Tehnike mikroinkapsulacije za kanabinoide: farmaceutski pristupi, tehnološki izazovi i perspektive formulacije
Sažetak
Mikroinkapsulacija predstavlja široko primenjivanu strategiju za zaštitu bioaktivnih jedinjenja njihovim inkapsuliranjem u polimerni ili lipidni omotač, što vodi ka poboljšanju njihove stabilnosti i omogućava kontrolisano oslobađanje. Poslednjih godina, rastuća primena kanabinoida u proizvodima podstakla je povećano interesovanje za mikroinkapsulaciju kao pristup za prevazilaženje izazova povezanih sa njihovom niskom rastvorljivošću u vodi, hemijskom nestabilnošću i ograničenom bioraspoloživošću. Cilj ovog preglednog rada je kritička analiza i evaluacija najčešće korišćenih tehnika mikroinkapsulacije u sistemima za isporuku kanabinoida. Sistematska pretraga literature sprovedena je u bazama podataka PubMed, SCOPUS, EBSCO i Embase, pri čemu je identifikovano oko 50 originalnih i preglednih naučnih radova. Strategija pretrage obuhvatala je kombinacije ključnih reči: cannabis AND microencapsulation methods, cannabinoids AND microencapsulation techniques, hempseed oil AND spray-drying OR coacervation technology, i cannabis industry AND microencapsulation.
Rezultati ukazuju da najčešće ispitivane tehnike mikroinkapsulacije kanabinoida uključuju hlađenje raspršivanjem (engl. spray-chilling), očvršćavanje raspršivanjem (engl. spray-cooling), oblaganje u fluidizovanom sloju, lipozomsku inkapsulaciju, ekstruziju, liofilizaciju (engl. freeze-drying), koacervaciju i emulzifikaciju. Ove tehnike se razlikuju u pogledu efikasnosti inkapsulacije, skalabilnosti, raspodele veličine čestica i pogodnosti za specifične puteve primene. U celini, mikroinkapsulacija pokazuje značajan potencijal u unapređenju fizičko-hemijske stabilnosti kanabinoida, njihovoj zaštiti od degradacije izazvane spoljašnjim faktorima i omogućavanju kontrolisanog ili ciljanog oslobađanja. Zaključno, mikroinkapsulacija predstavlja obećavajuću i brzo razvijajuću strategiju u razvoju naprednih formulacija kanabinoida, nudeći inovativna rešenja za poboljšanu stabilnost, efikasniju isporuku i širu terapijsku primenu.
Reference
Chitra Devi V, Susithraa D, Abhinayasree N, Asfaque M, Sathish R, Mothil S. Microencapsulation techniques: A comprehensive review. Food Feed Res. 2025;53:84. doi: 10.5937/ffr0-55787.
Akpo E, Colin C, Perrin A, Cambedouzou J, Cornu D. Encapsulation of Active Substances in Natural Polymer Coatings. Materials (Basel). 2024;17(11):2774. doi: 10.3390/ma17112774. PMID: 38894037; PMCID: PMC11173946.
Xu Y, Yan X, Zheng H, Li J, Wu X, Xu J, et al. The application of encapsulation technology in the food Industry: Classifications, recent Advances, and perspectives. Food Chem X. 2024;21:101240. doi: 10.1016/j.fochx.2024.101240.
Singh MN, Hemant KS, Ram M, Shivakumar HG. Microencapsulation: A promising technique for controlled drug delivery. Res Pharm Sci. 2010;5(2):65–77. PMID: 21589795; PMCID: PMC3093624.
Rezagholizade-shirvan A, Soltani M, Shokri S, Radfar R, Arab M, Shamloo E. Bioactive compound encapsulation: Characteristics, applications in food systems, and implications for human health. Food Chem X. 2024;24:101953. doi: 10.1016/j.fochx.2024.101953.
Mehta N, Kumar P, Verma AK, Umaraw P, Kumar Y, Malav OP, et al. Microencapsulation as a Noble Technique for the Application of Bioactive Compounds in the Food Industry: A Comprehensive Review. Appl Sci. 2022;12(3):1424. doi: 10.3390/app12031424.
Szpicer A, Bińkowska W, Stelmasiak A, Wojtasik-Kalinowska I, Czajkowska A, Mierzejewska S, et al. Innovative Microencapsulation Techniques of Bioactive Compounds: Impact on Physicochemical and Sensory Properties of Food Products and Industrial Applications. Appl Sci. 2025;15(22):11908. doi: 10.3390/app152211908.
Lobel BT, Baiocco D, Al-Sharabi M, Routh AF, Zhang Z, Cayre OJ. Current Challenges in Microcapsule Designs and Microencapsulation Processes: A Review. ACS Appl Mater Interfaces. 2024;16(31):40326–55. doi: 10.1021/acsami.4c02462. PMID: 39042830; PMCID: PMC11311140.
Lengyel M, Kállai-Szabó N, Antal V, Laki AJ, Antal I. Microparticles, Microspheres, and Microcapsules for Advanced Drug Delivery. Sci Pharm. 2019;87(3):20. doi: 10.3390/scipharm87030020.
Das Emon D, Islam S, Rahman Mazumder A, Gulzarul Aziz M, Rahman S. Recent applications of microencapsulation techniques for delivery of functional ingredient in food products: A comprehensive review. Food Chem Adv. 2025;6:100923. doi: 10.1016/j.focha.2025.100923.
Labuschagne P. Impact of wall material physicochemical characteristics on the stability of encapsulated phytochemicals: A review. Food Res Int. 2018;107:227–47. doi: 10.1016/j.foodres.2018.02.026.
Díaz-Montes E. Wall Materials for Encapsulating Bioactive Compounds via Spray-Drying: A Review. Polymers. 2023;15(12):2659. doi: 10.3390/polym15122659.
Srivastava S, Pandey VK, Dar AH, Shams R, Dash KK, Rafiq SM, et al. Effect of microencapsulation techniques on the different properties of bioactives, vitamins and minerals. Food Sci Biotechnol. 2024;33(14):3181–3198. doi: 10.1007/s10068-024-01666-1. PMID: 39328216; PMCID: PMC11422329.
Lobel BT, Baiocco D, Al-Sharabi M, Routh AF, Zhang Z, Cayre OJ. Current Challenges in Microcapsule Designs and Microencapsulation Processes: A Review. ACS Appl Mater Interfaces. 2024;16(31):40326–40355. doi: 10.1021/acsami.4c02462. PMID: 39042830; PMCID: PMC11311140.
Lili Z, Huihui S, Zibiao L, Chaobin H. Recent Advances in Complex Coacervation Design from Macromolecular Assemblies and Emerging Applications. Macromol Rapid Commun. 2020;41:e2000149. doi: 10.1002/marc.202000149.
Santos D, Maurício AC, Sencadas V, Santos JD, Fernandes MH, Gomes PS. Spray Drying: An Overview. In: Pignatello R, Musumeci T, editors. Biomaterials - Physics and Chemistry - New Edition. London: IntechOpen; 2018.
Oxley J. Spray cooling and spray chilling for food ingredient and nutraceutical encapsulation. In: Garti N, McClements DJ, editors. Encapsulation Technologies and Delivery Systems for Food Ingredients and Nutraceuticals. Cambridge: Woodhead Publishing; 2012.
Aminahmadi B, Vaes E, Willemse F, Braile D, Gomez LN, Andersen SK, et al. Experimental and Modeling-Based Approaches for Mechanistic Understanding of Pan Coating Process—A Detailed Review. Pharmaceutics. 2026;18(1):19. doi: 10.3390/pharmaceutics18010019.
Nagiat H, Prakash K, Shanta A. Solvent Evaporation Techniques as Promising Advancement in Microencapsulation. VRI-BMC. 2013;1:8–22. doi: 10.14259/bmc.v1i1.29.
Liu S, Li J, Zhang Y, Zhang X, Ding Y, Zhang W, et al. Progress in the Preparation and Applications of Microcapsules for Protective Coatings Against Corrosion. Int J Mol Sci. 2025;26(4):1473. doi: 10.3390/ijms26041473.
Choudhury N, Meghwal M, Das K. Microencapsulation: An overview on concepts, methods, properties and applications in foods. Food Front. 2021;2:426–42. doi: 10.1002/fft2.94.
Tolve R, Bianchi F, Lomuscio E, Sportiello L, Simonato B. Current Advantages in the Application of Microencapsulation in Functional Bread Development. Foods. 2022;12(1):96. doi: 10.3390/foods12010096. PMID: 36613312; PMCID: PMC9818201.
Deepak B, Kunal G, Mallinath H, Pallavi N. LYOPHILIZATION / FREEZE DRYING – A REVIEW. World J Pharm Res. 2015;4:516–43.
Kim DH, Ki M-R, Chung DY, Pack SP. Biomolecule-Based Coacervation: Mechanisms, Applications, and Future Perspectives in Biomedical and Biotechnological Fields. Biomolecules. 2025;15(6):861. doi: 10.3390/biom15060861.
Kurozawa LE, Hubinger MD. Hydrophilic food compounds encapsulation by ionic gelation. Curr Opin Food Sci. 2017;15:50–5. doi: 10.1016/j.cofs.2017.06.004.
Freitas S, Merkle HP, Gander B. Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology. J Control Release. 2005;102(2):313–32. doi: 10.1016/j.jconrel.2004.10.015.
Pidalà J, Lombardelli C, Benucci I, Esti M. Synergistic use of Spray Drying and Fluidized Bed in the microencapsulation of food ingredients. Trends Food Sci Technol. 2025;19:105323. doi: 10.1016/j.tifs.2025.105323.
How YH, Lai KW, Pui LP, In LL. Co‐extrusion and extrusion microencapsulation: Effect on microencapsulation efficiency, survivability through gastrointestinal digestion and storage. J Food Process Eng. 2022;45(3):e13985. doi: 10.1111/jfpe.13985.
Ozkan G, Franco P, De Marco I, Xiao J, Capanoglu E. A review of microencapsulation methods for food antioxidants: Principles, advantages, drawbacks and applications. Food Chem. 2019;272:494–506. doi: 10.1016/j.foodchem.2018.07.205.
Hourfane S, Mechqoq H, Bekkali AY, Rocha JM, El Aouad N. A Comprehensive Review on Cannabis sativa Ethnobotany, Phytochemistry, Molecular Docking and Biological Activities. Plants (Basel). 2023;12(6):1245. doi: 10.3390/plants12061245. PMID: 36986932; PMCID: PMC10058143.
Leinen ZJ, Mohan R, Premadasa LS, Acharya A, Mohan M, Byrareddy SN. Therapeutic Potential of Cannabis: A Comprehensive Review of Current and Future Applications. Biomedicines. 2023;11(10):2630. doi: 10.3390/biomedicines11102630. PMID: 37893004; PMCID: PMC10604755.
Radwan MM, Chandra S, Gul S, ElSohly MA. Cannabinoids, Phenolics, Terpenes and Alkaloids of Cannabis. Molecules. 2021;26(9):2774. doi: 10.3390/molecules26092774. PMID: 34066753; PMCID: PMC8125862.
Schwilke EW, Schwope DM, Karschner EL, Lowe RH, Darwin WD, Kelly DL, et al. Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC. Clin Chem. 2009;55(12):2180–9. doi: 10.1373/clinchem.2008.122119. PMID: 19833841; PMCID: PMC3196989.
Kicman A, Toczek M. The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease. Int J Mol Sci. 2020;21(18):6740. doi: 10.3390/ijms21186740. PMID: 32937917; PMCID: PMC7554803.
Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants (Basel). 2019;9(1):21. doi: 10.3390/antiox9010021. PMID: 31881765; PMCID: PMC7023045.
Lacerda M, Carona A, Castanheira S, Falcão A, Bicker J, Fortuna A. Pharmacokinetics of Non-Psychotropic Phytocannabinoids. Pharmaceutics. 2025;17(2):236. doi: 10.3390/pharmaceutics17020236.
Arnold JC, McCartney D, Suraev A, McGregor IS. The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence. Clin Transl Sci. 2023;16(1):10–30. doi: 10.1111/cts.13425. PMID: 36259271; PMCID: PMC9841308.
Sobieraj J, Strzelecka K, Sobczak M, Oledzka E. How Biodegradable Polymers Can be Effective Drug Delivery Systems for Cannabinoids? Prospectives and Challenges. Int J Nanomedicine. 2024;19:4607–49. doi: 10.2147/IJN.S458907. PMID: 38799700; PMCID: PMC11128233.
Ladha KS, Ajrawat P, Yang Y, Clarke H. Understanding the Medical Chemistry of the Cannabis Plant is Critical to Guiding Real World Clinical Evidence. Molecules. 2020;25(18):4042. doi: 10.3390/molecules25184042. PMID: 32899678; PMCID: PMC7570835.
Tănase Apetroaei V, Pricop EM, Istrati DI, Vizireanu C. Hemp Seeds (Cannabis sativa L.) as a Valuable Source of Natural Ingredients for Functional Foods-A Review. Molecules. 2024;29(9):2097. doi: 10.3390/molecules29092097. PMID: 38731588; PMCID: PMC11085560.
Kamle M, Kumar Mahato D, Sharma B, Gupta A, Kumar Shah A, Mahmud C, et al. Nutraceutical potential, phytochemistry of hemp seed (Cannabis sativa L.) and its application in food and feed: A review. Food Chem Adv. 2024;4:100671. doi: 10.1016/j.focha.2024.100671.
Hanuš LO, Hod Y. Terpenes/Terpenoids in Cannabis: Are They Important? Med Cannabis Cannabinoids. 2020;3(1):25–60. doi: 10.1159/000509733. PMID: 34676339; PMCID: PMC8489319.
Ayyagari MM, Heim D, Sumnall HR, Monk RL. Contextual factors associated with subjective effects of cannabis: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2024;164:105822. doi: 10.1016/j.neubiorev.2024.105822.
Palrasu M, Wright L, Patel M, Leech L, Branch S, Harrelson S, Khan S. Perspectives on Challenges in Cannabis Drug Delivery Systems: Where Are We? Med Cannabis Cannabinoids. 2022;5(1):102–19. doi: 10.1159/000525629. PMID: 36467783; PMCID: PMC9710325.
Paczkowska-Walendowska M, Trzaskoma P, Dziopa A, Moeini A, Soczawa M, Krasiński Z, Cielecka-Piontek J. Innovative Strategies to Enhance the Bioavailability of Cannabidiol: Nanotechnology and Advanced Delivery Systems. Pharmaceuticals (Basel). 2025;18(11):1637. doi: 10.3390/ph18111637. PMID: 41304881; PMCID: PMC12655173.
Bajtel Á, Kiss T, Tóth B, Kiss S, Hegyi P, Vörhendi N, et al. The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Pharmaceuticals (Basel). 2022;15(1):100. doi: 10.3390/ph15010100. PMID: 35056154; PMCID: PMC8778752.
O'Donnell B, Meissner H, Gupta V. Dronabinol. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2025 [cited 2026 Feb 16]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557531/.
Cesamet (nabilone) capsules [Internet]. U.S. Food and Drug Administration; 2006 [cited 2026 Feb 16]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018677s011lbl.pdf.
United Nations Office on Drugs and Crime. Single Convention on Narcotic Drugs. 1961.
Stella B, Baratta F, Della Pepa C, Arpicco S, Gastaldi D, Dosio F. Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain. Drugs. 2021;81(13):1513–1557. doi: 10.1007/s40265-021-01579-x. PMID: 34480749; PMCID: PMC8417625.
Wang C, Cui B, Sun Y, Wang C, Guo M. Preparation, stability, antioxidative property and in vitro release of cannabidiol (CBD) in zein-whey protein composite nanoparticles. LWT. 2022;162:113466. doi: 10.1016/j.lwt.2022.113466.
Villate A, San Nicolas M, Olivares M, Aizpurua-Olaizola O, Usobiaga A. Chitosan-Coated Alginate Microcapsules of a Full-Spectrum Cannabis Extract: Characterization, Long-Term Stability and In Vitro Bioaccessibility. Pharmaceutics. 2023;15(3):859. doi: 10.3390/pharmaceutics15030859.
Phupaboon S, Matra M, Prommachart R, Totakul P, Supapong C, Wanapat M. Extraction, Characterization, and Chitosan Microencapsulation of Bioactive Compounds from Cannabis sativa L., Cannabis indica L., and Mitragyna speiosa K. Antioxidants. 2022;11(11):2103. doi: 10.3390/antiox11112103.
Kurek MA, Pratap-Singh A. Plant-Based (Hemp, Pea and Rice) Protein–Maltodextrin Combinations as Wall Material for Spray-Drying Microencapsulation of Hempseed (Cannabis sativa) Oil. Foods. 2020;9(11):1707. doi: 10.3390/foods9111707.
Lan Y, Ohm JB, Chen B, Rao J. Microencapsulation of hemp seed oil by pea protein isolate−sugar beet pectin complex coacervation: Influence of coacervation pH and wall/core ratio. Food Hydrocoll. 2021;113:106423. doi: 10.1016/j.foodhyd.2020.106423.
Majimbi M, Brook E, Galettis P, Eden E, Al-Salami H, Mooranian A, et al. Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid. PLoS One. 2021;16(6):e0243858. doi: 10.1371/journal.pone.0243858.
Zhang Q, Shi Y, Tu Z, Hu Y, He C. Emulsion Properties during Microencapsulation of Cannabis Oil Based on Protein and Sucrose Esters as Emulsifiers: Stability and Rheological Behavior. Foods. 2022;11(23):3923. doi: 10.3390/foods11233923. PMID: 36496731; PMCID: PMC9735479.
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