Lipid emulsion treatment for local anesthetic systemic toxicity in pediatric patients: A systematic review.

BACKGROUND: Local anesthetic systemic toxicity (LAST) is rare, but fatal; the current widely used treatment is lipid emulsion (LE). The goal of this study was to analyze and review case reports on LE treatment for LAST in pediatric patients. METHODS: We performed a systematic review using case reports on LE treatment for LAST in pediatric patients, searching PubMed and Scopus databases to March 2023 using the following keywords: ("local anesthetic toxicity" OR "local anesthetic systemic toxicity" OR LAST") AND ("newborn" OR "infant" OR "child" OR "children" OR "adolescent" OR "pediatric") AND ("lipid emulsion" OR "Intralipid"). RESULTS: Our search yielded 21 cases, revealing that nearly 43% patients with LAST were less than 1 year old, and most cases were caused by bupivacaine (approximately 67% cases). "Inadvertent intravascular injection" by anesthesiologists and "overdose of local anesthetics" mainly by surgeons were responsible for 52% and 24% cases of LAST, respectively. LAST occurred in the awake state (52%) and under general anesthesia (48%), mainly causing seizures and arrhythmia, respectively. Approximately 55% of patients received LE treatment in <10 minutes after LAST, mainly improving cardiovascular symptoms. A 20% LE (1.5 mL/kg) dose followed by 0.25 mL/kg/minutes dose was frequently used. LE and anticonvulsants were mainly used in the awake state, whereas LE with or without vasopressors was mainly used under general anesthesia. LE treatment led to full recovery from LAST in 20 cases; however, 1 patient died due to underlying disease. CONCLUSION: Consequently, our findings reveal that LE is effective in treating pediatric LAST.

Intrapleural injection of brucea javanica oil emulsion provided a long-term benefits in patient with malignant pleural effusion from pleural mesothelioma: A case report.

Malignant pleural mesothelioma (MPM) is a severe form of cancer that originates from mesothelium cells. Around 54-90% of mesotheliomas are associated with pleural effusions. Brucea Javanica Oil Emulsion (BJOE) is the processed oil derived from the seeds of Brucea javanica, which has shown potential as a treatment option for several types of cancer. Here, we present a case study of a MPM patient with malignant pleural effusion who received intrapleural injection of BJOE. The treatment resulted in the complete response of pleural effusion and chest tightness. While the precise mechanisms underlying the therapeutic effects of BJOE for pleural effusion are not yet fully understood, it has demonstrated a satisfactory clinical response without significant adverse effects.

Genicular artery embolization for knee osteoarthritis: Results of the LipioJoint-1 trial.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of transient genicular artery embolization (GAE) using an ethiodized oil-based emulsion for the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: This prospective, single-arm, open-label, multicenter, first-in-human cohort trial was registered on ClinicalTrials.gov (NCT04733092). The main inclusion criterion was diagnosis of KOA according to a visual analogue scale (VAS) pain score ≥ 40 mm (score range: 0-100 mm), despite conservative treatment for at least three months. Treatment efficacy was assessed using changes in VAS pain score, Mean Western Ontario & McMaster Universities osteoarthritis (WOMAC) function score (normalized to 100; score ranging from 0 to100) and outcome measures in rheumatoid arthritis clinical trials (OMERACT)-Osteoarthritis Research Society (OARSI) set of responder criteria. RESULTS: Twenty-two consecutive participants (13 women; mean age, 66 ± 9 [standard deviation (SD)]) were included and underwent GAE. Emulsion consisted in a mixture of ioversol and ethiodized oil (ratio 1:3, respectively) prepared extemporaneously. The rate of serious adverse events attributed to GAE within one month was 5% (1/22), corresponding to reversible worsening of renal function. Immediate technical success rate was 100%. Mean VAS pain score dropped from 74.4 ± 16.5 (SD) mm at baseline to 37.2 ± 26.7 (SD) mm at three months (P < 0.001). Mean WOMAC function score (normalized to 100: score ranging from 0 to 100) decreased from 57.3 ± 17.1 (SD) at baseline to 33.5 ± 25.9 (SD) at three months (P < 0.001). At three months, 16 out of 22 participants (73%) were considered responders according to the OMERACT-OARSI set of responder criteria, including high improvement in either pain or WOMAC function, or improvement in both pain and WOMAC function. CONCLUSION: GAE using an ethiodized oil-based emulsion is safe and improves pain and function in participants with KOA for at least three months.

A Bioactive Compound-Loaded Zinc-Aminoclay Encapsulated, Pickering Emulsion System for Treating Acne-Inducing Microbes.

Acne is a common skin condition caused by the growth of certain bacteria. Many plant extracts have been investigated for their potential to combat acne-inducing microbes, and one such plant extract is microwave-assisted Opuntia humifusa extract (MA-OHE). The MA-OHE was loaded onto zinc-aminoclay (ZnAC) and encapsulated in a Pickering emulsion system (MA-OHE/ZnAC PE) to evaluate its therapeutic potential against acne-inducing microbes. Dynamic light scattering and scanning electron microscopy were used to characterize MA-OHE/ZnAC PE with a mean particle diameter of 353.97 nm and a PDI of 0.629. The antimicrobial effect of MA-OHE/ZnAC was evaluated against Staphylococcus aureus (S. aureus) and Cutibacterium acnes (C. acnes), which contribute to acne inflammation. The antibacterial activity of MA-OHE/ZnAC was 0.1 and 0.025 mg/mL to S. aureus and C. acnes, respectively, which were close to naturally derived antibiotics. Additionally, the cytotoxicity of MA-OHE, ZnAC, and MA-OHE/ZnAC was tested, and the results showed that they had no cytotoxic effects on cultured human keratinocytes in a range of 10-100 µg/mL. Thus, MA-OHE/ZnAC is suggested to be a promising antimicrobial agent for treating acne-inducing microbes, while MA-OHE/ZnAC PE is a potentially advantageous dermal delivery system.

Network meta-analysis of 8 types of traditional Chinese medicine injection combined with chemotherapy in colorectal cancer treatment.

OBJECTIVE: This study conducted a network meta-analysis to comprehensively compare the efficacy and safety of 8 types of traditional Chinese medicine injection combined with chemotherapy in colorectal cancer treatment. METHODS: We searched relevant previous studies from databases including Pubmed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Service System (SinMed), VIP, and Wanfang Database. The searched studies spanned from the inception of databases to December 2022. The included randomized controlled trials were screened; data were extracted; and bias risk was assessed. The network meta-analysis was performed using Revman 5.4 software, R software, and STATA software. RESULTS: Fifty randomized controlled studies were included, including 8 types of traditional Chinese medicine injection. The results showed that Aidi injection [OR 1.65,95%CI (1.33,2.05)], compound Kushenshen injection [OR 2.72,95%CI (2.12,3.51)], Kangai injection [OR 2.16,95%CI (1.56,3.02)], and Shenqi Fuzheng injection [OR 1.97,95%CI (1.24,3.15)] combined with chemotherapy in colorectal cancer treatment had a significantly higher objective response rate (p < 0.05) than single chemotherapy, and compound Kushen injection + chemotherapy [OR 2.72,95%CI (2.12,3.51)] regimen ranked the highest. The disease control rate of Aidi injection, Brucea javanica oil emulsion injection [OR 4.1,95%CI (1.74,10.43)], compound Kushen injection [OR 2.43,95%CI (1.73,3.44), Kangai injection[OR 2.31,95%CI (1.51,3.58)], Kanglaite injection[OR 3.18,95%CI (1.52,6.9)], and Shenqi Fuzheng injection[OR 2.6,95%CI (1.22,5.92)] combined with chemotherapy in the treatment of colorectal cancer was significantly improved (p < 0.05), and Brucea javanica oil emulsion injection + chemotherapy[OR 4.1,95%CI (1.74,10.43)] regimen ranked the highest. The incidence of leukopenia reduction in the treatment of colorectal cancer was significantly reduced by Aidi injection[OR 0.32,95%CI (0.24,0.43)], Brucea javanica oil emulsion injection [OR 0.34,95%CI (0.17,0.68)] compound Kushen injection [OR 0.27,95%CI (0.17,0.40)], Kangai injection [OR 0.23,95%CI (0.14,0.37)], and Kanglaite injection [OR 0.20,95%CI (0.09,0.45)] combined with chemotherapy (p < 0.05), and Kanglaite injection + chemotherapy [OR 0.20,95%CI (0.09,0.45)] regimen ranked the highest. Aidi injection [OR 0.48,95%CI (0.3,0.74)], Brucea javanica oil emulsion injection [OR 0.09,95%CI (0.01,0.43)], and Kangai injection [OR 0.47,95%CI (0.22,0.96)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of thrombocytopenia reduction (p < 0.05), and Brucea javanica oil emulsion injection + chemotherapy [OR 0.09,95%CI (0.01,0.43)] regimen ranked the highest. Aidi injection [OR 0.49,95%CI (0.32, 0.74)], Kangai injection [OR 0.26,95%CI (0.09,0.71)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of hemoglobin reduction (p < 0.05), and Kangai injection + chemotherapy [OR 0.26,95%CI (0.09,0.71)] regimen ranked the highest. Aidi injection [OR 0.38,95%CI (0.28,0.52)], compound Kushen injection [OR 0.23,95%CI (0.15,0.36)] and Kangai injection [OR 0.19,95%CI (0.12,0.30)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of nausea and vomiting (p < 0.05), and Kangai injection + chemotherapy[OR 0.19,95%CI (0.12,0.30)] regimen ranked the highest. Aidi injection [OR 0.51,95%CI (0.35,0.74)], compound Kushenshen injection [OR 0.27,95%CI (0.15,0.47)], and Kanglaite injection [OR 0.31,95%CI (0.13,0.69)] combined with chemotherapy in the treatment of colorectal cancer significantly reduced the incidence of abdominal pain and diarrhea (p < 0.05), and compound Kushen injection + chemotherapy [OR 0.27,95%CI (0.15,0.47)] regimen ranked the highest. CONCLUSION: Aidi injection, Brucea javanica oil emulsion injection, compound Kushen injection, Kangai injection, Shenqi Fuzheng injection, Kanglaite injection, Shenfu injection, and Xiaoaiping injection combined with chemotherapy functioned more effectively than single chemotherapy did in colorectal cancer treatment. Nevertheless, limited by the treatment quality and methodology of different intervention measures included in the study, this conclusion is expected to be scrutinized in higher-quality and rigorously designed randomized controlled trials. PROSPERO registration No.: CRD42023392398.

Supplement Individual Article: A Reappraisal of Fixed-Combination Halobetasol Propionate and Tazarotene for the Treatment of Psoriasis: Biological Underpinnings, Therapeutic Mechanisms, and Economic Considerations.

Psoriasis is a complex inflammatory disease, which can be triggered by the interplay among keratinocytes, various immune cells, and even dermal vascular endothelial cells. Understanding of the key players and cytokine/chemokine messengers involved in the initiation and maintenance of psoriasis has significantly evolved and led to numerous systemic biologic therapies targeting those specific components. These therapies, despite their successes, do not ubiquitously affect all pathogenic cellular pathways. They also carry their risks and may be contraindicated in certain patient populations. Therefore, other therapeutics are still necessary. Tazarotene, a decades-old topical retinoid, has been successfully used for treating cutaneous psoriasis. Its retinoid effect via binding to retinoic acid receptors (RAR)/retinoic X receptors (RXR) alters cellular gene expression of numerous pathogenic cells and leads to a long-standing maintenance effect despite discontinuation - a phenomenon known as remittance. Concurrent use of tazarotene with topical corticosteroids results in reduced incidence of treatment-related adverse events. A fixed-combination lotion containing halobetasol propionate (HP) and tazarotene (HP 0.01%/TAZ 0.045%, Duobrii, Ortho Dermatologics) was developed implementing polymeric emulsion technology that demonstrates efficacy in psoriasis while mitigating adverse events associated with each component alone as monotherapy. In this paper, we review the pathogenesis of psoriasis and illuminate the effect of tazarotene and HP on key cellular pathways. In addition, we review the clinical efficacy of fixed-combination HP 0.01%/TAZ 0.045% lotion in psoriasis as well as its long-term treatment maintenance, applicability in skin of color, and beneficial economic impact for patients and healthcare stakeholders. As HP 0.01%/TAZ 0.045% lotion is safe and exhibits excellent efficacy, it should be within the therapeutic toolbox for every psoriasis patient.J Drugs Dermatol. 2023;22:1(Suppl 1):s3-10.

Antitumoral effect of local injection of TLR-9 agonist emulsified in Lipiodol with systemic anti-PD-1 in a murine model of colorectal carcinoma.

Introduction: Local treatments of cancer, including transarterial chemoembolization, could enhance responses to systemic immune checkpoint inhibitors such as anti-PD-1 antibodies. Lipiodol, a radiopaque oil, is widely used for transarterial chemoembolization as a tumor-targeting drug carrier and could be used in emulsion with immunomodulators. This study aimed at evaluating the antitumoral effect of intra-tumoral injection of Lipiodol-immunomodulator emulsions combined with systemic anti-PD-1 therapy in a murine model of colorectal carcinoma. Method: Mice (male BALB/c) with anti-PD-1-resistant subcutaneous CT26 tumors were injected with immunomodulators, emulsified or not with Lipiodol (N=10-12/group). Results: The TLR-9 agonist CpG displayed antitumor effects, while Poly I:C and QS21 did not. The Lipiodol-CpG emulsion appeared to be stable and maintained CpG within tumors for a longer time. Repeated intra-tumoral injections, combined with anti-PD-1, induced responses towards the tumor as well as to a distant metastatic-like nodule. This treatment was associated with an increase in proliferative CD8+ T cells and of IFN-γ expression, a decrease in proliferative regulatory T cells but also, surprisingly, an increase in myeloid derived suppressor cells. Conclusions: Local administration of CpG emulsified with Lipiodol led to an effective antitumoral effect when combined to systemic anti-PD-1 therapy. Lipiodol, apart from its radiopaque properties, is an efficient drug-delivery system. The formulated oil-in-water emulsion allows efficient loading and control release of CpG, which induces favorable immune modifications in this murine tumor model.

Polymersome-stabilized doxorubicin-lipiodol emulsions for high-efficacy chemoembolization therapy.

Transarterial chemoembolization (TACE) with free doxorubicin-lipiodol emulsions (free DOX/L) is a favored clinical treatment for advanced hepatocellular carcinoma (HCC) patients ineligible for radical therapies; however, its inferior colloidal stability not only greatly reduces its tumor retention but also hastens drug release into blood circulation, leading to suboptimal clinical outcomes. Here, we find that disulfide-crosslinked polymersomes carrying doxorubicin (Ps-DOX) form super-stable and homogenous water-in-oil microemulsions with lipiodol (Ps-DOX/L). Ps-DOX/L microemulsions had tunable sizes ranging from 14 to 44 µm depending on the amount of Ps-DOX, were stable over 2 months storage as well as centrifugation, and exhibited nearly zero-order DOX release within 15 days. Of note, Ps-DOX induced 2.3-13.4 fold better inhibitory activity in all tested rat, murine and human liver tumor cells than free DOX likely due to its efficient redox-triggered intracellular drug release. Interestingly, transarterial administration of Ps-DOX/L microemulsions in orthotopic rat N1S1 syngeneic HCC model showed minimal systemic DOX exposure, high and long hepatic DOX retention, complete tumor elimination, effective inhibition of angiogenesis, and depleted adverse effects, significantly outperforming clinically used free DOX/L emulsions. This smart polymersome stabilization of doxorubicin-lipiodol microemulsions provides a novel TACE strategy for advanced tumors.

Calcium sulfate beads made with antibacterial essential oil-water emulsions exhibit growth inhibition against Staphylococcus aureus in agar pour plates.

Calcium sulfate bone void filler beads are fully absorbable in the body, and are often used in complicated orthopedic infection cases to release a relatively high dose of antibiotics locally to the body site over time. However, the antibiotic resistance crisis and/or inability to treat chronic biofilm infections remains to be a formidable and increasing health threat. In this report, we tested the hypothesis that plant essential oils (PEOs) with anti-staphylococcal qualities could inhibit the growth of Staphylococcus aureus (a major etiological agent of periprosthetic joint infection) in agar pour plates when infused in calcium sulfate beads. To begin, we conducted a screen of 57 single plant PEOs for anti-staphylococcal activity via disk diffusions assays. We observed that 55/57 of the PEOs had significant growth inhibitory activity compared to the null hypothesis, and 41/57 PEOs exhibited activity similar-to-or-higher-than a vancomycin minimum inhibitory control. When PEOs were infused in beads, we observed that 17/57 PEOs tested exhibited significant bacterial growth inhibition when encased in S. aureus-seeded agar compared to a null hypothesis of six millimeters (bead size). However, none of the PEO-beads had activity similar to a vancomycin bead control made according to a clinically relevant formula. To the best of our knowledge, this is the first report and screen of PEOs for growth inhibitory activity when infused in lab-made calcium sulfate beads. These data indicate that antibacterial PEOs warrant further investigations, and may be useful in developing new treatment strategies for periprosthetic joint infection.

Efficacy and safety of Brucea javanica oil emulsion injection as adjuvant therapy for cancer: An overview of systematic reviews and meta-analyses.

BACKGROUND: In China, Brucea javanica oil emulsion injection (BJOEI) has been used as adjuvant therapy to treat cancer for many years. Many systematic reviews (SRs) or meta-analyses (MAs) were published to evaluate its efficacy and safety. Nevertheless, uneven quality made it difficult to reach a consensus and there has been no specific review to integrate the evidence of BJOEI for cancer at present. Therefore, a comprehensive evidence map is needed to guide clinicians. PURPOSE: We, for the first time, conducted an overview to assess the SRs/MAs of BJOEI, and provided a comprehensive evidence map to guide clinicians. Besides, this study provided a promising direction for future research to promote the generation of advanced evidence. STUDY DESIGN: An overview of SRs or MAs. METHODS: The pre-defined search strategies were applied to 8 databases. Suitable SRs/MAs were included according to the inclusion and exclusion criteria. Methodological quality, reporting quality, and risk of bias were assessed. An evidence map was conducted to show the situation of clinical evidence. RESULTS: 27 SRs/MAs in 7 cancer types were included in this overview. The main problems of SRs/MAs were concentrated on the following aspects: without registration or protocol, lacking gray literature retrieval and a list of excluded studies, incomplete description in the literature retrieval strategy or the methods of merging results, the bias of each synthetic result, less exploration in heterogeneity or publication bias, deficiencies in assessing evidence quality and less description in conflict, funding or access to relevant information. Based on the rules of GRADE, the evidence quality of 154 items in 27 SRs/MAs was defined as moderate quality (103 items), low-quality (44 items), and very low-quality (7 items). Especially, risk of bias (154 items), imprecision (27 items), inconsistency (20 items), and publication bias (9 items) were the main downgrading factors. CONCLUSION: BJOEI may be a promising adjuvant therapy for treating cancer, especially in the digestive system. However, high-quality SRs/MAs are expected to be carried out to improve the reliability of the above conclusion in the future.

Efficacy of Aidi Injection and Brucea javanica Oil Emulsion Injection in Rectal Cancer during CapeOX Adjuvant Chemotherapy.

BACKGROUND: Adjuvant chemotherapy with CapeOX regimen is widely used in resected rectal cancer, which brings benefits to patients. But drug-related toxicities are severe during this process; thus, survival outcomes may potentially be affected. This study explored the efficacy of two Chinese herbal injections, Aidi injection (ADI) and Brucea javanica oil emulsion injection (BJOEI), as adjuvant drugs in CapeOX adjuvant chemotherapy on rectal cancer patients. METHODS: A total of 240 cases were enrolled in this retrospective study. 80 cases received CapeOX with ADI (the ADI group), 80 cases received CapeOX with BJOEI (the BJOEI group), and the rest 80 cases received CapeOX alone (the control group). After four cycles' chemotherapy, adverse reactions (ADRs) and quality of life (QOL) were analyzed. Then, patients received follow-up for at least one year, and the endpoint was disease-free survival (DFS). RESULTS: All patients completed at least four cycles' adjuvant chemotherapy. The incidence of leukopenia and thrombocytopenia was significantly lower in the ADI group; the incidence of nausea was significantly lower in the BJOEI group; the incidence of hand-foot syndrome was significantly lower in both the ADI group and BJOEI group. Significant difference was found in the control group regarding the Karnofsky Performance Status (KPS) scores prior and posttreatment. No difference was found among three groups regarding one-year DFS. CONCLUSION: As adjuvant drugs for rectal cancer during CapeOX chemotherapy, ADI shows advantages in decreasing leukopenia and thrombocytopenia, while BJOEI results better in remitting nausea. Both two CHIs had positive impacts on decreasing hand-foot syndrome and the maintenance of patients' QOL. It is worthy of further study and promotion for CHIs.

Andiroba oil and nanoemulsion (Carapa guianensis Aublet) reduce lesion severity caused by the antineoplastic agent doxorubicin in mice.

Doxorubicin (DOX) is an anthracycline antibiotic used in the fight against many types of cancer. Although it is quite effective for this purpose, its clinical use is limited by its severe side effects, highlighting the relevance of efforts to identify substances that act to minimize these effects. In this work, we sought to verify the ability of andiroba oil (AO) and a nanoemulsion of andiroba oil (AN) to lessen the side effects of DOX. The animals were separated into 7 groups with 6 animals each: mice treated with AO (2000 mg/kg), AN (2000 mg/kg), the antineoplastic agent DOX (40 mg/kg), AO+DOX, AN+DOX and solvent controls was used of negative control (corn oil and nanoemulsion surfactant). AO and AN were administered for 14 consecutive days orally by gavage and on the 13th day, applied DOX by intraperitoneal route (i.p.), in order to evaluate the protective potential of andiroba. The animals were euthanized on the 15th day. Hematological, biochemical, histological, and immunohistochemical parameters were analyzed. Andiroba reduced several aspects of the severity of lesions caused by DOX, decreasing hematotoxicity and the severity of histological changes in the liver and kidneys, and reducing the frequency of apoptotic cell death. In many cases, AN showed greater efficacy than AO alone, reflecting the feasibility of using this nanotechnology to improve the pharmacokinetics of lipid compounds in the body. The study sheds new light on the therapeutic benefits of andiroba and suggests new ways for investigating how the quantity and quality of lipid compounds affect exposed organisms.

PLACK syndrome is potentially treatable with intralipids.

We describe an 11-year-old girl with PLACK Syndrome (peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads), who was found to have a novel homozygous variant in CAST, the pathogenicity of which was confirmed using blood-derived RNA. There is no established treatment for PLACK syndrome. However, we demonstrate for the first time that this condition is associated with low levels of vitamin A and essential fatty acids, which prompted us to consider a potential treatment strategy. Indeed, we initiated this patient on intravenous lipid infusion (Vitalipid®; an emulsion of fat-soluble vitamins and lipofundin-MCT/LCT 20%) and the response was dramatic. Following the fourth monthly course of treatment, pruritis disappeared and the skin lesions showed remarkable objective improvement. PLACK syndrome is a very rare genodermatosis and only six families have been described to date with pathogenic CAST variants. This is the first report of an objective response to a therapeutic agent, which suggests that PLACK is a potentially treatable condition. The remarkable response we report and the relative safety of the intervention should prompt healthcare providers who care for PLACK syndrome patients to explore this as a potential treatment strategy in future studies.

Efficacy of a Glass Membrane Emulsification Device to Form Mixture of Cisplatin Powder with Lipiodol on Transarterial Therapy for Hepatocellular Carcinoma.

PURPOSE: To examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock. MATERIALS AND METHODS: Seven different types of mixtures were evaluated: cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (emulsion), incomplete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (solid-in-water emulsion), and contrast material and cisplatin suspension mixed by a 3-way stopcock or the device (solid-in-oil emulsion). RESULT: The percentages of water-in-oil were 98.08 ± 0.27% in the emulsion formed by the device, while 70.3 ± 4.63% in the emulsion formed by a 3-way stopcock (P = 0.037). Solid-in-water and solid-in-oil emulsions formed by the device showed 98.09 ± 0.38% and 98.70 ± 0.40% of water-in-oil, respectively, whereas both solid-in-water and solid-in-oil emulsions formed by a 3-way stopcock showed 0.00%. Homogenous droplet sizes were shown by using the device. The half release times of cisplatin in the emulsions formed by the device were 197 ± 19, 244 ± 24 and 478 ± 52 min, respectively, which were significantly longer than the emulsion formed by a 3-way stopcock of 8 ± 8 min (P = 0.046-0.050). Suspension showed the longest release time; however, the viscosity was lowest. CONCLUSION: The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device.

Efficacy and safety of Brucea javanica oil emulsion for liver cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Brucea javanica oil emulsion (BJOE), extracted from the Chinese herb Bruceae Fructus (Yadanzi), is a broad-spectrum anti-tumor drug and has been widely used for the treatment of liver cancer in China. The aim of this study is to systematically investigate the efficacy and safety of BJOE for the treatment of liver cancer. METHODS: Seven electronic databases including the Cochrane Library, PubMed, Excerpt Medica Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Scientific Journal Database, and Wanfang Database will be systematically retrieved for data extraction from their inceptions to September 2020. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger test. The quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal or presenting the findings at a relevant conference. CONCLUSION: The conclusion of this study will provide helpful evidence of the effect and safety of BJOE for the treatment of liver cancer in clinical practice. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/UC8XQ.

Peptide vaccine with glucopyranosyl lipid A-stable oil-in-water emulsion for patients with resected melanoma.

Aim: We tested the safety and immunogenicity of a novel vaccine in patients with resected high-risk melanoma. Patients & methods: HLA-A2-positive patients with resected Stage II-IV melanoma were randomized to receive up to three vaccinations of melanoma-associated peptide (MART-1a) combined with a stable oil-in-water emulsion (SE) either with the Toll-like receptor 4 agonist glucopyranosyl lipid A (GLA-SE-Schedule 1) or alone (SE-Schedule 2). Safety and immunogenicity of the vaccines were monitored. Results: A total of 23 patients were registered. No treatment-related grade 3 or higher adverse events were observed. Increases in MART-1a-specific T cells were seen in 70 and 63% of Schedule 1 and Schedule 2 patients, respectively. Conclusion: Both vaccine schedules were well-tolerated and resulted in an increase in MART-1a-specific T cells. Clinical Trial registration: NCT02320305 (ClinicalTrials.gov).

In vivo evaluation of a monodisperse solid-in-oil-in-water miriplatin/ lipiodol emulsion in transcatheter arterial chemoembolization using a rabbit VX2 tumor model.

Transcatheter arterial chemoembolization (TACE) is a standard treatment for unresectable hepatocellular carcinoma; however, it does not always result in tumor control. Nevertheless, treatment outcome can be improved with monodisperse emulsions of anticancer agents. In this study, the distribution of a monodisperse miriplatin-Lipiodol emulsion in the tumor and its safety were evaluated in ten Japanese white rabbits. VX2 tumor was implanted into the left liver lobe. The animals were divided into control and experimental groups (of five animals each) and respectively administered a conventional miriplatin suspension or the emulsion via the left hepatic artery. Computed tomography (CT) was performed before, immediately after, and two days following TACE. All rabbits were sacrificed two days after the procedure. Each tumor was removed and cut in half for assessment of iodine concentration in one half by mass spectroscopy and evaluation of Lipiodol accumulation and adverse events in the other half. Mean Hounsfield unit (HU) values were measured using plain CT images taken before and after TACE. Iodine concentration was higher in the experimental group [1100 (750-1500) ppm, median (range)] than in the control group [840 (660-1800) ppm], although statistically not significant. Additionally, the HU value for the experimental group was higher than that for the control group immediately after [199.6 (134.0-301.7) vs. 165.3 (131.4-280.5)] and two days after [114.2 (56.1-229.8) vs. 58.3 (42.9-132.5)] TACE, although statistically not significant. Cholecystitis was observed in one rabbit in the control group. Ischemic bile duct injury was not observed in any group. The results show that Lipiodol accumulation and retention in VX2 tumor can possibly be improved with a monodisperse emulsion; however, it should be verified with a larger study. Moreover, no significant adverse events are associated with the use of the emulsion.

A Supersaturated Oxygen Emulsion for Wound Care and Skin Rejuvenation.

Although oxygen is essential for proper wound healing, wounds are often hypoxic with diminished oxygen delivery to the healing tissue. Since oxygenation of the outer layers of skin is almost exclusively provided by the atmosphere, increasing the presence of external oxygen enhances the healing process. Hyperbaric oxygen therapy is beneficial for treating nonhealing wounds, such as diabetic ulcers, and has been used to speed post-treatment recovery following aesthetic procedures; however, it is not suitable for home use. Recently, perfluorocarbon emulsions have been developed that can absorb large amount of oxygen. Preparations containing 2% of these compounds can absorb up to seven-times more oxygen than water at 37°C. A topical perfluorocarbon emulsion consisting of perfluorodecalin, water, plant derived emulsifiers, and a preservative, has been developed for use in dermatology (Cutagenix™ & Cutavive™ Professional Skin Care Emulsion; Cutagenesis, Niwot, CO). Designed to be applied 2 to 4 times daily following skin rejuvenation procedures, this topical oxygen emulsion reduces the incidence of post-procedure complications. The application of a topical emulsion is well-suited for patient application to enhance recovery following energy-based aesthetic procedures. J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4728.