BIOTECHNOLOGICAL INNOVATION AND CLINICAL EFFICACY OF PAPAIN IN WOUND REPAIR: FROM SUSTAINABLE EXTRACTION TO SYNERGY WITH PHOTOBIOMODULATION
DOI:
https://doi.org/10.63330/sasciencesv6n2-135Keywords:
Biotechnology, Enzymatic Debridement, Papain, Photobiomodulation, Wound HealingAbstract
The management of complex wounds presents a major clinical and economic challenge, requiring strategies that combine efficient enzymatic debridement with tissue regeneration stimulation. Papain, a proteolytic enzyme extracted from Carica papaya L., stands out for its selective degradation of devitalized tissue without harming healthy parenchyma. Concurrently, advances in bioprocesses have driven sustainable extraction methods and immobilization into nanostructured matrices, enhancing its physicochemical stability and commercial viability. Combining papain with photobiomodulation (PBM) emerges as a promising synergistic approach, acting simultaneously on wound bed cleansing and mitochondrial bioenergetic stimulation. This study aimed to analyze scientific evidence regarding the biotechnological innovation of papain and its synergistic potential with photobiomodulation in tissue repair. This is an integrative literature review developed according to Whittemore and Knafl's framework, mapping extraction routes, delivery systems, critical safety aspects, and clinical outcomes across international databases (PubMed, ScienceDirect, Scopus, SciELO, and Web of Science). Findings indicate that phototherapy enhances neovascularization, collagen synthesis, and oxidative stress control, complementing papain's enzymatic action. It is concluded that this technological integration represents a significant advancement in advanced wound care, although clinical protocol standardization remains an expanding field.
Downloads
References
ADEYI, O.; et al. Process optimization, scale-up studies, economic analysis and risk assessment of phenolic-rich bioactive extracts production from Carica papaya L. leaves via heat-assisted extraction technology. Heliyon. 2022;8(3):e09216.
BEKAVAC, N.; et al. Advancements in aqueous two-phase systems for enzyme extraction, purification, and biotransformation. Molecules. 2024;29(16):3776.
BHADANGE, Y. A.; CARPENTER, J.; SAHARAN, V. K. A comprehensive review on advanced extraction techniques for retrieving bioactive components from natural sources. ACS Omega. 2024;9(29):31274-31297.
BORELLA, J.; et al. Avaliação da estabilidade e da atividade enzimática de soluções de papaína utilizadas no desbridamento e cicatrização de feridas. Revista de Ciências Farmacêuticas Básica e Aplicada. 2016;28(3):179-184.
CANSINO-JÁCOME, F.; et al. Extraction of bioactive compounds from papaya leaves (Carica papaya L.) by multistage countercurrent extraction as function of solvent polarity and temperature. Food Chemistry. 2025;488:144824.
DE ARAÚJO, I.; et al. Fibrin gel versus papain gel in the healing of chronic venous ulcers: A double-blind randomized controlled trial. Phlebology. 2017;32(7):488-495.
DKHAR, K.; et al. Plant-derived proteolytic enzymes in modern regenerative medicine: Biocompatibility and immunological compliance. Biomedical Materials. 2025;20(2):025001.
FERREIRA, C.; et al. Synthesis and characterization of antibacterial poly{2-[(methacryloyloxy)ethyl trimethylammonium chloride}/chitosan semi-interpenetrating networks for papain release. Macromolecular Bioscience. 2025;25(1):e2400537.
FILHO, R.; et al. Papain immobilized on alginate membrane for wound dressing application. Colloids and Surfaces B: Biointerfaces. 2020;194:111222.
FRANSISKA, D.; et al. Physicochemical characterization of kappa-iota carrageenan gel with papain enzyme. Journal of Physics: Conference Series. 2021;1943:012175.
GLAHN, J.; et al. Evaluation of papain–urea for enzymatic debridement of coagulation zones following ablative fractional laser treatment. Lasers in Surgery and Medicine. 2024;57(2):112-120.
HAFID, K.; et al. One-step recovery of latex papain from Carica papaya using three phase partitioning and its use as milk-clotting and meat-tenderizing agent. International Journal of Biological Macromolecules. 2020;146:798-810.
KHONGLA, S.; et al. Semi-pilot scale enzymatic hydrolysis of plant proteins: Structural rearrangement and antioxidant activity optimization. Process Biochemistry. 2026;162:45-56.
MAI, N. Investigation of crosslinked hydrogel comprising papain for lesion recovery acceleration. Journal of Science and Technology. 2024;14(2):85-94.
NAYAK, K.; GUPTA, P. Study of the keratin-based therapeutic dermal patches for the delivery of bioactive molecules for wound treatment. Materials Science and Engineering: C. 2017;77:1088-1097.
NGUYEN, H. M.; et al. Biomedical materials for wound dressing: Recent advances and applications. RSC Advances. 2023;13(35):24330-24342.
PORSANI, M.; et al. Uso de gel creme de papaína na cicatrização de feridas em cães: relato de três casos. Arquivo Brasileiro de Medicina Veterinária e Zootecnia. 2016;68(5):1201-1206.
ROCHA, M.; et al. A sustainable affinity partitioning process to recover papain from Carica papaya latex using alginate as macro-ligand. Separation and Purification Technology. 2016;168:168-176.
RODRIGUES, A.; et al. Effectiveness of papain gel in venous ulcer treatment: Randomized clinical trial. Revista Latino-Americana de Enfermagem. 2015;23(3):458-465.
SALEHI, S.; et al. Clinical value of debriding enzymes as an adjunct to standard early surgical excision in human burns: A systematic review. Journal of Burn Care & Research. 2020;41(4):876-883.
SANTOS, C.; et al. Delayed tooth replantation after root surface treatment with papain and sodium fluoride in rats: A histological and histomorphometrical evaluation. Iranian Endodontic Journal. 2020;15(3):140-146.
SANTOS, T.; et al. Development and clinical application of hydrogel formulations containing papain and urea for wound healing. Brazilian Journal of Pharmaceutical Sciences. 2023;59:e20109.
SHAHEEN, S.; GALANAKIS, C.; FARAG, M. Carica papaya biowaste valorization: Biorefinery advances and extraction optimization. Food Reviews International. 2022;39(8):4745-4760.
SILVA, F. M.; et al. Curcumin and papain-loaded liposomal natural latex dressings with phototherapy: A synergistic approach to diabetic wound healing. Pharmaceuticals. 2025;18(7):1067.
SILVA MELO, A. E. C.; et al. Immobilization of papain in chitosan membranes as a potential alternative for skin wounds. Pharmaceutics. 2023;15(12):2649.
SINGLA, M.; SIT, N. Isolation of papain from ripe papaya peel using aqueous two-phase extraction. Journal of Food Measurement and Characterization. 2022;17(2):1685-1692.
SRUTHI, R. In vitro cell cytotoxicity and wound healing activity of topical film forming hydrogel of papain urea in Vero cells. YMER Digital. 2022;21(2):34-45.
STREMNITZER, C.; et al. Papain degrades tight junction proteins of human keratinocytes in vitro and sensitizes C57BL/6 mice via the skin independent of its enzymatic activity or TLR4 activation. The Journal of Investigative Dermatology. 2015;135(7):1790-1800.
TACIAS-PASCACIO, V. G.; et al. Immobilization of papain: A review. International Journal of Biological Macromolecules. 2021;188:94-113.
VASCONCELOS, N.; et al. Oxidized bacterial cellulose membranes immobilized with papain for dressing applications: Physicochemical and in vitro biological properties. Pharmaceutics. 2024;16(8):1085.
VIJAYAKUMAR, G.; et al. Comparison of efficacy of topical Carica papaya leaf extract and hemocoagulase in postoperative wound healing after therapeutic orthodontic premolar extractions: A split mouth study. Cureus. 2024;16(6):e61946.
XUE, Y.; et al. Poly (γ-glutamic acid)/chitooligo-saccharide/papain hydrogel prevents hypertrophic scar during skin wound healing. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2021;109(8):1234-1245.
YU, L.; ZHANG, H. Separation and purification of papain crude extract from papaya latex using quaternary ammonium ionic liquids as adjuvants in PEG-based aqueous two-phase systems. Food Analytical Methods. 2020;13(7):1462-1474.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Autores concordam com os seguintes termos:
a) Os autores mantêm os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a LicençaAttribution-NonCommercial-ShareAlike 4.0 International, que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial na Revista SAS. A licença permite o uso, a distribuição e a reprodução irrestrita, em qualquer meio, desde que devidamente citada a fonte. Essa licença permite também que outros remixem, adaptem e criem a partir do seu trabalho para fins não comerciais, desde que atribuam a você o devido crédito e que licenciem as novas criações sob termos idênticos.
b) Não cabe aos autores compensação financeira a qualquer título, por artigos ou resenhas publicados na South American Sciences.
c) Os conceitos expressos nos artigos publicados na South American Sciences são de inteira responsabilidade de seus autores.
