Nanoparticle-based Drug Delivery Systems Research Articles

Designing Nanoparticle-based Drug Delivery Systems for Precision Medicine.

Traditional drugs are facing bottlenecks of lower solubility, absorption, and especially the inefficient organs or cells targeting during the precision medicine era. It is urgently needed to discover and establish new methods or strategies to modify old drugs or create new ones against the above defects. With the support of nanotechnology, the solubility, absorption and targeting of traditional drugs were greatly improved by modifying and fabricating with various types of nanoparticles to some extent, though many shortages remain. In this mini-review we will focus on advances in several most commonly used nanoparticles, from their nature and design, to drug delivery system and clinical application, that they overcome heterogeneous barriers in precision medicine, thereby ultimately improve patient outcome overall.

Efficient Targeted Therapy for Pancreatic Cancer Using Nanosystem and Focusing on the Suppression of Pancreatic Stellate Cell Activation

Introduction: Pancreatic cancer is characterized by remarkable desmoplasia which causes poor drug delivery and resistance to anticancer therapy. Pancreatic stellate cells (PSCs) play a key role in construction of such tumor environment and enhance the malignancy of pancreatic cancer cells. We have previously reported PSC activation was suppressed by inhibiting autophagy of PSC using a lysosomal inhibitor, chloroquine (CQ). However, CQ requires high dosage to be effective in vivo. In this study, we developed nanoparticle-based drug delivery system (DDS) and evaluated its availability in the tumor-bearing mouse model. Methods: Poly lactic-co-glycolic acid (PLGA) was used as a DDS carrier. The PLGA nanoparticles were loaded with ICG (Nano-ICG) or CQ (Nano-CQ). The accumulation of Nano-ICG in pancreatic tumor was evaluated by in vivoimaging system (IVIS). The effects of CQ, Nano-CQ, or the combination of these agents and gemcitabine (GEM) on the activation of PSC and tumor growth were investigated in the orthotopic xenograft mouse model. Results: Nano-ICG showed pancreatic tumor-specific accumulation and persisted for more than one week after administration. No obvious accumulation was observed in other major organs including liver, kidney, and normal pancreatic tissue. The fraction of activated PSC was significantly decreased in Nano-CQ group compared to the control group. The combination of Nano-CQ and GEM showed the best ability to restrain tumor progression among all the groups. Conclusion: Our PLGA-based nanosystem was considered to be a promising DDS for the treatment of pancreatic cancer and nano-CQ could enhance the efficacy of anticancer drugs.

Biomimetic nanomedicine toward personalized disease theranostics

Despite nanoparticle-based drug delivery systems have aroused broad research interest in the biomedical fields, the rising challenges such as easy recognition by the immune system and low accumulation in diseased sites significantly hinder their further clinical translation. Nanoparticles wrapped in cell membrane have emerged as a distinctive strategy to overcome these limitations due to the superior marriage of natural cell membrane and artificial nanomaterials, which endow them with prominent advantages in disease diagnosis and treatment, such as targeted drug transport, prolonged drug half-life, and diminished immunogenicity and cytotoxicity. In this review, we mainly highlight and discuss the evolving progresses and advantages of cell membrane-based biomimetic nanosystems in the detection and treatment of various diseases over the past five years, including oncology, bacterial infections, brain diseases, and inflammatory diseases, which would benefit researchers in better and comprehensively understanding the complicated microenvironment of diseases and developing personalized biomimetic nanomedicines for different diseases. The current challenges and potential opportunities for the future clinical translation of cell membrane coating nanotechnology are also covered.

Nanotheranostic agents for neurodegenerative diseases.

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

A potential hypothesis for 2019-nCoV infection therapy through delivery of recombinant ACE2 by red blood cell-hitchhiking

A novel infectious disease, caused by 2019 Novel Coronavirus (2019-nCoV) is responsible for the recent outbreak of severe respiratory disease. The 2019-nCoV spread rapidly and reaching epidemic proportions in many countries of the world. ACE2 was identified as a key receptor for 2019-nCoV infections. Excessive form of soluble ACE2 rescues cellular ACE2 activity which has a protective role in acute lung failure and neutralizes the virus. The short half-life of ACE2 is a major limitation to its practical application. Nanoparticle-based drug delivery systems are one of the most widely investigated approaches for developing novel therapies for a variety of diseases. Nevertheless, nanoparticles suffer from the rapid removal from the bloodstream by the reticuloendothelial system (RES). A noncovalent attachment of nanoparticles to RBCs increases their half-life in blood and allows transient accumulation in the lungs, while decreases their uptake by the liver and spleen. Connecting the recombinant ACE2 into the surface of nanoparticles that were attached to RBCs can be a potential therapeutic approach for 2019-nCoV infection through increasing their lung targeting to naturalize the virus and also acting as a bioreactor in the blood circulation to decrease serum level of Angiotensin II and protects lungs from injury/ARDS.

Nanoparticle-based therapeutics of inflammatory bowel diseases: a narrative review of the current state and prospects

Abstract Inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing disorders of the gastrointestinal tract. Characterized pathologically by intestinal inflammation and epithelial injury, great challenges exist for the treatment of IBD due to its complicated etiology and incurable nature. Traditional strategies rely on frequent and long-term administration of high dosages of anti-inflammatory drugs, which inevitably cause side effects. Therefore, novel therapeutic methods and drug delivery systems capable of improving therapeutic effect while simultaneously decreasing side effects need to be developed. The emergence of nanotechnology provides alternative approaches for diagnosis and treatment of IBD, as nanoparticles (NPs) have unique physicochemical properties such as targeting to the site of inflammation and the ability to alter the pharmacokinetics of traditional drugs. This review first introduces the pathophysiological features and microenvironment of IBD, and then summarizes different strategies and mechanisms of NP-based colon-targeted drug delivery systems, including size-dependent, multi-stimuli responsive, active targeting, intestinal microbiota-related, and novel natural-derived NP-mediated drug delivery systems. We also discuss applications of nanozymes and NP-based imaging in diagnostics and treatment of IBD. Finally, challenges and prospects in the field are proposed to promote the development of targeted drug delivery for IBD treatment.

Platelet-Mimicking Drug Delivery Nanoparticles for Enhanced Chemo-Photothermal Therapy of Breast Cancer.

BackgroundTraditional nanoparticle-based drug delivery systems suffer from several limitations, such as easy clearance from blood and inaccurate targeting.Materials and MethodsHere, we developed platelet membrane-coated nanoparticles (PM-NPs) to improve the precise delivery of drugs to tumor sites and enable a more efficient photothermal therapy (PTT) treatment.ResultsMimicking the natural platelet membrane, nanoparticles containing drugs and photothermal agents were not recognized and cleared by the immune system; they could circulate in the blood for a long time and accumulate more efficiently at the tumor site, thus releasing more antitumor drugs and achieving better PTT effects. It is worth mentioning that, in this study, we found that tumors in mice treated with the platelet-mimicking nanoparticles were completely eliminated without recurrence during the observation period (up to 18 days).ConclusionThis study provides a new strategy to design delivery systems of drugs or photothermal agents, whether in biotherapy or other fields.

Development, Characterization and Pharmacokinetic Profile of Chitosan-Sodium Tripolyphosphate Nanoparticles Based Drug Delivery Systems for Curcumin.

Purpose: This study aimed to provide the method of preparation, characterization of curcumin-loaded chitosan-sodium tripolyphosphate (NaTPP) nanoparticle, and evaluate its pharmacokinetic profiles. Methods: Curcumin-loaded chitosan-NaTPP nanoparticles were synthesized using ionic gelation methods. Curcumin was dissolved using surfactants and cosurfactants. Chitosan polymer was then mixed in the curcumin solution and dripped with NaTPP solution until nanoparticle formation. The mucoadhesive study was evaluated by measuring the fluorescence of curcumin within the prepared nanoparticles. The pharmacokinetic profiles of curcumin particles and nanoparticles were then assessed in rats by administering a single oral dose of 100 mg/kg BW. Blood samples were taken from nine predetermined time points, and curcumin plasma concentrations were then analyzed using UPLC-MS/MS. Results: The particle size of the curcumin nanoparticles obtained were 11.5 nm. Entrapment efficiency (EE) of curcumin nanoparticles were exceeding 99.97%, and drug loading capacity (DLC) was 11.34%. The mucoadhesive properties of the nanoparticles were superior to that of curcumin particles. Pharmacokinetic evaluation in rats revealed that curcumin nanoparticles resulted in an increase of area under the curve (AUC), maximum concentration (Cmax), earlier time to reach maximum concentration (Tmax), and lower clearance (CL). Conclusion: Curcumin-loaded chitosan-NaTPP nanoparticles is an effective formulation to improve curcumin plasma concentrations. Thus, enable its applications for the treatment of various diseases.

Adriamycin/Nucleophosmin Binding Protein-Conjugated Nanoparticle (ADR-PMs-NPMBP) Enhances Anti-Leukemia Activities of Adriamycin in Acute Lymphoblastic Leukemia Cells

Acute lymphoblastic leukemia (ALL) is an aggressive malignancy. Adults with ALL have more than 50% relapse rates and 20-40% overall survival. We previously validated that overexpression of NPM may be involved in the multidrug resistance development and might be important indicator for prognosis evaluation in ALL. In this study, we engineered and synthesized recombinant NPM binding protein (NPMBP). NPMBP and adriamycin (ADR) were bound to polymeric nanoparticle-based drug delivery system and named ADR-PMs-NPMBP (China Patent Application 202010302395.6, 202010739575.0). In this study, we aimed to evaluate thein vitroandin vivoanti-leukemia activity of ADR-PMs-NPMBP in resistant ALL cells. The underlying mechanisms were further addressed. In vitrostudy data demonstrated that ADR-PMs-NPMBP significantly enhanced chemosensitivity of ALL cells to ADR. The IC50 values of ADR-PMs-NPMBP in 4 ALL cell lines and primary ALL cells from 6 patients were between 1.6- and 7.0-fold lower than those of ADR. Of note, all the resistant ALL cell lines and the primary ALL cells from the relapsed patients, although variable in degree, were sensitive to ADR-PMs-NPMBP. The ratio of apoptosis cells in resistant ALL cells was more than 2-fold as compared ADR-PMs-NPMBP with single ADR regimen. RNA-seq analysis showed that there were 5599 and 233 differentially expressed genes in ADR-PMs-NPMBP versus control and ADR-PMs-NPMBP versus ADR comparison groups, respectively. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that 21 pathways play significant roles in ADR-PMs-NPMBP-mediated anti-leukemia activities in ALL. Of note, p53 protein with gene symbol TP53 was interestingly identified to overlap in the 5 pathways as following: Epstein-Barr virus infection, cell cycle, apoptosis, human T-cell leukemia virus 1 infection and p53 signaling pathway. Further validation experiments showed that ADR-PMs-NPMBP-induced effects on cell viability were due to the multiple roles of the activated p53 in apoptosis induction and cell cycle arrest. In vivostudy showed that ADR-PMs-NPMBP regimen was well tolerated by both resistant ALL xenograft BALB/C-nude model and ALL cell transplanted NOD-Prkdcem26Il2rgem26Nju (NCG) model. No systemic toxicity occurrence was observed after the recipients were intraperitoneally administered with ADR-PMs-NPMBP at 25 mg/kg/day for 3 days. The body weights of the animals increased with the time in both tumor model systems. Of note, whole-body bioluminescence imaging showed that less tumor cell burden was observed in ADR-PMs-NPMBP-treated recipients as compared to the animals administered with ADR. The tumor inhibition rate achieved as high as 79.2% in ADR-PMs-NPMBP group when finished the following-up. Moreover, studies on NCG model showed that ADR-PMs-NPMBP conditioning sensitized the antileukemia response of the resistant ALL xenograft model to ADR. Wright-Giemsa staining results demonstrated that more mature myeloid cells and lymphocytes were presented in the bone marrow samples from ADR-PMs-NPMBP-conditioned mice. In contrast, the increased immature blast cells were observed in the bone marrow from vehicle control mice and ADR-treated mice. Notably, the regimen of ADR-PMs-NPMBP diminished or blocked simultaneous metastases to multiple organs including liver and spleen, and significantly prolonged mouse survival. In conclusion, our study provides the first evidence that ADR-PMs-NPMBP nanoparticle may exert apoptotic inductionviathe activation of p53 pathway and markedly improve the antileukemia effect of ADR in resistant ALL cellsin vitroandin vivo. Our data indicate that the novel drug delivery system may be valuable to develop as a new strategy for the treatment of ALL, particularly for the resistant ALL. Disclosures No relevant conflicts of interest to declare.

Silk Particles as Carriers of Therapeutic Molecules for Cancer Treatment.

Although progress is observed in cancer treatment, this disease continues to be the second leading cause of death worldwide. The current understanding of cancer indicates that treating cancer should not be limited to killing cancer cells alone, but that the target is the complex tumor microenvironment (TME). The application of nanoparticle-based drug delivery systems (DDS) can not only target cancer cells and TME, but also simultaneously resolve the severe side effects of various cancer treatment approaches, leading to more effective, precise, and less invasive therapy. Nanoparticles based on proteins derived from silkworms’ cocoons (like silk fibroin and sericins) and silk proteins from spiders (spidroins) are intensively explored not only in the oncology field. This natural-derived material offer biocompatibility, biodegradability, and simplicity of preparation methods. The protein-based material can be tailored for size, stability, drug loading/release kinetics, and functionalized with targeting ligands. This review summarizes the current status of drug delivery systems’ development based on proteins derived from silk fibroin, sericins, and spidroins, which application is focused on systemic cancer treatment. The nanoparticles that deliver chemotherapeutics, nucleic acid-based therapeutics, natural-derived agents, therapeutic proteins or peptides, inorganic compounds, as well as photosensitive molecules, are introduced.

Homotype-Targeted Biogenic Nanoparticles to Kill Multidrug-Resistant Cancer Cells

“Off-targeting” and receptor density expressed at the target sites always compromise the efficacy of the nanoparticle-based drug delivery systems. In this study, we isolated different cell membranes and constructed cell membrane-cloaked biogenic nanoparticles for co-delivery of antitumor paclitaxel (PTX) and multidrug resistance (MDR)-modulator disulfiram (DSF). Consequently, MDR cancer cell membrane (A549/T)-coated hybrid nanoparticles (A549/T CM-HNPs) selectively recognized the source cells and increased the uptake by ninefold via the homotypic binding mechanism. Moreover, the A549/T CM-HNPs sensitized MDR cells to PTX by suppressing P-glycoprotein (P-gp) activity by 3.2-fold and induced effective apoptosis (70%) in homologous A549/T cells. Cell-membrane coating based on the “homotypic binding” is promising in terms of promoting the accumulation of chemotherapeutics in MDR cells and killing them.

Potential antibiofilm activity of farnesol-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles against Candida albicans

Candida species are ubiquitous fungal pathogens and are the most common causes of mucosal and invasive fungal infections in humans. Especially Candida albicans commonly resides as a commensal in the mucosal tissues of approximately half of the human population. When the balance of the normal flora is disrupted or the immune defenses are compromised, Candida species can become pathogenic, often causing recurrent disease in susceptible individuals.The treatments available for Candida infection are commonly drug-based and can involve topical and systemic antifungal agents. However, the use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. Candida species ability to produce drug-resistant biofilm is an important factor in human infections, because microorganisms within biofilm benefit from various advantages over their planktonic counterparts including protection from antimicrobials and chemicals. These limitations emphasize the need to develop new and more effective antifungal agents. Natural products are attractive alternatives for this purpose due to their broad spectrum of biological activities. Farnesol is produced by many microorganisms and found in some essential oils. It has also a great attention as a quorum-sensing molecule and virulence factor. It has also antimicrobial potential due to its inhibitory effects on various bacteria and fungi. However, as it is a hydrophobic component, its solubility and biofilm inhibiting properties are limited.To overcome these shortcomings, nanoparticle-based drug delivery systems have been successfully used. For this purpose, especially using biodegradable polymeric nanoparticles has gained increasing attention owing to their biocompatibility and minimal toxicity. Poly (DL-lactide-co-glycolide) (PLGA) is the most widely used polymer in this area. In this study, farnesol is loaded to PLGA nanoparticles (F-PLGA NPs) by emulsion evaporation method and characterized by DLS, TEM, and FT-IR analyses. Our TEM findings indicate that the sizes of F-PLGA NPs are approximately 140 nm. The effects of F-PLGA NPs on planktonic cells and biofilm formation of C. albicans were compared with effects of farnesol alone. Farnesol inhibits the growth at a range of 53% at a concentration of 2.5 μL compared to the control group. This rate is 45% for F-PLGA NPs at the same concentration. However, although farnesol amount in F-PLGA is approximately 22.5% of the total volume, the observed effect is significant. In TEM examinations, planktonic Candida cells treated with farnesol showed relatively regular ultrastructural morphology. Few membrane and wall damage and electron density in the cytoplasm were determined. In F-PLGA NP-treated cells, increased irregular cell morphology, membrane and wall damages, and large vacuoles are observed. Our SEM and XTT data suggest that F-PLGA NPs can reduce the biofilm formation at lower concentrations than farnesol alone 57%, and our results showed that F-PLGA NPs are effective and biocompatible alternatives for inhibiting growth and biofilm formation of C. albicans, but detailed studies are needed.

Micelles self-assembled by 3-O-\u03b2-d-glucopyranosyl latycodigenin enhance cell membrane permeability, promote antibiotic pulmonary targeting and improve anti-infective efficacy

BackgroundNanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. However, developing the formulation of each drug is a time-consuming and laborious task.ResultsIn this study, a universal lung-targeting nanoparticle was designed and constructed. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-d-glucopyranosyl platycodigenin 682 (GP-682), based on its specific amphiphilic structure. The GP-682 micelles exhibited a relatively stable zeta potential with a particle size between 60 and 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 μg/mL. Preincubation of GP-682 micelles markedly enhanced their cell membrane permeability and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. The acute lung injury mouse model induced by the Pseudomonas aeruginosa PA 14 strain demonstrated that preinjection of GP-682 micelles before antibiotic administration resulted in a higher survival rate and anti-infective efficacy in vivo. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone.ConclusionsGP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provide a new lung-targeting therapy option.

Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy

This review summarizes the epigenetic mechanisms of deoxyribonucleic acid (DNA) methylation, histone modifications in cancer and the epigenetic modifications in cancer therapy. Due to their undesired side effects, the use of epigenetic drugs as chemo-drugs in cancer therapies is limited. The drug delivery system opens a door for minimizing these side effects and achieving greater therapeutic benefits. The limitations of current epigenetic therapies in clinical cancer treatment and the advantages of using drug delivery systems for epigenetic agents are also discussed. Combining drug delivery systems with epigenetic therapy is a promising approach to reaching a high therapeutic index and minimizing the side effects.

Doxorubicin Loaded Nanoparticle Consisting of Chitosan and Mannose Modified Graphene Oxide for Intracellular Drug Delivery and Anti-tumor Activity

In order to develop the efficiency and the specificity of anticancer drug delivery, we have designed an innovative nanocarrier. The nanocarrier system comprises of a multifunctional graphene oxide nanoparticle-based drug delivery system (GO-CS-M-DOX) as a novel platform for intracellular drug delivery of doxorubicin (DOX). Firstly, graphene oxide (GO) was synthesized by hummer’s method whose surface was functionalized by chitosan (CS) in order to obtain a more precise drug delivery, the system was then decorated with mannose (M). Further conjugation of an anti-cancer drug doxorubicin to the nanocarrier system resulted in GO-CS-M-DOX drug delivery system. The resultant conjugate was characterized for its physio-chemical properties and its biocompatibility was evaluated via hemolysis assay. The drug entrapment efficiency is as high as 90% and in vitro release studies of DOX under pH 5.3 is significantly higher than that under pH 7.4. The anticancer activity of the synthesized drug delivery system was studied by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay against MCF-7 cell line. These results stated that the pH dependent multifunctional doxorubicin- chitosan functionalized graphene oxide based nanocarrier system, could lead to a promising and potential platform for intracellular delivery and cytotoxicity activity for variety of anticancer drugs. 

Visible Light-Activated Water-Soluble Platicur Nanocolloids: Photocytotoxicity and Metabolomics Studies in Cancer Cells.

Nanoparticle-based drug delivery systems for cancer therapy offer a great promising opportunity as they specifically target cancer cells, also increasing the bioavailability of anticancer drugs characterized by low water solubility. Platicur, [Pt(cur) (NH3)2](NO3), is a cis-diamine-platinum(II) complex linked to curcumin. In this work, an ultrasonication method, coupled with layer by layer technology, allows us to obtain highly aqueous stable Platicur nanocolloids of about 100 nm. The visible light-activated Platicur nanocolloids showed an increased drug release and antitumor activity on HeLa cells, with respect to Platicur nanocolloids in darkness. This occurrence could give very interesting insight into selective activation of the nanodelivered Pt(II) complex and possible side-effect lowering. For the first time, the metabolic effects of Platicur nanocolloid photoactivation, in the HeLa cell line, have been investigated using an NMR-based metabolomics approach coupled with statistical multivariate data analysis. The reported results highlight specific metabolic differences between photoactivated and non-photoactivated Platicur NC-treated HeLa cancer cells.

Nitric Oxide Nano-Delivery Systems for Cancer Therapeutics: Advances and Challenges.

Nitric oxide (NO) plays important roles in various physiological and pathological functions and processes in the human body. Therapeutic application of NO molecules has been investigated in various diseases, including cardiovascular disease, cancer, and infections. However, the extremely short half-life of NO, which limits its clinical use considerably, along with non-specific distribution, has resulted in a low therapeutic index and undesired adverse effects. To overcome the drawbacks of using this gaseous signaling molecule, researchers in the last several decades have focused on innovative medical technologies, specifically nanoparticle-based drug delivery systems (DDSs), because these systems alter the biodistribution of the therapeutic agent through controlled release at the target tissues, resulting in a significant therapeutic drug effect. Thus, the application of nano-systems for NO delivery in the field of biomedicine, particularly in the development of new drugs for cancer treatment, has been increasing worldwide. In this review, we discuss NO delivery nanoparticle systems, with the aim of improving drug delivery development for conventional chemotherapies and controlling multidrug resistance in cancer treatments.

Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance.

Nanotechnology has been extensively studied and exploited for cancer treatment as nanoparticles can play a significant role as a drug delivery system. Compared to conventional drugs, nanoparticle-based drug delivery has specific advantages, such as improved stability and biocompatibility, enhanced permeability and retention effect, and precise targeting. The application and development of hybrid nanoparticles, which incorporates the combined properties of different nanoparticles, has led this type of drug-carrier system to the next level. In addition, nanoparticle-based drug delivery systems have been shown to play a role in overcoming cancer-related drug resistance. The mechanisms of cancer drug resistance include overexpression of drug efflux transporters, defective apoptotic pathways, and hypoxic environment. Nanoparticles targeting these mechanisms can lead to an improvement in the reversal of multidrug resistance. Furthermore, as more tumor drug resistance mechanisms are revealed, nanoparticles are increasingly being developed to target these mechanisms. Moreover, scientists have recently started to investigate the role of nanoparticles in immunotherapy, which plays a more important role in cancer treatment. In this review, we discuss the roles of nanoparticles and hybrid nanoparticles for drug delivery in chemotherapy, targeted therapy, and immunotherapy and describe the targeting mechanism of nanoparticle-based drug delivery as well as its function on reversing drug resistance.

In Vitro Release Study of the Polymeric Drug Nanoparticles: Development and Validation of a Novel Method.

The in vitro release study is a critical test to assess the safety, efficacy, and quality of nanoparticle-based drug delivery systems, but there is no compendial or regulatory standard. The variety of testing methods makes direct comparison among different systems difficult. We herein proposed a novel sample and separate (SS) method by combining the United States Pharmacopeia (USP) apparatus II (paddle) with well-validated centrifugal ultrafiltration (CU) technique that efficiently separated the free drug from nanoparticles. Polymeric drug nanoparticles were prepared by using a four-stream multi-inlet vortex mixer with d-α-tocopheryl polyethylene glycol 1000 succinate as a stabilizer. Itraconazole, cholecalciferol, and flurbiprofen were selected to produce three different nanoparticles with particle size <100 nm. By comparing with the dialysis membrane (DM) method and the SS methods using syringe filters, this novel SS + CU technique was considered the most appropriate in terms of the accuracy and repeatability to provide the in vitro release kinetics of nanoparticles. Interestingly, the DM method appeared to misestimate the release kinetics of nanoparticles through separate mechanisms. This work offers a superior analytical technique for studying in vitro drug release from polymeric nanoparticles, which could benefit the future development of in vitro-in vivo correlation of polymeric nanoparticles.

Recent Advances in Treatment of Lung Cancer: Nanoparticle-based Drug and siRNA Delivery Systems.

Lung cancer is the second most diagnosed cancer in both men and women worldwide. Considering the high mortality rate of lung cancer and inadequacy of conventional treatment methods such as surgical resection, chemotherapy and radiotherapy; new treatment strategies are an emerging area of interest. Nanoparticle-based drug and small interfering RNA delivery systems such as lipid, polymeric, inorganic, micellar and dendrimer nanoparticles are designed to enhance the bioavailability, stability and retention of anti-cancer drugs in the targeted regions of the lung. These nanoparticle-based delivery systems increase the active ingredient half-life and targeting efficiency while reducing the required dose of the drug. Hence, they have many advantages such as higher therapeutic efficacy and reducedside effects and adverse events. Combinations of active ingredients, anti-cancer agents and small interfering RNA can be formulated into nanoparticle-based delivery systems that can be administered by various routes including inhalation and intravenous. In this review, the development of lipidic and polymeric nanoparticle-based drug and small interfering RNA delivery systems used in the treatment of lung cancer is discussed.