ABSTRACT
Liver cancer is one of the aggressive primary tumors as evident by high rate of incidence and mortality. Conventional treatments (e.g. chemotherapy) suffer from various drawbacks including wide drug distribution, low localized drug concentration, and severe off-site toxicity. Therefore, they cannot satisfy the mounting need for safe and efficient cancer therapeutics, and alternative novel strategies are needed. Nano-based drug delivery systems (NDDSs) are among these novel approaches that can improve the overall therapeutic outcomes. NDDSs are designed to encapsulate drug molecules and target them specifically to liver cancer. Thus, NDDSs can selectively deliver therapeutic agents to the tumor cells and avoid distribution to off-target sites which should improve the safety profile of the active agents. Nonetheless, NDDSs should be well designed, in terms of the preparing materials, nanocarriers structure, and the targeting strategy, in order to accomplish these objectives. This review discusses the latest advances of NDDSs for cancer therapy with emphasis on the aforementioned essential design components. The review also entails the challenges associated with the clinical translation of NDDSs, and the future perspectives towards next-generation NDDSs.
ABSTRACT
Drug resistance is a global health challenge with thousands of deaths annually caused by bacterial multidrug resistance (MDR). Efforts to develop new antibacterial molecules do not meet the mounting needs imposed by the evolution of MDR. An alternative approach to overcome this challenge is developing targeted formulations that can enhance the therapeutic efficiency and limit side effects. In this aspect, vancomycin is a potent antibacterial agent that has inherent bacterial targeting properties by binding to the D-Ala-D-Ala moiety of the bacterial peptidoglycan. However, the use of vancomycin is associated with serious side effects that limit its clinical use. Herein, we report the development of vancomycin-conjugated magnetic nanoparticles using a simple conjugation method for targeted antibacterial activity. The nanoparticles were synthesized using a multistep process that starts by coating the nanoparticles with a silica layer, followed by binding an amide linker and then binding the vancomycin glycopeptide. The developed vancomycin-conjugated magnetic nanoparticles were observed to exhibit a spherical morphology and a particle size of 16.3 ± 2.6 nm, with a silica coating thickness of 5 nm and a total coating thickness of 8 nm. The vancomycin conjugation efficiency on the nanoparticles was measured spectrophotometrically to be 25.1%. Additionally, the developed formulation retained the magnetic activity of the nanoparticles, where it showed a saturation magnetization value of 51 emu/g, compared to 60 emu/g for bare magnetic nanoparticles. The in vitro cell biocompatibility demonstrated improved safety where vancomycin-conjugated nanoparticles showed IC50 of 183.43 µg/mL, compared to a much lower value of 54.11 µg/mL for free vancomycin. While the antibacterial studies showed a comparable activity of the developed formulation, the minimum inhibitory concentration was 25 µg/mL, compared to 20 µg/mL for free vancomycin. Accordingly, the reported formulation can be used as a platform for the targeted and efficient delivery of other drugs.
ABSTRACT
Bacterial pneumonia is a common pulmonary infection responsible for premature death. Biomaterials based-carriers loaded with antibiotics enhance drug potency through localizing the therapy, minimizing the associated adverse effects, and improving patient compliance. Herein, this study reports the preparation of an inhalable dry powder formulation composed of a nano-in-microparticles. Vancomycin was adsorbed on the core of magnetic nanoparticles followed by spray drying into lactose/dextran to optimize the aerodynamic performance and allow the local delivery of the drug into the bacterial pneumonia infection site. Lactose and Dextran are polysaccharides commonly used for pulmonary delivery due to their optimum aerodynamic performance and biocompatibility. The preparation of the nano-in-micro particles with optimum properties was confirmed using FTIR, TEM, SEM, Laser-diffraction, ICP-AES and TGA. The TEM micrographs confirmed the formation of spherical magnetic nanoparticles with a diameter 14.7 ± 5.9 nm and a coating thickness 3 - 16 nm, while laser diffraction showed that outer microparticles exhibited a mean diameter < 5 µm. The formulations demonstrated a promising activity against S. aureus and MRSA and better biocompatibility using MTT assay. In vivo safety and pharmacokinetic studies confirmed the localization of VAN in lung tissue and minimized adverse effects compared to free VAN. Therefore, the developed nano-in-microparticles confers a good potential for eradication of lung infections.
Subject(s)
Magnetite Nanoparticles , Vancomycin , Humans , Lung , Staphylococcus aureusABSTRACT
PURPOSE: Conventional photosensitizers for photodynamic therapy (PDT) typically have wide tissue distribution and poor water solubility. A hyaluronic acid (HA) polymeric nanoparticle with specific lymphatic uptake and highly water solubility was developed to deliver pyropheophorbide-a (PPa) for locally advanced head and neck squamous cell carcinoma (HNSCC) treatment. METHODS AND RESULTS: PPa was chemically conjugated to the HA polymeric nanoparticle via an adipic acid dihydrazide (ADH) linker. The conjugates were injected subcutaneously in a region near the tumor. Near-infrared (NIR) imaging was used to monitor distribution, and diode laser was used to activate PPa. The singlet oxygen generation efficiency of PPa was not affected by conjugation to HA nanoparticles at a PPa loading degree of 1.89 w.t.%. HA-ADH-PPa inhibited human HNSCC MDA-1986 cell growth only when photo-irradiation was applied. After HA-ADH-PPa treatment and radiation, NU/NU mice bearing human HNSCC MDA-1986 tumors showed reduced tumor growth and significantly enhanced survival time compared with an untreated group (p < 0.05). CONCLUSIONS: These results demonstrate that HA-ADH-PPa could be useful for in vivo locoregional photodynamic therapy of HNSCC.
Subject(s)
Head and Neck Neoplasms , Nanoparticles , Photochemotherapy , Animals , Cell Line, Tumor , Head and Neck Neoplasms/drug therapy , Hyaluronic Acid/pharmacology , Mice , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Squamous Cell Carcinoma of Head and Neck/drug therapyABSTRACT
With the significant drawbacks of conventional cancer chemotherapeutics, cancer immunotherapy has demonstrated the ability to eradicate cancer cells and circumvent multidrug resistance (MDR) with fewer side effects than traditional cytotoxic therapies. Various immunotherapeutic agents have been investigated for that purpose including checkpoint inhibitors, cytokines, monoclonal antibodies and cancer vaccines. All these agents aid immune cells to recognize and engage tumor cells by acting on tumor-specific pathways, antigens or cellular targets. However, immunotherapeutics are still associated with some concerns such as off-target side effects and poor pharmacokinetics. Nanomedicine may resolve some limitations of current immunotherapeutics such as localizing delivery, controlling release and enhancing the pharmacokinetic profile. Herein, we discuss recent advances of immunotherapeutic agents with respect to their development and biological mechanisms of action, along with the advantages that nanomedicine strategies lend to immunotherapeutics by possibly improving therapeutic outcomes and minimizing side effects.
Subject(s)
Cancer Vaccines , Neoplasms , Biology , Humans , Immunotherapy , Nanomedicine , Neoplasms/therapyABSTRACT
Bacterial resistance is a real threat to human health. One of the most common strategies used to overcome this problem is the combination therapy. This study proposes a new chitosan-based nano-in-microparticles (NIMs) antibacterial platform that can deliver multiple antibacterial therapeutics at the same time. Chitosan (CS) was PEGylated to overcome its limited water solubility. Then, the antibacterial activity of the resulting PEG-CS was fortified via conjugation with dendritic polyamidoamine hyperbranches (HB) as well as in-situ immobilization of silver nanoparticles (AgNPs) to be efficient against multiple bacterial strains. Montmorillonite nanoclay (MMT) was prepared and used to encapsulate ibuprofen (IBU) as anti-inflammatory drug to reduce any concomitant inflammatory response during bacterial infection. The successful synthesis of PEG-HBCS-AgNPs as well as IBU-MMT nanocomplex was confirmed using FTIR, 1H NMR, DSC, TGA and EDX. SEM micrographs showed a complete formation of NIM spherical particles with a size around 13 µm. Besides, the newly developed drugs-loaded CS-based NIM formulation showed a better widespread activity on the tested aerobic and anaerobic bacterial species, and it may represent, after further optimization, a promising approach for overcoming multiple-bacterial infection.