Nanoparticle-based Drug Delivery Systems Research Articles

Engineering nanoparticles to overcome the mucus barrier for drug delivery: Design, evaluation and state-of-the-art

Mucus is a viscoelastic hydrogel that lubricates and protects mucosal tissues such as the eyes, lung, gastrointestinal tract, and vagina. Nanoparticle-based drug delivery systems (DDSs) can be easily trapped in the mucus network by steric obstruction and/or binding interactions and then are efficiently cleared away with rapid mucus turnover, thereby limiting mucosal drug delivery efficacy. Modulating the physicochemical properties of nanoparticles (NPs), including size, surface hydrophilicity and charge, shape, and rigidity, is an effective method to overcome the mucus barrier. This review first describes the protective barrier properties of mucus and how mucus affects the fate of NPs. It then reviews the techniques for evaluating particle movement in mucus, including macroscopic diffusivity and microcosmic diffusion mechanisms. The state-of-the-art strategies exploited by researchers to overcome the mucus barrier by using NPs are discussed. Finally, the dilemma and solutions of balancing both mucus penetration and cellular uptake barriers are discussed.

Nanoparticle-Based Drug Delivery System—A Target Strategy for Osteoarthritis Treatment

Osteoarthritis (OA) is a bone and joint disease with pathological characteristics such as articular cartilage degeneration injury and synovial and subchondral bone reactive hyperplasia. Once cartilage is damaged, it is difficult to repair it by itself. Current clinical practice is mainly limited to symptomatic treatment, not changing the degenerative process of osteoarthritis. The important goal of nanomedicine is targeted delivery. Nanoparticles (NPs) can provide many unique potential functions for the targeted treatment of arthritis. This review summarizes the research progress of nanomaterials as a drug delivery system in the treatment of osteoarthritis from three aspects: (1) the etiology of OA and the current research status of applying nanoparticles to treat OA, (2) the construction of osteoarthritis models, and (3) the classification of nanoparticle-based drug delivery systems.

Emerging trends in the delivery of nanoformulated oxytocin across Blood-Brain barrier

Neurological diseases are related to the central nervous system disorders and considered as serious cases. Several drugs are used to treat neurological diseases; however, to date the main issue is to design a therapeutic model which can cross the blood–brain-barrier (BBB) easily. The delivery of neuropeptides into the brain lays as one of the important routes for treating neurological disorders. Neuropeptides have been demonstrated as potential therapeutics for neurological disorders. Among numerous neuropeptides, the oxytocin (OT) hormone is of particular interest as it serves as a neurotransmitter in the brain as well as its role as a hormone. OT has a wide-range of activities in the brain and has a key role in cognitive, neuroendocrine, and social functions. However, OT does not cross the BBB readily coupled with its half-life in the blood being too short. The current literature reveals that the delivery of OT by nanoparticle-based drug delivery system (DDS) improves its efficacy. Nanoparticle based DDS are considered important tools for the targeted delivery of drugs to the brain as they lower toxicity of the drug and improve the drug efficacy. Nanoparticles are advantageous candidates for biomedical applications due to their distinctive characteristics such as quantum effects, large surface area and their ability to carry and transport the drug to its target site. OT can be delivered through oral and intranasal routes, but the bioavailability of OT inside the brain can further be enhanced by the delivery using nanoparticles. The application of nano-based delivery system not only improves the penetration of OT inside brain but also increases its half-life by the application of encapsulation and extended release. The aim of current review is to provide an overview of nanoparticle-based drug-delivery systems for the delivery of OT inside brain.

Organosilica colloids as nitric oxide carriers: Pharmacokinetics and biocompatibility

Nitric oxide (NO) is a potential therapeutic agent for various diseases. However, it is challenging to deliver this unstable, free-radical gaseous molecule in the body. Various nanoparticle-based drug delivery systems have been investigated as promising NO carriers without detailed characterization of their biological fate. The purpose of this study is to investigate the pharmacokinetics and biocompatibility of organosilica-based NO-delivering nanocarriers. Two distinct NO nanoformulations, namely NO-SiNP-1 and NO-SiNP-2, were prepared from a thiol-functionalized organosilane using nanoprecipitation and direct aqueous synthesis, respectively. During the preparation, the thiol group was converted to S-nitrosothiol (SNO) under a nitrosation condition. The final products contain SNO-loaded organosilica particles of similar sizes (~130 nm), but of different morphologies and surface charges (between the two formulations). In the in vitro release kinetics study, NO-SiNP-1 exhibited a much slower NO release rate than NO-SiNP-2 (by 5-fold); therefore, the former is considered as a slow NO releaser, and the latter a fast NO releaser. However, in the rat pharmacokinetic study (IV bolus of 50 μmol/kg), NO-SiNP-1 was rapidly eliminated from the blood (within 20 min); in contrast, NO-SiNP-2 was slowly eliminated with an extended circulation time of 12 h for plasma SNO, along with markedly higher plasma levels of nitrite and nitrate. The two formulations are generally biocompatible. In conclusion, the paper presents contrast biological fates of two organosilica colloidal formulations for nitric oxide delivery.

Design and Optimization of the Circulatory Cell-Driven Drug Delivery Platform.

Achievement of high targeting efficiency for a drug delivery system remains a challenge of tumor diagnoses and nonsurgery therapies. Although nanoparticle-based drug delivery systems have made great progress in extending circulation time, improving durability, and controlling drug release, the targeting efficiency remains low. And the development is limited to reducing side effects since overall survival rates are mostly unchanged. Therefore, great efforts have been made to explore cell-driven drug delivery systems in the tumor area. Cells, particularly those in the blood circulatory system, meet most of the demands that the nanoparticle-based delivery systems do not. These cells possess extended circulation times and innate chemomigration ability and can activate an immune response that exerts therapeutic effects. However, new challenges have emerged, such as payloads, cell function change, cargo leakage, and in situ release. Generally, employing cells from the blood circulatory system as cargo carriers has achieved great benefits and paved the way for tumor diagnosis and therapy. This review specifically covers (a) the properties of red blood cells, monocytes, macrophages, neutrophils, natural killer cells, T lymphocytes, and mesenchymal stem cells; (b) the loading strategies to balance cargo amounts and cell function balance; (c) the cascade strategies to improve cell-driven targeting delivery efficiency; and (d) the features and applications of cell membranes, artificial cells, and extracellular vesicles in cancer treatment.

Deciphering the role of nanoparticles for management of bacterial meningitis: an update on recent studies.

Meningitis is an inflammation of the protective membranes called meninges and fluid adjacent the brain and spinal cord. The inflammatory progression expands all through subarachnoid space of the brain and spinal cord and occupies the ventricles. The pathogens like bacteria, fungi, viruses, or parasites are main sources of infection causing meningitis. Bacterial meningitis is a life-threatening health problem that which needs instantaneous apprehension and treatment. Nesseria meningitidis, Streptococcus pneumoniae, and Haemophilus flu are major widespread factors causing bacterial meningitis. The conventional drug delivery approaches encounter difficulty in crossing this blood-brain barrier (BBB) and therefore are insufficient to elicit the desired pharmacological effect as required for treatment of meningitis. Therefore, application of nanoparticle-based drug delivery systems has become imperative for successful dealing with this deadly disease. The nanoparticles have ability to across BBB via four important transport mechanisms, i.e., paracellular transport, transcellular (transcytosis), endocytosis (adsorptive transcytosis), and receptor-mediated transcytosis. In this review, we reminisce distinctive symptoms of meningitis, and provide an overview of various types of bacterial meningitis, with a focus on its epidemiology, pathogenesis, and pathophysiology. This review describes conventional therapeutic approaches for treatment of meningitis and the problems encountered by them while transmitting across tight junctions of BBB. The nanotechnology approaches like functionalized polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, nanoemulsion, liposomes, transferosomes, and carbon nanotubes which have been recently evaluated for treatment or detection of bacterial meningitis have been focused. This review has also briefly summarized the recent patents and clinical status of therapeutic modalities for meningitis.

Antifungal and antibiofilm efficacy of cinnamaldehyde-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles against Candida albicans.

Biofilm-associated Candida infections threaten public health and show high mortality. The drugs used in treatment are very limited due to reasons such as toxicity, low efficacy, and drug resistance, and new alternatives are needed. The use of natural products of plant origin in the biofilm management draws attention. CA (cinnamaldehyde, cinnamic aldehyde, or 3-phenyl-2-propenal) is an essential oil component that can also inhibit mold growth and mycotoxin production. However, there are some limitations in its use due to its poor solubility and volatility in water. Recently, the combination of natural components and nanoparticle-based drug delivery systems shows positive results. In this study, the effects of PLGA (poly(DL-lactide-co-glycolide)) nanoparticles arrested with CA (CA-PLGA NPs) on C. albicans planktonic and biofilm forms (prebiofilm and postbiofilm) were investigated. According to the results, the amount of active ingredient loaded in CA-PLGA NPs is much lower than the free CA and a strong antifungal effect was obtained even at this rate. Also, the postbiofilm application is more effective than prebiofilm application. PLGA NPs can also be a useful carrier for other essential oils, and their potential in various antifungal, antibiofilm, and biomedical applications should be investigated.

Polymeric Fe<sub>3</sub>O<sub>4</sub> Conjugates with Bioactive Plant Molecules: Platforms for Antimicrobial Therapy

The emerging nano biosystems are competent in diagnosis, drug delivery, and monitoring of therapeutic response. Both imaging and therapeutic functions can be achieved by using nanoplatforms. These nanoplatforms promise to revolutionize the medical management of many personalized illnesses. The well-developed surface chemistry of iron oxide (Fe3O4) makes it easy to charge them with pharmaceutics, promoting them as nanoplatforms for building up nanoparticle-based drug delivery systems. The strategy to design multifunctional Fe3O4 conjugates with bioactive molecules of plant origin to show enhanced activity is reported here. The conjugation reveals the magnetic Fe3O4 core nanoparticle surface readily link to hydroxyl sites of the Dextrin molecule, which further conjugate to conjugated with Curcumin and D-Limonene, which are powerful anti-cancer, anti-inflammatory, and antioxidant agents. The structural, morphological, optical, and magnetic properties were analyzed by X-ray diffraction, FT-Infrared, HR-Tunneling Electron Microscopy, and Vibrating Sample Magnetometer techniques. The potential drug loading was measured as Drug Entrapment Efficiency using UV-Vis spectroscopy. The antibacterial property was tested on the bacterium S. aureus and E. coli. Fe3O4-Dextrin nanoconjugates proved to be efficient for loading and stabilizing Curcumin and Limonene. Thus, multifunctional Fe3O4 conjugates are explored as exciting nano-drug carriers for targeted drug delivery.

A dual-sensitive poly(amino acid)/hollow mesoporous silica nanoparticle-based anticancer drug delivery system with a rapid charge-reversal property

The negative-to-positive surface charge-reversal capability introduced can reduce the nonspecific cellular uptake of the nanosized anticancer drug delivery systems (DDSs) and enhance the endocytosis capability by cancer cells. In this article, a novel dual-sensitive anticancer DDS with a rapid charge-reversal property was reported. Hollow mesoporous silica nanoparticle (HMSN) with a high drug loading capacity was applied as the “nanocontainer” to package the drug doxorubicin hydrochloride (DOX), then was coated by poly(aspartic acid)-graft-1-(3-aminopropyl) imidazole (PASP-g-API) through the redox-sensitive disulfide bond to obtain the DDS DOX@HMSN–SS–PASP-API. The imidazole group was not ionized at pH 7.4, resulting in a negatively charged surface of the DDS. But in the slightly acidic tumor microenvironment, the ionization of the imidazole group rapidly reversed the surface charge of the carriers for better uptake by cancer cells. After the endocytosis, the disulfide bond linking PASP-g-API and HMSN could be interrupted in the reducing environment intercellular, leading to the DOX release. The rapid charge-reversal property of the carriers was demonstrated by the in vitro studies, and the cell experiments proved that the carriers could enter the cancer cells much easier in the weakly acidic environment. Drug release studies indicated that DOX@HMSN–SS–PASP-API could release ~97% loaded DOX within 5 days with the glutathione concentration of 10 mM, demonstrating its sensitivity to redox. Also, DOX@HMSN–SS–PASP-API at pH 6.5 showed the best therapeutic effect among all the DDS groups. This dual-sensitive system with a rapid charge-reversal property should be a good complement to the researches of anticancer DDSs.

Nanocarriers as a Tool for the Treatment of Colorectal Cancer.

Nanotechnology is a promising tool for the treatment of cancer. In the past decades, major steps have been made to bring nanotechnology into the clinic in the form of nanoparticle-based drug delivery systems. The great hope of drug delivery systems is to reduce the side effects of chemotherapeutics while simultaneously increasing the efficiency of the therapy. An increased treatment efficiency would greatly benefit the quality of life as well as the life expectancy of cancer patients. However, besides its many advantages, nanomedicines have to face several challenges and hurdles before they can be used for the effective treatment of tumors. Here, we give an overview of the hallmarks of cancer, especially colorectal cancer, and discuss biological barriers as well as how drug delivery systems can be utilized for the effective treatment of tumors and metastases.

Advanced Nanoparticle-Based Drug Delivery Systems and Their Cellular Evaluation for Non-Small Cell Lung Cancer Treatment.

Simple SummaryNanoparticulate systems have been extensively explored for the treatment of various diseases, including cancers. The outstanding characteristics of nanoparticles have made it possible to administer them via different routes such as intravenous or inhalation. This flexibility can improve the delivery of encapsulated drugs to the targeted cells for the treatment of lung-related diseases and cancers such as non-small cell lung cancers. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. As the handling of in vivo models is a challenge, many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. This review focuses on the currently available nanoparticles for lung cancers and the type of cellular work that can be conducted to evaluate the effectiveness of a nanoparticulate system for this cancer type.Lung cancers, the number one cancer killer, can be broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC being the most commonly diagnosed type. Anticancer agents for NSCLC suffer from various limitations that can be partly overcome by the application of nanomedicines. Nanoparticles is a branch within nanomedicine that can improve the delivery of anticancer drugs, whilst ensuring the stability and sufficient bioavailability following administration. There are many publications available in the literature exploring different types of nanoparticles from different materials. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. This includes the developed nanoparticles, to prove their safety and efficacy. Many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. However, in cellular works, the physiological dynamics that is available in the body could not be mimicked entirely, and hence, there is still possible development of false positive or false negative results from the in vitro models. This article provides an overview of NSCLC, the different nanoparticles available to date, and in vitro evaluation of the nanoparticles. Different types of cells suitable for in vitro study and the important precautions to limit the development of false results are also extensively discussed.

Engineering PDA-coated CM-CS nanoparticles for photothermo-chemotherapy of osteosarcoma and bone regeneration

After an osteosarcoma excision, recurrence and bone defects are significant challenges for clinicians. Combination therapy based on a nanoparticle-based drug delivery system shows great promise in osteosarcoma therapy. In this study, we designed a multifunctional chitosan (CS) nanoparticle, which combined photothermal therapy (PTT) with chemotherapy to synergistically enhance osteosarcoma therapy and bone repair. Curcumin (CM) loaded CS nanoparticles were prepared through ionotropic gelation method and were further functionalized with polydopamine (PDA) coating to form CS-CM-PDA nanoparticles (CCPNPs). The CCPNPs displayed pH- and near-infrared (NIR)- responsive CM release behavior. In vitro anti-cancer results indicated that CCPNPs possessed a long-term stable anti-cancer effect compared to pure CM. The presence of the NIR irradiation combined with CCPNPs resulted in a dramatic decrease in MG-63 osteosarcoma cell viability in 10 min compared with the pure CCPNPs at the concentration of 500 μg/mL. Meanwhile, in vitro study demonstrated that CCPNPs induced MG-63 cell apoptosis via downregulating the expression of Bcl-2 and upregulating the expression levels of Bax and Caspase-3. Besides, CCPNPs could positively induce the proliferation of MC3T3-E1 osteoblast cells in vitro. These results suggested that CCPNPs with bifunctional osteosarcoma therapy and bone repair may be an excellent candidate for local cancer therapy and bone regeneration.

Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions.

Noise overexposure leads to hair cell loss, synaptic ribbon reduction, and auditory nerve deterioration, resulting in transient or permanent hearing loss depending on the exposure severity. Oxidative stress, inflammation, calcium overload, glutamate excitotoxicity, and energy metabolism disturbance are the main contributors to noise-induced hearing loss (NIHL) up to now. Gene variations are also identified as NIHL related. Glucocorticoid is the only approved medication for NIHL treatment. New pharmaceuticals targeting oxidative stress, inflammation, or noise-induced neuropathy are emerging, highlighted by the nanoparticle-based drug delivery system. Given the complexity of the pathogenesis behind NIHL, deeper and more comprehensive studies still need to be fulfilled.

Intra-articular Injection of Kartogenin-Enhanced Bone Marrow–Derived Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis in a Rat Model

Background: In this study, we investigated the in vitro and in vivo chondrogenic capacity of kartogenin (KGN)–enhanced bone marrow–derived mesenchymal stem cells (BMSCs) for cartilage regeneration. Purpose: To determine (1) whether functionalized nanographene oxide (NGO) can effectively deliver KGN into BMSCs and (2) whether KGN would enhance BMSCs during chondrogenesis in vitro and in vivo in an animal model. Study Design: Controlled laboratory study. Methods: Functionalized NGO with line chain amine-terminated polyethylene glycol (PEG) and branched polyethylenimine (BPEI) were used to synthesize biocompatible NGO-PEG-BPEI (PPG) and for loading hydrophobic KGN molecules noncovalently via π–π stacking and hydrophobic interactions (PPG-KGN). Then, PPG-KGN was used for the intracellular delivery of hydrophobic KGN by simple mixing and co-incubation with BMSCs to acquire KGN-enhanced BMSCs. The chondrogenic efficacy of KGN-enhanced BMSCs was evaluated in vitro. In vivo, osteoarthritis (OA) was induced by anterior cruciate ligament transection in rats. A total of 5 groups were established: normal (OA treated with nothing), phosphate-buffered saline (PBS; intra-articular injection of PBS), PPG-KGN (intra-articular injection of PPG-KGN), BMSCs (intra-articular injection of BMSCs), and BMSCs + PPG-KGN (intra-articular injection of PPG-KGN–preconditioned BMSCs). At 6 and 9 weeks after the surgical induction of OA, the rats received intra-articular injections of PPG-KGN, BMSCs, or KGN-enhanced BMSCs. At 14 weeks after the surgical induction of OA, radiographic and behavioral evaluations as well as histological analysis of the knee joints were performed. Results: The in vitro study showed that PPG could be rapidly uptaken in the first 4 hours after incubation, reaching saturation at 12 hours and accumulating in the lysosome and cytoplasm of BMSCs. Thus, PPG-KGN could enhance the efficiency of the intracellular delivery of KGN, which showed a remarkably high chondrogenic differentiation capacity of BMSCs. When applied to an OA model of cartilage injuries in rats, PPG-KGN–preconditioned BMSCs contributed to protection from joint space narrowing, pathological mineralization, OA development, and OA-induced pain, as well as improved tissue regeneration, as evidenced by radiographic, weightbearing, and histological findings. Conclusion: Our results demonstrate that KGN-enhanced BMSCs showed markedly improved capacities for chondrogenesis and articular cartilage repair. We believe that this work demonstrates that a multifunctional nanoparticle-based drug delivery system could be beneficial for stem cell therapy. Our results present an opportunity to reverse the symptoms and pathophysiology of OA. Clinical Relevance: The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.

A Deep Dive: SIWV Tetra-Peptide Enhancing the Penetration of Nanotherapeutics into the Glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor. It is difficult to regulate GBM using conventional chemotherapy-based methods due to its anatomical structure specificity, low drug targeting ability, and limited penetration depth capability to reach the tumor interior. Numerous approaches have been proposed to overcome such issues, including nanoparticle-based drug delivery system (DDS) with the development of GBM site targeting and penetration depth enhancing moieties (e.g., peptides, sugars, proteins, etc.). In this study, we prepared four different types of nanoparticles, which are based on porous silicon nanoparticles (pSiNPs) incorporating polyethylene glycol (PEG), iRGD peptide (well-known cancer targeting peptide), and SIWV tetra-peptide (a recently disclosed GBM-targeting peptide), and analyzed their deep-tumor penetration abilities in cell spheroids, in GBM patient-derived tumoroids, and in GBM xenograft mice. We found that SIWV tetra-peptide significantly enhanced the penetration depth of pSiNPs, and its therapeutic formulation (temozolomide-loaded/SIWV-functionalized pSiNPs) showed a higher anticancer efficacy compared with other formulations. These findings hold great promise for the development of nanotherapeutics and peptide-conjugated drugs for GBM.

A Smart Drug Delivery System Based on Thermo-Responsive Polymer Gated Au NRs@SiO2 Nano-Platform

A key challenge for nanoparticles-based drug delivery system is to achieve manageable drug release in tumour cell. In this study, a versatile system combining photothermal therapy and controllable drug release for tumour cells using temperature-sensitive block copolymer coupled Au NRs@SiO2 is reported. While the Au NRs serve as hyperthermal agent and the mesoporous silica was used to improve the drug loading and decrease biotoxicity. The block copolymer acted as “gatekeeper” to regulate the release of model drug (Doxorubicin hydrochloride, DOX). Through in vivo and in vitro experiments, we achieved the truly controllable drug release and photothermal therapy with the collaborative effect of the three constituents of the nanocomposites. The reported nanocomposites pave the way to high-performance controllable drug release and photothermal therapy system.

Glycyrrhetinic acid conjugated zein capped aminated mesoporous silica nanoparticle-based dual drug delivery system for liver: A pH-dependent triggered release

Nano-scale drug delivery systems have captivated the scientific community due to their controlled and targeted drug release. Nano carrier-based combination chemotherapy has improved pharmacokinetics of drugs compared to single drug administration. The objective of the present work is to develop a drug delivery system based on aminated mesoporous silica nanoparticles (AMSN) and zein, a plant protein for the co-delivery of 5-Fluorouracil (5-FU) and curcumin (CUR). The AMSN was obtained by the co-condensation method, which can accommodate CUR in its pores. Then the silica core was coated with glycyrrhetinic acid conjugated zein nanoparticle, which could act as a pH-responsive gatekeeper for AMSN as well as a carrier for 5-FU. The structure of the hybrid nanoparticle was characterized by FT-IR, XRD, SEM, TEM, DLS and TG analyses. The release studies were carried out at pH 7.4 and 5.5. The greater extent of drug release occurred at pH 5.5. About 78.00% of drug release happened within 120 h for 5-FU and 71.30% within 120 h for CUR. The in vitro release of drugs was analyzed using Peppas's empirical equation to understand the release mechanism. In vitro cell viability studies were conducted using MTT assay on HepG2 liver cancer cells and 3T3-L1 normal cells. At 1000 μg/mL, the drug carrier shows greater than 90.00% cell viability and AMSN-CUR/Z-GA-5-FU showed a higher toxicity of 68.80%. The results demonstrate that the prepared material is an efficient DDS for anticancer activity.

Dual-labeled visual tracer system for topical drug delivery by nanoparticle-triggered P-glycoprotein silencing

Using nanoparticle-based drug delivery systems as enhancers is a robust strategy for transdermal delivery; however, the mechanisms by which these systems promote transdermal penetration are still unclear. Here, we fabricated a dual-labeled nano drug delivery system that allows discrete visualization of both the drug and the nanoparticle carrier. To comprehensively examine its potential mechanism, we investigated its effects on human epidermal keratinocyte HaCaT cells, including changes in cell membrane potential, intracellular Ca2+ concentration, and Ca2+-ATPase activity. P-glycoprotein (P-gp) expression in nanoparticle-treated human dermal microvascular endothelial cells was detected by western blotting and immunofluorescence. Furthermore, the transdermal absorption and biodistribution of the dual-labeled nanoparticles were deeply investigated by skin permeability study in vitro and in vivo using fluorescence microscopy and in vivo imaging, respectively. In addition to reducing membrane potential, increasing the intracellular Ca2+ concentration, and decreasing Ca2+-ATPase activity, our results indicate that the dual-labeled nanoparticles can downregulate P-gp to promote transdermal absorption. Fluorescence and in vivo imaging visually demonstrated that the nanoparticle delivery system penetrated into the dermis through the stratum corneum. All these results indicate that this dual-labeled nano delivery system provides a new method for future in-depth visual explorations of transdermal drug delivery mechanisms.

A pH-responsive mesoporous silica nanoparticles-based drug delivery system with controlled release of andrographolide for OA treatment.

Andrographolide (AG) has favorable anti-inflammatory and antioxidative capacity. However, it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection, leading to low therapeutic efficiency in osteoarthritis (OA). Herein, we designed a nano-sized pH-responsive drug delivery system (DDS) for OA treatment by using modified mesoporous silica nanoparticles (MSNs) with pH-responsive polyacrylic acid (PAA) for loading of AG to form AG@MSNs-PAA nanoplatform. The nanoparticles have uniform size (∼120 nm), high drug loading efficiency (22.38 ± 0.71%) and pH-responsive properties, beneficial to sustained release in OA environment. Compared with AG, AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1β-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model, as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss. Therefore, the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.

A chitosan/mesoporous silica nanoparticle-based anticancer drug delivery system with a “tumor-triggered targeting” property

To enhance drug utilization and reduce their side effects, the strategy of “tumor-triggered targeting” was introduced to fabricate dual-pH-sensitive chitosan (CHI)/mesoporous silica nanoparticle (MSN)-based anticancer drug delivery system (DDS) in this work. Model drug doxorubicin hydrochloride (DOX) was loaded in MSN, which was modified with benzimidazole (Bz) group. Then chitosan-graft-β-cyclodextrin (CHI-g-CD) was applied as the “gatekeeper” to cover MSN through host-guest interaction between β-CD and Bz. After being coated with targeting peptide adamantane-glycine-arginine-glycine-aspartic acid-serine (Ad-GRGDS), methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) was finally grafted on CHI through the pH-sensitive benzoic imine bond. Due to the dynamic protection of PEG, the obtained carriers were “stealthy” at pH 7.4, but could reveal the shielded targeting peptide and the positive charge of CHI in the weakly acidic environment achieved a “tumor-triggered targeting”. Inside cancer cells, the interaction between β-CD and Bz group could be destroyed due to the lower pH, resulted in DOX release. Both in vitro and in vivo studies proved the DDS could targeting induce cancer cell apoptosis, inhibit tumor growth, and reduce the cytotoxicity of DOX against normal cells. It is expected that the system named DOX@MSN-CHI-RGD-PEG could be a potential choice for cancer therapy.