Macrophage membrane coated nanoparticles: a biomimetic approach for enhanced and targeted delivery

The enhanced and targeted drug delivery with low systemic toxicity and subsequent release of drugs is the major concern among researchers and pharmaceutics. Inspite of greater advancement and discoveries in...

Systemic toxicity in a child after topical cyclopentolate eye drops application

An 8-year-old girl was seen in our ophthalmology OPD who had come with complaints of mild pain in both eyes for 1 month. Her unaided vision in both eyes was 6/6. Her weight was 20 kg. Cyclopentolate 1% eye drops was administered twice to the child at 5 min interval in both eyes. The child became restless after 30 min of installation of eye drops installation. She started behaving abnormally and was not allowing to do retinoscopic examination. She had altered behavior, visual hallucination, and difficulty in walking. She was disoriented with slurred speech. She had ataxia and frequent tightening of limbs with jerky movements and was plucking her hair. Her pulse rate was 90/min and blood pressure was 120/90 mm of Hg. Her oxygen saturation was 94% in room air. The child was shifted to nearby hospital where a paediatrician and anesthesiologist were available and was kept under observation. Child’s pulse, blood pressure, and oxygen saturation were monitored for the next 5 hours. The child recovered completely over the next 8 hours.

Adverse reactions of local anesthetics

The article explains the adverse reactions of local anesthetics, in particular one of them, called the toxicity of local anesthetics. It has been shown that for the development of systemic toxicity of local anesthetics, higher doses of the latter are required in comparison with those recommended in the instructions. It is proposed in the regulatory documents to replace the term 'toxicity of local anesthetics' with the term 'side effects of local anesthetics'

Systemic toxicity of metal ions release from specific types of implanted medical devices: Systemic review of clinical studies

There is public concern over the long term systemic health effects of metal released from implanted medical devices that use metal alloys. Systemic toxic side effects have been associated with excessive metal ion release from implants into human biological specimen's circulation, in which cobalt and chromium plays an important role. Cobalt intoxication has become more frequent due to the wide use of metallic medical implants. Despite the technological improvements in replacement metallic medical implants, wear and corrosion products associated with the metal compounds of these implants may result in systemic reactions and toxicities. The current review encompasses a literature of the systemic toxicity studies concerning the effect of metallic wear debris released from wear and corrosion of specific types of implanted medical devices, resulting in a postoperative increase in metal ion levels in bodily fluids and at different organ sites. Release of metallic debris is mainly in the form of particles and ions of different valences, and oxides composed of cobalt and chromium. Toxicological, clinically significant, data regarding "potential hazards" of circulating metals after systemic chronic exposure to the metal ions from metals have been included. This review further highlights some of the clinical features of cobalt toxicity.

Antineoplastics Encapsulated in Nanostructured Lipid Carriers

Ideally, antineoplastic treatment aims to selectively eradicate cancer cells without causing systemic toxicity. A great number of antineoplastic agents (AAs) are available nowadays, with well-defined therapeutic protocols. The poor bioavailability, non-selective action, high systemic toxicity, and lack of effectiveness of most AAs have stimulated the search for novel chemotherapy protocols, including technological approaches that provide drug delivery systems (DDS) for gold standard medicines. Nanostructured lipid carriers (NLC) are DDS that contain a core of solid and lipid liquids stabilised by surfactants. NLC have high upload capacity for lipophilic drugs, such as the majority of AAs. These nanoparticles can be prepared with a diversity of biocompatible (synthetic or natural) lipid blends, administered by different routes and functionalised for targeting purposes. This review focused on the research carried out from 2000 to now, regarding NLC formulations for AAs (antimetabolites, antimitotics, alkylating agents, and antibiotics) encapsulation, with special emphasis on studies carried out in vivo. NLC systems for codelivery of AAs were also considered, as well as those for non-classical drugs and therapies (natural products and photosensitisers). NLC have emerged as powerful DDS to improve the bioavailability, targeting and efficacy of antineoplastics, while decreasing their toxic effect in the treatment of different types of cancer.

Construction of a Multifunctional Nano-Scale Metal-Organic Framework-Based Drug Delivery System for Targeted Cancer Therapy

The antitumor activity of triptolide (TP) has received widespread attention, although its toxicity severely limits its clinical application. Therefore, the design of a targeted drug delivery system (TDDS) has important application prospects in tumor treatment. Metal–organic frameworks (MOFs), with high drug-carrying capacity and good biocompatibility, have aroused widespread interest for drug delivery systems. Herein, folic acid (FA) and 5-carboxylic acid fluorescein (5-FAM) were used to modify Fe-MIL-101 to construct a functionalized nano-platform (5-FAM/FA/TP@Fe-MIL-101) for the targeted delivery of the anti-tumor drug triptolide and realize in vivo fluorescence imaging. Compared with Fe-MIL-101, functionalized nanoparticles not only showed better targeted therapy efficiency, but also reduced the systemic toxicity of triptolide. In addition, the modification of 5-FAM facilitated fluorescence imaging of the tumor site and realized the construction of an integrated nano-platform for fluorescence imaging and treatment. Both in vitro and in vivo studies of functionalized nanoparticles have demonstrated excellent fluorescence imaging and synergistic targeting anticancer activity with negligible systemic toxicity. The development of functional nano-platform provides new ideas for the design of MOF-based multifunctional nano-drug delivery system, which can be used for precise treatment of tumor.

Two-Step Targeted Drug Delivery Via Proteinaceous Barnase-Barstar Interface and PLGA-Based Nano-Carrier

The conventional methods of treating cancer with chemo- and radiotherapy present plenty of serious problems, such as low therapeutic index and high systemic toxicity. The advanced cancer treatment strategies utilize nanoformulations of drugs that can enter a tumor due to the enhanced permeability and retention (EPR) effect. However, EPR fails in the treatment of several human diseases. Mainstream biomedical studies are focused on creating the drugs that would enter the tumor with higher effectiveness and require smaller doses for administration. A two-stage drug delivery system is an encouraging alternative solution. At first, the primary, non-toxic targeting module is delivered to the tumor cells, followed by injection of the second complementary targeting module at a considerably lower dose, thus decreasing systemic toxicity. To meet the challenge, we have developed a two-stage drug delivery system (DDS), mediated by the high-affinity binding of the Barnase*Barstar protein pair. Barnase and Barstar act as lego bricks linking the first and the second modules on the surface of the cancer cell. Barnase (12 kDa) is a natural ribonuclease from Bacillus amyloliquefaciens, while Barstar (10 kDa) is its natural inhibitor. The Barnase*Barstar is one of the strongest known protein*protein complexes with Kaff = 1014 M−1 exhibiting extraordinarily stability in severe conditions. Artificial scaffold polypeptide DARPin9_29 genetically fused with Barstar served is a first module of the developed two-step DDS. DARPin9_29 (14 kDa) specifically recognizes the tumor marker HER2 overexpressed on human breast cancer cells. As a second module, a therapeutic nano-cargo was developed based on fluorescent polymer PLGA nanoparticles loaded with diagnostic Nile Blue dye and the chemotherapeutic drug doxorubicin. This nano-PLGA structure was covalently coupled to Barnase. We showed two-stage efficient labeling of HER2-overexpressing cancer cells using the first non-toxic module DARPin9_29-Barstar and the second toxic nano-module PLGA-Barnase. We demonstrated the doxorubicin-induced cytotoxicity of this two-step DDS based on polymer nanoparticles and proteinaceous Barnase-Barstar interface and showed more than 10-fold therapeutic dose reduction versus free doxorubicin. We believe that the developed two-step DDS based on PLGA nano-cargo and protein interface will promote the creation of new-generation cancer treatment strategies.