Artesunate-Nanoliposome-TPP, a Novel Drug Delivery System That Targets the Mitochondria, Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Oxidative Stress and Inflammatory Effects.

Background: Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from Artemisia annua L. that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy. Methods: In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored. Results: T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1. Conclusion: T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI.

Emerging pharmacotherapies for the treatment of pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Approved treatment options currently primarily target abnormal cell signaling pathways involved in vasoconstriction and proliferation, such as those mediated by prostacyclin, cyclic guanosine monophosphate, and endothelin. AREAS COVERED: Recent advancements have led to new applications and modes of delivery of currently approved PAH medications. At the same time, novel drugs targeting specific molecular pathways involved in PAH pathogenesis have been developed and are being investigated in clinical trials. This review summarizes investigational drug trials for PAH gathered from a comprehensive search using PubMed and ClinicalTrials.gov between 2003 and 2023. It includes both currently approved medications studied at different doses or new administration forms and experimental drugs that have not yet been approved. EXPERT OPINION: Approved treatments for PAH target imbalances in pulmonary vasoactive pathways that work primarily on enhancing pulmonary vasodilation with less salient effects on pulmonary vascular remodeling. The advent of more locally acting inhaled medications offers additional therapeutic options that may improve the ease of drug delivery and reduce adverse systemic effects. The more recent emphasis on developing and applying therapeutics that directly impact the aberrant signaling pathways implicated in PAH appears more likely to advance the treatment of this devastating disease.

Gout therapeutics and drug delivery.

Gout is a common inflammatory arthritis caused by persistently elevated uric acid levels. With the improvement of people's living standards, the consumption of processed food and the widespread use of drugs that induce elevated uric acid, gout rates are increasing, seriously affecting the human quality of life, and becoming a burden to health systems worldwide. Since the pathological mechanism of gout has been elucidated, there are relatively effective drug treatments in clinical practice. However, due to (bio)pharmaceutical shortcomings of these drugs, such as poor chemical stability and limited ability to target the pathophysiological pathways, traditional drug treatment strategies show low efficacy and safety. In this scenario, drug delivery systems (DDS) design that overcome these drawbacks is urgently called for. In this review, we initially describe the pathological features, the therapeutic targets, and the drugs currently in clinical use and under investigation to treat gout. We also comprehensively summarize recent research efforts utilizing lipid, polymeric and inorganic carriers to develop advanced DDS for improved gout management and therapy.

Cell membrane nanomaterials composed of phospholipids and glycoproteins for drug delivery in inflammatory bowel disease: A review.

Inflammatory bowel disease (IBD) is a serious chronic intestinal disorder with an increasing global incidence. However, current treatment strategies, such as anti-inflammatory drugs and probiotics, have limitations in terms of safety, stability, and effectiveness. The emergence of targeted nanoparticles has revolutionized IBD treatment by enhancing the biological properties of drugs and promoting efficiency and safety. Unlike synthetic nanoparticles, cell membrane nanomaterials (CMNs) consist primarily of biological macromolecules, including phospholipids, proteins, and sugars. CMNs include red blood cell membranes, macrophage membranes, and leukocyte membranes, which possess abundant glycoprotein receptors and ligands on their surfaces, allowing for the formation of cell-to-cell connections with other biological macromolecules. Consequently, they exhibit superior cell affinity, evade immune responses, and target inflammation effectively, making them ideal material for targeted delivery of IBD therapies. This review explores various CMNs delivery systems for IBD treatment. However, due to the complexity and harsh nature of the intestinal microenvironment, the lack of flexibility or loss of selectivity poses challenges in designing single CMNs delivery strategies. Therefore, we propose a hierarchically programmed delivery modality that combines CMNs with pH, charge, ROS and ligand-modified responsive nanoparticles. This approach significantly improves delivery efficiency and points the way for future research in this area.

Intrathecal Drug Delivery Systems for Cancer Pain Control: Insights on Current Contemporary Practices in the US.

OBJECTIVES: Among patients with cancer with moderate to severe, intractable pain, intrathecal drug delivery using an intrathecal drug delivery system (IDDS) offers effective pain control. In this study, we evaluate the trends of IDDS therapy among patients with cancer, associated comorbidities, complications, and outcomes, using a large representative US administrative inpatient data base. MATERIALS AND METHODS: The Nationwide Inpatient Sample (NIS) data base contains data from 48 states and the District of Columbia. The NIS was used to identify patients with cancer who underwent IDDS implantation between 2016 and 2019. Patients with cancer with intrathecal pumps for the treatment of chronic pain were identified using administrative codes. Baseline demographics, hospital characteristics, type of cancer associated with IDDS implantation, palliative care encounters, hospitalization costs, length of stay, and prevalence of bone pain were evaluated in the study. RESULTS: A total of 22,895 (0.32%) individuals with hospital admission for IDDS surgery were included for analysis among 7.06 million individuals with cancer in the final cohort. The IDDS cohort consisted of patients predominantly in the 65-to-79 years age group (40.49%), female sex (50.42%), and Caucasian ethnicity (75.82%). The top five cancers in patients receiving IDDS were lung (27.15%), colorectal (24.9%), liver (16.44%), bone (8.01%), and liver (7.99%) cancer. In addition, the length of stay was six days (interquartile range [IQR] four-nine days) and the median cost of hospital admission was $29,062 (IQR $19,413-$42,261) in the patients who received an IDDS. These factors were greater than those in patients without IDDS. CONCLUSIONS: A very few patients with cancer received IDDS in the US during the study period. Despite recommendations supporting its use, there are significant racial and socioeconomic disparities in IDDS use.

Advances in antibody-based drugs and their delivery through the blood-brain barrier for targeted therapy and immunotherapy of gliomas.

Gliomas are highly invasive and are the most common type of primary malignant brain tumor. The routine treatments for glioma include surgical resection, radiotherapy, and chemotherapy. However, glioma recurrence and patient survival remain unsatisfactory after employing these traditional treatment approaches. With the rapid development of molecular immunology, significant breakthroughs have been made in targeted glioma therapy and immunotherapy. Antibody-based therapy has excellent advantages in treating gliomas due to its high specificity and sensitivity. This article reviewed various targeted antibody drugs for gliomas, including anti-glioma surface marker antibodies, anti-angiogenesis antibodies, and anti-immunosuppressive signal antibodies. Notably, many antibodies have been validated clinically, such as bevacizumab, cetuximab, panitumumab, and anti-PD-1 antibodies. These antibodies can improve the targeting of glioma therapy, enhance anti-tumor immunity, reduce the proliferation and invasion of glioma, and thus prolong the survival time of patients. However, the existence of the blood-brain barrier (BBB) has caused significant difficulties in drug delivery for gliomas. Therefore, this paper also summarized drug delivery methods through the BBB, including receptor-mediated transportation, nano-based carriers, and some physical and chemical methods for drug delivery. With these exciting advancements, more antibody-based therapies will likely enter clinical practice and allow more successful control of malignant gliomas.

Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration.

PURPOSE: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-µg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). DESIGN: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON). PARTICIPANTS: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm2 and ≤ 18 mm2 in the study eye. METHODS: Enrolled patients were randomized to treatment with intravitreal injections of 400-µg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21. MAIN OUTCOME MEASURES: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24. RESULTS: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm2/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm2 with Brimo DDS (n = 84) versus 3.48 (0.13) mm2 with sham (n = 91), a reduction of 0.25 mm2 (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm2 with Brimo DDS (n = 49) versus 4.52 (0.15) mm2 with sham (n = 46), a reduction of 0.43 mm2 (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed. CONCLUSIONS: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

Nanoparticles for cancer therapy: a review of influencing factors and evaluation methods for biosafety.

Nanoparticles are widely used in the biomedical field for diagnostic and therapeutic purposes due to their small size, high carrier capacity, and ease of modification, which enable selective targeting and as contrast agents. Over the past decades, more and more nanoparticles have received regulatory approval to enter the clinic, more nanoparticles have shown potential for clinical translation, and humans have increasing access to them. However, nanoparticles have a high potential to cause unpredictable adverse effects on human organs, tissues, and cells due to their unique physicochemical properties and interactions with DNA, lipids, cells, tissues, proteins, and biological fluids. Currently, issues, such as nanoparticle side effects and toxicity, remain controversial, and these pitfalls must be fully considered prior to their application to body systems. Therefore, it is particularly urgent and important to assess the safety of nanoparticles acting in living organisms. In this paper, we review the important factors influencing the biosafety of nanoparticles in terms of their properties, and introduce common methods to summarize the biosafety evaluation of nanoparticles through in vitro and in body systems.

Loss of effectiveness with an implanted drug delivery system for intrathecal pain therapy due to corrosion.

INTRODUCTION: Intrathecal drug delivery is an established invasive treatment option. Most common complication is catheter malfunction, which can lead to overdose or withdrawal. CASE PRESENTATION: A 61-year-old female patient underwent an elective replacement of an intrathecal drug delivery pump. The patient complained about a loss of effectiveness over the past 2 years. Intraoperatively, a white mass corresponding to morphine precipitation in the pump pocket was found, which appeared to be due to corrosion at the pump-catheter connection site. CONCLUSIONS: Recommendations on how to deal with the decreasing effectiveness of intrathecal drug delivery and on intraoperative catheter handling are provided.

Insight into the pivotal role of signaling pathways in psoriasis pathogenesis, potential therapeutic molecules and drug delivery approaches.

Psoriasis is a multifactorial chronic autoimmune skin disorder, the exact cause of which is still under investigation. It is classified into different types displaying various histopathological features such as hyperproliferation, irregular parakeratosis and vascular infiltration of various immune cells with neutrophils in the epidermis. Over the past few decades, psoriasis pathogenesis has been thoroughly researched, leading to several advances in the treatment using small molecules and biologics. This review focuses on describing the role of various signaling pathways, including PDE-4, JAK-STAT, S1P, A3AR and NF-κB, in psoriasis pathogenesis and associated new molecules that are either recently approved or under clinical trials. This study has also addressed the relevance of employing nanotherapeutics to boost the efficacy of psoriasis treatment.

Effectiveness and Safety of Intrathecal Drug Delivery Systems for the Management of Cancer Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: Intrathecal drug delivery systems (IDDS) and spinal cord stimulation (SCS) have been proposed and assessed for the management of cancer pain; however, such treatments remain underused. We conducted a systematic review to evaluate the effectiveness and safety of IDDS and SCS for cancer pain. MATERIALS AND METHODS: Electronic databases MEDLINE, CENTRAL, EMBASE, and WikiStim were searched from 1988 to March 2021. Randomized controlled trials and observational studies of adults with pain related to cancer or its treatment who received an implantable IDDS or SCS were eligible for inclusion. The primary outcome of the review was change in pain intensity from baseline to the last available follow-up, measured using a visual analog scale or numerical rating scale. The protocol for this review is registered on PROSPERO (CRD42021240717). RESULTS: A total of 22 studies (24 reports) included a total of 3043 participants who received either IDDS or SCS for cancer pain. Eight studies reporting data for 405 participants with an IDDS could be included in the meta-analysis of pain intensity that showed a statistically significant reduction at the latest posttreatment follow-up time compared with baseline (mean difference [MD], -3.31; 95% CI, -4.18 to -2.45; p < 0.001). Six studies reporting data for 325 participants with an IDDS could be included in the meta-analysis of pain intensity that showed a statistically significant reduction up to one month after treatment compared with baseline (MD, -3.53; 95% CI, -4.06 to -3.00; p < 0.001). A meta-analysis including studies of participants with either an IDDS or an SCS device showed similar results. Improvements in other outcomes following implantation of IDDS also were observed. Postdural puncture headache was the most reported complication, whereas urinary retention, nausea, and vomiting were commonly reported side effects. CONCLUSION: Our findings suggest that IDDS is effective in reducing pain intensity for patients with cancer pain when compared with pretreatment.

Effects of an Intrathecal Drug Delivery System Connected to a Subcutaneous Port on Pain, Mood and Quality of Life in End Stage Cancer Patients: An Observational Study.

BACKGROUND: In cancer patients with limited life expectancy, an implant of an intrathecal (IT) drug delivery system connected to a subcutaneous port (IDDS-SP) has been proposed as a successful strategy, but conflicting results are reported on quality of life (QoL). The aim of this prospective observational study is to report the effects on pain, mood and QoL of an IT combination therapy delivered by an IDDS-SP in malignant refractory pain. METHODS: Adult patients in which IT therapy was recommended were recruited. An IT therapy with morphine and levobupivacaine was started: VASPI score, depression and anxiety (evaluated by the Edmonton Symptom Assessment System -ESAS-), the Pittsburgh Sleep Quality Index (PSQI), the 5-level EuroQol 5D version (EQ-5D-5L) and the requirements of breakthrough cancer pain (BTcP) medications were registered, with adverse events rate and the satisfaction of patients scored as Patient Global Impression of Change (PGIC). RESULTS: Fifty patients, (16 F/34 M) were enrolled (age 69 ± 12). All had advanced cancer with metastasis. The median daily VASPI score was 75, the median depression score was 6, and the median anxiety score was 4, median PSQI was 16. At 28 days, a significant reduction in VASPI score was registered as well as in depression and anxiety item. Also, PSQI decreased significantly. The EQ-5D-5 L showed a significant improvement in all components at 14 and 28 days. Patient Global Impression of Change scores showed high level of satisfaction. A low incidence of adverse events and a reduction in BTCP episodes were also registered. CONCLUSION: Intrathecal combination therapy delivered by an IDDS-SP could ensure adequate control of cancer related symptoms, such as pain, depression, anxiety and sleep disturbances. These effects, with low rate of AEs and reduced BTcP episodes, could explain the improvement in QoL and the overall high levels of patients' satisfaction.

Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab.

PURPOSE: To provide strategies for the management of key ocular adverse events (AEs) that may be encountered with the Port Delivery System with ranibizumab (PDS) in practice and provide recommendations that may mitigate such AEs based on clinical trial experiences and considerations from experts in the field. DESIGN: Safety evaluation based on the phase 2 Ladder (NCT02510794) and phase 3 Archway (NCT03677934) trials of the PDS. METHODS: The PDS implant is a permanent, indwelling, and refillable ocular drug delivery system that requires standardized procedural steps for its insertion and refill-exchange procedures, which evolved during the PDS clinical program. We described identified AEs that may arise after implant insertion or refill-exchange procedures, including conjunctival retraction, conjunctival erosion, endophthalmitis, implant dislocation, conjunctival blebs or conjunctival filtering bleb leaks, wound leaks, hypotony, choroidal detachment, vitreous hemorrhage, rhegmatogenous retinal detachment, cataract, and septum dislodgement. RESULTS: Adverse events related to the PDS were well understood, were manageable by trial investigators, and did not prevent patients from achieving optimal outcomes in most cases. CONCLUSIONS: Surgeons using the PDS should be aware of potential ocular AEs and identify them early for optimal management. As with any new surgical procedure, it is important to provide surgeons with appropriate training, ensure adherence to optimal surgical techniques, and continually refine the procedure to mitigate complications and improve outcomes.

Toxicological Aspects of Iron Oxide Nanoparticles.

Iron oxide nanoparticles (ION), with unique magnetic properties, have attracted huge scientific attention for a wide variety of uses, mostly in the biomedical field, due to their high biocompatibility, ability to cross biological membranes, appropriate surface architecture and easy conjugation with targeting ligands. Their current applications include diagnostic imaging, cell labelling, site-directed drug delivery and anticancer hyperthermia therapy. The ION surface may be modified by coating with different materials, aiming to stabilize the nanoparticles in different environments, to allow biomolecule binding favouring surface attachments with several molecules, and to prolong the recognition time by the immune system. Although the potential benefits of ION are considerable, and more and more ION are being manufactured to meet the demands of the rapidly proliferating field of nanomedicine, there is an urgent need to define their toxicological profile in order to avoid any potential health risks associated with their exposure and to reach optimal benefits of their use. The purpose of this chapter is to de-scribe the current knowledge on the ION toxicological features, addressing their structure and physicochemical characteristics, main exposure pathways and toxicokinetic aspects, interaction with cells, and their toxic effects, with special attention to those at the cellular and molecular level.

Renal Nano-drug delivery for acute kidney Injury: Current status and future perspectives.

Acute kidney injury (AKI) causes considerable morbidity and mortality, particularly in the case of post-cardiac infarction or kidney transplantation; however, the site-specific accumulation of small molecule reno-protective agents for AKI has often proved ineffective due to dynamic fluid and solute excretion and non-selectivity, which impedes therapeutic efficacy. This article reviews the current status and future trajectories of renal nanomedicine research for AKI management from pharmacological and clinical perspectives, with a particular focus on appraising nanosized drug carrier (NDC) use for the delivery of reno-protective agents of different pharmacological classes and the effectiveness of NDCs in improving renal tissue targeting selectivity and efficacy of said agents. This review reveals the critical shift in the role of the small molecule reno-protective agents in AKI pharmacotherapy - from prophylaxis to treatment - when using NDCs for delivery to the kidney. We also highlight the need to identify the accumulation sites of NDCs carrying reno-protective agents in renal tissues during in vivo assessments and detail the less-explored pharmacological classes of reno-protective agents whose efficacies may be improved via NDC-based delivery. We conclude the paper by outlining the challenges and future perspectives of NDC-based reno-protective agent delivery for better clinical management of AKI.

Jet injectors: Perspectives for small volume delivery with lasers.

Needle-free jet injectors have been proposed as an alternative to injections with hypodermic needles. Currently, a handful of commercial needle-free jet injectors already exist. However, these injectors are designed for specific injections, typically limited to large injection volumes into the deeper layers beneath the skin. There is growing evidence of advantages when delivering small volumes into the superficial skin layers, namely the epidermis and dermis. Injections such as vaccines and insulin would benefit from delivery into these superficial layers. Furthermore, the same technology for small volume needle-free injections can serve (medical) tattooing as well as other personalized medicine treatments. The research dedicated to needle-free jet injectors actuated by laser energy has increased in the last decade. In this case, the absorption of the optical energy by the liquid results in an explosively growing bubble. This bubble displaces the rest of the liquid, resulting in a fast microfluidic jet which can penetrate the skin. This technique allows for precise control over volumes (pL to µL) and penetration depths (µm to mm). Furthermore, these injections can be tuned without changing the device, by varying parameters such as laser power, beam diameter and filling level of the liquid container. Despite the published research on the working principles and capabilities of individual laser-actuated jet injectors, a thorough overview encompassing all of them is lacking. In this perspective, we will discuss the current status of laser-based jet injectors and contrast their advantages and limitations, as well as their potential and challenges.

New advances in brain-targeting nano-drug delivery systems for Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and its incidence is increasing due to the ageing population. Currently, the main limitations of AD treatment are low blood-brain barrier permeability, severe off-target of drugs, and immune abnormality. In this review, four hypotheses for Alzheimer's pathogenesis and three challenges for Alzheimer's drug delivery are discussed. In addition, this article summarises the different strategies of brain targeting nano-drug delivery systems (NDDSs) developed in the last 10 years. These strategies include receptor-mediated (transferrin receptor, low-density lipoprotein receptor-related protein, lactoferrin receptor, etc.), adsorption-mediated (cationic, alkaline polypeptide, cell-penetrating peptides, etc.), and transporter-mediated (P-gp, GLUT1, etc.). Moreover, it provides insights into novel strategies used in AD, such as exosomes, virus-like particles, and cell membrane coating particles. Hence, this review will help researchers to understand the current progress in the field of NDDSs for the central nervous system and find new directions for AD therapy.HighlightsCharacteristics and challenges based on the pathogenesis of AD were discussed.Recent advances in novel brain-targeting NDDSs for AD over the past 10 years were summarised.

Nanobubbles: A Novel Targeted Drug Delivery System

Abstract Nanobubbles are nanometer size bubbles having different constituents of varying physicochemical characteristic for the inner core and outer shell. Nanobubbles are mainly fabricated to improve the stability, bioavailability and improve the biodistribution of the delivered drug to the specific targeted site. Their small sizes bubbles allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Nanobubbles are developing as important contrast agents for imaging and carriers for drug delivery at targeted region. Sonication is the primary method for preparation of nanobubbles followed by thin-layer evaporation, high shear emulsification, mechanical agitation and coacervation or coalescence. With exposure to ultrasound/extracorporeal shock waves, the drug is liberated from the nanobubbles into the target cells. This review paper is an effort to reveal the different formulation development techniques briefly and varying shell and core content for developing nanobubbles.

Research progress in strategies to improve the efficacy and safety of doxorubicin for cancer chemotherapy.

INTRODUCTION: DOX exerts strong anticancer activity and is commonly used to treat different cancers, including bone sarcomas, soft tissues, bladder, ovary, stomach, thyroid, breast, acute lymphoblastic leukemia, Hodgkin lymphoma, lung cancer, and myeloblastic leukemia. However, the cumulative doses of DOX above 550mg/m2 cause irreversible cardiotoxicity and other severe adverse effects. In this context, concerning DOX, several patents have been published in the last two decades. This activity highlights various aspects of DOX, such as registered patent analysis, pharmacological action, toxicityminimization, formulation development such as those approved by FDA, under clinical trials, and newly developed nano-delivery systems. AREAS COVERED: This review analyzes the different aspects of DOX-based chemotherapeutics and the development of drug delivery systems in theliterature published from 2000 to early 2020. EXPERT OPINION: DOX-based chemotherapy is still few steps away from being "perfect and safe" therapy. Certain severe systemic side effects are associated with DOX therapy. It is expected that, in the near future, DOX therapy can be much effective by selecting an ideal nanocarrier system, DOX conjugates, proper structural modifications, DOX-immunotherapy, and combination therapy. The advanced formulationsof DOX from the registered patents and recent research articles need clinical trials to bring safe treatment for cancer patients.

Evaluation of the environmental contamination and exposure risk in medical/non-medical staff after oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a technique to directly deliver chemotherapeutic drugs in the abdomen for the treatment of peritoneal metastases. Pressurization improves the treatment efficacy but increases the risk of exposure for the medical/non-medical staff who can be exposed by dermal or ocular contact, or inhalation of aerosols containing the cytotoxic drugs. The aim of this study was to evaluate the risk of exposure for the medical/non-medical staff (nurses, surgeons, anaesthesiologists and cleaning personnel; n = 13) during PIPAC with oxaliplatin performed according to the protocol recommended in France. Blood samples were collected 1 h before and immediately after PIPAC, and urine samples 1 h before, and then 3 h and the morning after PIPAC. In the control, non-exposed group (n = 7), only one urine and blood sample were collected. Surface contamination in the operating room was assessed in water- and Surfanios-impregnated wipe samples. The total elemental platinum in each sample was quantified by inductively coupled plasma mass spectrometry, using a method adapted to quantify trace amounts (ng.L-1) in very low volumes (100 µl). No surface contamination was detected. Although 25% of urine samples in the exposed group contained platinum, no statistical difference was observed in urine and plasma samples collected before and after PIPAC and with the control group samples. These findings suggest that the French PIPAC protocol does not increase the risk of exposure to platinum in all staff categories involved. This protocol could be considered in future occupational policies and consensus statements. Trial registration: NCT04014426.