphene having brilliant electrical, mechanical, optical and synthetic properties, pulling in extensive enthusiasm for their application in different fields including drug conveyance and malignancy treatment. Malignancy is one of the most testing sicknesses of present day times since its treatment includes recognizing ordinary sound cells from influenced cells. Here, carbon nanotubes assume a significant job since marvels, for example, electronic paramagnetic resonance, permit carbon nanotubes to recognize typical cells from influenced ones, the Holy Grail in malignancy treatment. Significant work has been done on carbon nanotubes as medication conveyance frameworks throughout the most recent 20 y. Not with standing, worries over specific issues, for example, biocompatibility and poisonousness have been raised and warrant broad exploration in this field. For the preparation of Single-walled carbon nanotubes and Multi-walled carbon nanotubes arc discharge, laser ablation and chemical vapor deposition method of preparation are used. By the process of acid treatment, magnetic purification and size exclusion chromatography carbon nanotubes impurities are removed out. Because of hydrophobic nature of carbon nanotubes, Covalent and non-covalent functionalization are done for the surface modification. Cytotoxic of carbon nanotubes have a beneficial effect in cancer treatment. Drug released from carbon nanotubes by using various stimulants such as electric, magnetic field and changes in pH.

Green Nanotechnology-based Gold Nanomaterials for Hepatic Cancer Therapeutics: A Systematic Review

The objective of the current study was to systematically review the in-vitro anticancer activity of green synthesized gold nanoparticles (AuNPs) against hepatic cancer cells. The articles were identified through electronic databases, including PubMed, Scopus, Embase, Web of Science, Science Direct, ProQuest, and Cochrane. In total, 20 articles were found eligible to enter into our systematic review. Our findings showed that 65% of the articles used herbal extracts for the synthesis of AuNPs. Significantly, almost all of the articles stated the biofabrication of AuNPs below 100 nm in diameter. Impressively, most of the studies showed significant anticancer activity against HepG2 cells. Molecular studies stated the induction of apoptosis through the AuNPs-treated cells. We provided valuable information about the molecular mechanisms of AuNPs-induced cytotoxicity against HepG2 cells as well as their biocompatibility. The studies represented that AuNPs can be effective as anticancer drug nanocarrier for drug delivery systems. In addition, AuNP surface functionalization provides an opportunity to design multifunctional nanoparticles by conjugating them to diagnostic and/or therapeutic agents for theranostic purposes. Overall, our findings depicted considerable biogenic AuNPs-induced cytotoxicity, however, future studies should assess the anticancer activity of biogenic AuNPs through in-vivo studies, which was missing from such studies.

Application of Virus Targeting Nanocarrier Drug Delivery System in Virus-Induced Central Nervous System Disease Treatment.

Virus-induced central nervous system (CNS) diseases represent a significant burden to animal health worldwide. The difficulty in treating these diseases is mainly attributable to the elaborate barrier system, which limits the transport of drugs to the infected sites. Therefore, it is necessary to develop smart delivery technologies for treatment of these diseases. In the study, viral nervous necrosis disease was studied as a model to evaluate the feasibility of multiwalled carbon nanotubes (MWCNTs) conjugated with virus-specific nanobody and antiviral drug for targeted therapy of virus-induced CNS diseases. The virus (named as PGNNV) was isolated, identified and purified from diseased grouper. A naïve phage-displayed alpaca nanobody library was constructed, and the purified PGNNV was used for biopanning of PGNNV-specific nanobody from the library. The targeted delivery system based on MWCNTs conjugated with polyethylenimine, ribavirin, and PGNNV-specific nanobody was constructed and designated as MWCNTs-PEI-R-Nb. Targeting ability and treatment effects of the MWCNTs-PEI-R-Nb were checked both in vitro and in vivo. MWCNTs-PEI-R-Nb showed an increasing distribution in PGNNV-infected cells, and an obvious accumulation in the brain of PGNNV-infected zebrafish larvae. MWCNTs-PEI-R-Nb also showed a strong anti-PGNNV ability both in vitro and in vivo. The mortality of larvae treated with MWCNTs-PEI-R-Nb (equivalent to 100 mg/L ribavirin) was 27% during 10 days post infection, whereas it was 100% for the control group. The results so far indicate that MWCNTs conjugated with antiviral drugs and viral-specific antibody are effective means for virus-induced CNS disease targeted therapy.

Characterized and synthesis of chitosan nanoparticle as nanocarrier system technology

Chitosan is a natural material produced by deacetylation of chitin from crustacean exoskeleton. Being biocompatible, biodegradable, and affordable, chitosan is widely explored in biomedical field as active agent or drug carrier. Nanoparticles with its unique physicochemical properties, have great potential to maximize therapeutic efficacy. This study used chitosan nanoparticles made by ionotrophic gelation technique. The aim of this study was to characterized chitosan nanoparticles for particle size, surface morphology and degree of deacetylation. The chitosan nanoparticles diameter size was 48nm with polydispersity index was 0,289 and degree of deacetylation less than 75%. Therefore, chitosan nanoparticle is a promising nanocarrier system for drug delivery to enhance drug permeation.