Concentrate of proteolytic enzymes enriched in bromelain 5g powder and gel for gel vials

Background: NexoBrid® (NXB; MediWound Ltd., Yavne, Israel) (anacaulase-bcdb) is a bromelain-based enzymatic debriding agent approved for eschar removal in burn care. Despite widespread clinical use, histological evidence of tissue-level changes after enzymatic debridement remains limited. This systematic review aimed to evaluate preclinical and clinical studies describing histological findings following bromelain-based enzymatic debridement of thermal burns. Methods: Following PRISMA 2020 guidelines, we performed parallel systematic searches of preclinical (animal) and clinical (human) studies across PubMed, Embase, CENTRAL, Web of Science, and Scopus. Included studies reported thermal burns treated with bromelain-based enzymatic debridement and tissue biopsies with histological analysis. Quality was assessed using the SYRCLE Risk of Bias Tool (preclinical) and JBI Critical Appraisal Checklists (clinical). Results: Six preclinical studies (five porcine, one rat) met inclusion criteria. Findings included: selective eschar removal with dermal preservation; protection of the zone of stasis (67% partial- vs. 100% full-thickness necrosis; p = 0.05); viable dermal thickness of 1.1 ± 0.7 mm; and accelerated re-epithelialization (7.4 ± 0.8 vs. 9.1 ± 2.1 days; p < 0.05). Only two clinical studies (n = 9 patients) met the inclusion criteria: one case series (n = 8) and one case report. Clinical findings showed upper dermal homogenisation with preserved deep dermis, vascular congestion correlating with pinpoint bleeding, and pseudoeschar formation via transepidermal elimination. Conclusions: Preclinical evidence supports selective enzymatic debridement with dermal preservation. However, clinical histological data are limited to nine patients after over 13 years of use. This highlights a critical translational gap and underscores the need for prospective clinical histological studies.

Abstract licence: CC BY

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease all over the world due to the obesity pandemic; currently, therapeutic options for NAFLD are scarce, except for diet recommendations and physical activity. NAFLD is characterized by excessive accumulation of fat deposits (>5%) in the liver with subsequent inflammation and fibrosis. Studies in the literature show that insulin resistance (IR) may be considered as the key mechanism in the onset and progression of NAFLD. Recently, using natural products as an alternative approach in the treatment of NAFLD has drawn growing attention among physicians. In this review, the authors present the most recent randomized controlled trials (RCTs) and lines of evidence from animal models about the efficacy of nutraceutics in alleviating NAFLD. Among the most studied substances in the literature, the following molecules were chosen because of their presence in the literature of both clinical and preclinical studies: spirulina, oleuropein, garlic, berberine, resveratrol, curcumin, ginseng, glycyrrhizin, coffee, cocoa powder, epigallocatechin-3-gallate, and bromelain.

Abstract licence: CC BY

Bromelain is a complex combination of multiple endopeptidases of thiol and other compounds derived from the pineapple fruit, stem and/or root. Fruit bromelain and stem bromelain are produced completely distinctly and comprise unique compounds of enzymes, and the descriptor "Bromelain" originally referred in actuality to stem bromelain. Due to the efficacy of oral administration in the body, as a safe phytotherapeutic medication, bromelain was commonly suited for patients due to lack of compromise in its peptidase efficacy and the absence of undesired side effects. Various in vivo and in vitro studies have shown that they are anti-edematous, anti-inflammatory, anti-cancerous, anti-thrombotic, fibrinolytic, and facilitate the death of apoptotic cells. The pharmacological properties of bromelain are, in part, related to its arachidonate cascade modulation, inhibition of platelet aggregation, such as interference with malignant cell growth; anti-inflammatory action; fibrinolytic activity; skin debridement properties, and reduction of the severe effects of SARS-Cov-2. In this paper, we concentrated primarily on the potential of bromelain's important characteristics and meditative and therapeutic effects, along with the possible mechanism of action.

Abstract licence: CC BY

Meat processing involves different transformations in the animal muscle after slaughtering, which results in changes in tenderness, aroma and colour, determining the quality of the final meat product. Enzymatic glycolysis, proteolysis and lipolysis play a key role in the conversion of muscle into meat. The accurate control of enzymatic reactions in meat muscle is complicated due to the numerous influential factors, as well as its low reaction rate. Moreover, exogenous enzymes are also used in the meat industry to produce restructured products (transglutaminase), to obtain bioactive peptides (peptides with antioxidant, antihypertensive and gastrointestinal activity) and to promote meat tenderization (papain, bromelain, ficin, zingibain, cucumisin and actinidin). Emerging technologies, such as ultrasound (US), pulsed electric fields (PEF), moderate electric fields (MEF), high-pressure processing (HPP) or supercritical CO2 (SC-CO2), have been used to intensify enzymatic reactions in different food applications. This review aims to provide an overview of the enzymatic reactions taking place during the processing of meat products, how they could be intensified by using emerging technologies and envisage potential applications.

Abstract licence: CC BY

Background: Debridement is considered the first step in treatment of chronic wounds, however, current enzymatic and autolytic debridement agents are slow or ineffective. Previous studies have shown positive initial results with EscharEx® (EX-02 formulation), a Bromelain-based enzymatic debridement agent in development for chronic wounds. The main objective of this study was to assess its efficacy in debriding venous leg ulcers (VLU), compared to gel vehicle (GV) as a placebo control and to non-surgical standard of care (NSSOC). Methods: A prospective, randomized, multicenter, placebo-controlled trial in patients with VLU from 20 medical centers and clinics in the United States, Switzerland and Israel was undertaken. Patients were treated with daily topical applications of either EX-02, GV, or NSSOC (in a 3:3:2 ratio), until reaching complete debridement or up to 8 daily treatments (within 2 weeks), and then followed-up for up to 14 weeks. The primary efficacy endpoint was the incidence of complete debridement. This study is registered with ClinicalTrials.gov (NCT03588130) and EudraCT (number 2020-004861-38). Findings: A total of 196 patients were enrolled, and 119 randomized (between November 12th, 2019, and February 15th, 2022); 46 to the EX-02 arm, 43 to the GV arm, and 30 to the NSSOC arm. Eight patients dropped out of the study (2 in EX-02, 2 in GV, 4 in NSSOC). The incidence of complete debridement within 8 daily treatments was 63% (29/46 patients) in the EX-02 arm as compared to 30.2% (13/43 patients) in the GV arm (p = 0.004) and 13.3% (4/30 patients) in the NSSOC arm (p < 0.001). Sixty-five patients reported wound related adverse events throughout the study; 24 (52.2%), 27 (62.8%) and 14 (46.7%) patients in the EX-02, GV and NSSOC arms (p = NS). No deaths occurred during the study. Interpretation: EX-02 lead to a significantly higher incidence of complete debridement as compared to GV and NSSOC, without significant safety issues. Additional studies are needed to explore the benefits of EX-02 in VLU and other chronic wound etiologies. Funding: MediWound Ltd.

Abstract licence: CC BY-NC-ND

Background/Objectives: Basal cell carcinoma (BCC), the most prevalent form of human cancer, is traditionally treated by surgical and alternative destructive or topical chemical means, each with its advantages, challenges, and drawbacks. We describe our experience treating BCCs with a topical concentrate of proteolytic enzymes enriched in bromelain (CPEEB) sourced from pineapple stems. CPEEB has strong proteolytic, antitumor–proapoptotic, and inflammation modulation activities, and is approved for debridement of deep burns and starting phase 3 trials for chronic wounds. Methods: In the first proof-of-concept (POC) study, six BCCs on three individuals were treated with five to six daily CPEEB 10% topical applications under a zinc oxide-based occlusive dressing for 9–12 h each during a period of up to 10 days. These patients were followed for up to 4 years. In an additional two POC studies, 16 patients with one BCC each were treated every other day for a total of seven applications of topical CPEEB 5% under a variety of occlusive dressings. The wounds were followed for up to 2 months before undergoing diagnostic excisional biopsy. Results: In the first study, clinical assessment of the BCCs and two excisional biopsies after 6 months suggested that all lesions were eradicated with spontaneous healing within ~2 weeks without clinical or histological recurrence for over 4 years. In the two subsequent studies, 16 histologically diagnosed superficial and nodular BCCs were treated using four application techniques. Excisional histology after 2 months confirmed BCC eradication in seven of the patients. In nine patients, with compromised occlusive dressings, histological eradication was incomplete. Treatment was well tolerated by all patients with the expected local skin reactions, which completely healed within 2–3 weeks. Conclusions: These are POC preliminary studies aimed at indicating the potential efficacy and feasibility of topical CPEEB in eradicating BCC. In these studies, topical CPEEB 10% and 5% resulted in complete eradication of the BCC when appropriately applied. CPEEB was well tolerated in all patients, and all treated sites’ erosions healed without scars in &lt;3 weeks. Further research is necessary to corroborate the results, refine the application technique, and complete the regulatory process.

Abstract licence: CC BY

The management of severe burns is a complex process that requires a multidimensional approach to ensure optimal healing of burn wounds, minimize complications, and improve the prognosis of patients. Surgical debridement is considered the gold standard for removing necrotic tissue; however, this approach involves risks such as bleeding, the potential removal of viable tissue during excision, and technical challenges in complex anatomical areas. Recent advancements highlight the role of enzymatic debridement using NexoBrid®, which offers a less invasive alternative to surgical excision while having the ability to selectively debride necrotic tissue and preserve viable tissue. NexoBrid® has shown efficacy in reducing debridement time, minimizing the need for additional surgeries, and improving overall wound healing outcomes. This review discusses the clinical indications, advantages, and considerations for choosing between surgical and enzymatic debridement. Emerging studies suggest the potential for enzymatic debridement to be safe and effective even for larger burn areas, making it a promising option in modern burn care. However, ongoing evaluation and integration into clinical protocols will be essential to fully realize its benefits in specialized burn treatment and to establish protocols.

Abstract licence: CC BY