Natural rubber latex-based biomaterials for drug delivery and regenerative medicine: Trends and directions.

Natural Rubber Latex (NRL) has shown to be a promising biomaterial for use as a drug delivery system to release various bioactive compounds. It is cost-effective, easy to handle, biocompatible, and exhibits pro-angiogenic and pro-healing properties for both soft and hard tissues. NRL releases compounds following burst and sustained release kinetics, exhibiting first-order release kinetics. Moreover, its pore density can be adjusted for tailored kinetics profiles. In addition, biotechnological applications of NRL in amblyopia, smart mattresses, and neovaginoplasty have demonstrated success. This comprehensive review explores NRL's diverse applications in biotechnology and biomedicine, addressing challenges in translating research into clinical practice. Organized into eight sections, the review emphasizes NRL's potential in wound healing, drug delivery, and metallic nanoparticle synthesis. It also addresses the challenges in enhancing NRL's physical properties and discusses its interactions with the human immune system. Furthermore, examines NRL's potential in creating wearable medical devices and biosensors for neurological disorders. To fully explore NRL's potential in addressing important medical conditions, we emphasize throughout this review the importance of interdisciplinary research and collaboration. In conclusion, this review advances our understanding of NRL's role in biomedical and biotechnological applications, offering insights into its diverse applications and promising opportunities for future development.

Recent advances and perspectives on natural latex serum and its fractions for biomedical applications.

Advances and the discovery of new biomaterials have opened new frontiers in regenerative medicine. These biomaterials play a key role in current medicine by improving the life quality or even saving the lives of millions of people. Since the 2000s, Natural Rubber Latex (NRL) has been employed as wound dressings, mechanical barrier for Guided Bone Regeneration (GBR), matrix for drug delivery, and grafting. NRL is a natural polymer that can stimulate cell proliferation, neoangiogenesis, and extracellular matrix (ECM) formation. Furthermore, it is well established that proteins and other biologically active molecules present in the Natural Latex Serum (NLS) are responsible for the biological properties of NRL. NLS can be obtained from NRL by three main methods, namely (i) Centrifugation (fractionation of NRL in distinct fractions), (ii) Coagulation and sedimentation (coagulating NRL to separate the NLS from rubber particles), and (iii) Alternative extraction process (elution from NRL membrane). In this review, the chemical composition, physicochemical properties, toxicity, and other biological information such as osteogenesis, vasculogenesis, adhesion, proliferation, antimicrobial behavior, and antitumoral activity of NLS, as well as some of its medical instruments and devices are discussed. The progress in NLS applications in the biomedical field, more specifically in cell cultures, alternative animals, regular animals, and clinical trials are also discussed. An overview of the challenges and future directions of the applications of NLS and its derivatives in tissue engineering for hard and soft tissue regeneration is also given.

Natural latex serum: characterization and biocompatibility assessment using Galleria mellonella as an alternative in vivo model.

Natural latex serum (NLS) is one of the natural rubber latex fractions from Hevea brasiliensis tree, which is formed by centrifuged serum and is composed of proteins, acids, nucleotides, salts and carbohydrates. The proteins present in NLS have demonstrated several interesting biological properties, including angiogenic, healing, osteogenic, anti-inflammatory, antimicrobial, in addition to inducing neovascularization, bone formation and osseointegration. Thus, we proposed to characterize NLS by physicochemical techniques and to investigate the biocompatibility by toxicological assays and safety test in Galleria mellonella. Infrared spectrum showed vibrational bands characteristic of amide I, II and III that are linked to the protein content, which was confirmed by the High Performance Liquid Chromatography profile and by the Electrophoresis analysis. This material did not exhibit hemolytic (rate <0.5%) and cytotoxic effects (viability >70%) and was able to enhance the proliferation of fibroblasts (>600%) after 3 days. The pronounced proliferative effect observed in fibroblast cells can be explained by the presence of the fibroblast growth factor (FGF) like protein revealed by the Western blot test. Moreover, NLS did not provoke toxic effects (survival ∼ 80%) on the G. mellonella model, indicating that it is a biocompatible and safe material.

Ibuprofen-loaded biocompatible latex membrane for drug release: Characterization and molecular modeling.

The incorporation of drugs and bioactive compounds in the natural rubber latex (NRL) matrix has been an alternative for the development of transdermal release membranes. Ibuprofen (IBF) is known to be used to treat inflammatory diseases, but when administered orally, high concentrations can cause some adverse problems. In this work, the incorporation of IBF in the NRL membranes was evaluated by physical-chemical, in vitro permeation, hemocompatibility and molecular modeling assays. In addition, the in vitro release profile of IBF in acid and basic media was analyzed during 96 h. The IBF-NRL membrane exhibited the absence of intermolecular bonding that could hinder drug release and presented compatible mechanical properties for applications as a cutaneous adhesive (0.58 and 1.12 MPa to Young's modulus and rupture tension, respectively). The IBF-NRL system did not present a significant hemolysis degree (1.67%) within 24 h. The release test indicated that in the first hours of the study, 48.5% IBF was released at basic pH and 22.5% at acidic pH, which is characteristic of a burst effect. Then, a stable release profile was observed until the end of the assay, with total IBF release of 60% in alkaline medium and 50% in acidic medium. The drug permeation results indicated that the IBF-NRL membranes can be used for the local skin treatment with permeation of 3.11% of IBF. Dynamic Molecular simulations indicated a pronounced electric dipole in the ionized form of IBF, which suggests a more effective interaction with water, explaining the efficient drug release in alkaline solutions. In general, the results demonstrate that the IBF-NRL membrane has great potential for a new adhesive that can be used for the treatment of inflammatory processes and injuries.

Natural latex-glycerol dressing to reduce nipple pain and healing the skin in breastfeeding women.

BACKGROUND: Nipple pain is the second most common reason for early weaning, exceeded only by the insufficient milk supply. Nipple fissures can bring other problems, acting also as a portal for bacteria and leading to mastitis. This work proposes the breast protector composite development using materials with tissue repair and moisturizing properties, aligned with a low-cost procedure, aiming not only to relieve pain, but also to heal the nipple fissures caused by breastfeeding. MATERIALS AND METHODS: For the dressings, production was used Natural Latex extracted from the rubber tree and glycerol. The Samples were evaluated chemically and physically by the techniques of Scanning Electron Microscopy, Fourier transform infrared spectroscopy, mechanical traction, and contact angle. The samples were also biologically evaluated by the hemolytic and cytotoxic activity assays. RESULTS: From the physical-chemical assays, the matrix with glycerol has high pore density; the natural latex and glycerol do not covalently interact, indicating that the glycerol can be released; the glycerol addition makes the matrix more elastic but fragile, and increase the wettability. From the biological assays, both materials showed no hemolytic effects; and the cytotoxicity results showed that glycerol did not present cytotoxicity in the fibroblasts, but show a dose-dependent influence in the keratinocytes. CONCLUSION: The material developed for application in breast fissures has mechanical properties similar to those found for materials for dermal applications, present high wettability and pore density. Furthermore, the material showed no cytolytic activity and the tests with skin cell cultures demonstrated the biocompatibility.

Natural rubber latex coated with calcium phosphate for biomedical application.

Natural rubber latex (NRL) is a flexible biomembrane that possesses angiogenic properties and has recently been used for guided bone regeneration, enhancing healing without fibrous tissue, allergies or rejection. Calcium phosphate (Ca/P) ceramics have chemical, biological, and mechanical properties similar to mineral phase of bone, and ability to bond to the host tissue, although it can disperse from where it is applied. Therefore, to create a composite that could enhance the properties of both materials, NRL biomembranes were coated with Ca/P. NRL biomembranes were soaked in 1.5 times concentrated SBF solution for seven days, avoiding the use of high temperatures. SEM showed that Ca/P has been coated in NRL biomembrane, XRD showed low crystallinity and FTIR showed that is the carbonated type B. Furthermore, hemolysis of erythrocytes, quantified spectrophotometrically using materials (Ca/P, NRL, and NRL + Ca/P) showed no hemolytic effects up to 0.125 mg/mL (compounds and mixtures), indicating no detectable disturbance of the red blood cell membranes. The results show that the biomimetic is an appropriate method to coat NRL with Ca/P without using high temperatures, aiming a new biomembrane to improve guided bone regeneration.