Alginate-Based Encapsulation Fabrication Technique for Drug Delivery: An Updated Review of Particle Type, Formulation Technique, Pharmaceutical Ingredient, and Targeted Delivery System
Abstract
:1. Introduction
2. Applications of Alginate
2.1. Alginates in the Market
2.2. Application of Alginate in the Drug Delivery System
3. Microspheres and Nanoparticles
4. Microcapsules and Microbeads
5. Microgels, Micelles, and Nanofibers
6. Composite and Scaffold Systems
7. Future Directions and Challenges
8. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Alginate Type | Applications | Advantages | Disadvantages |
---|---|---|---|
High-G alginates | Dental impressions, 3D printing, tissue engineering | Strong rigid gels, high stability, excellent printability | Brittle gels, low biocompatibility |
High-M alginates | Food gels, biomedical hydrogels | Soft elastic gels, good biocompatibility | Weak gels, low stability |
High-MG alginates | Thickeners, encapsulation | Cohesive gels, viscosity enhancement | Intermediate strength and stability |
Modified alginates | Cosmetics, coatings, specialized delivery | Enhanced stability, adhesion, moisture retention | Can lose intrinsic properties of natural alginate |
Product | Manufacturer | Use | Alginate Type |
---|---|---|---|
NovaMatrix | FMC BioPolymer | Pharmaceutical excipient for oral drug delivery | High-G sodium alginate |
Kaltostat | ConvaTec | Wound dressing with hemostatic properties | Calcium alginate |
Gaviscon | Reckitt | Antacid formulation | Sodium alginate |
Types of Particle | Formulation Technique | Active Pharmaceutical Ingredient | Concentration of Alginate | Target System | Findings | Reference |
---|---|---|---|---|---|---|
Microsphere | Freeze drying | Metformin | - | Intestine | Controlled drug release in gastric conditions and sustained drug release in intestinal conditions are achieved with this formulation. This notwithstanding, the therapeutic effect of metformin is also enhanced. Therefore, this formulation is deemed as a potential approach to deliver metformin for a prolonged duration of action. | Maestrelli et al., [37] |
Microparticle | Ionotropic gelation | Curcumin | 0.63 mg/mL | Topical | The fabricated microparticles were shown to have an enhanced wound healing effect with a drug encapsulation efficiency of 75%. Moreover, a sustained drug release mechanism is also achieved with this alginate-based formulation, hence proving the potential use of this biodegradable formulation to deliver curcumin topically. | Shahnia, [38] |
Nanoparticle | Co-precipitation approach | Curcumin | 40% | GIT | This alginate formulation exhibits an excellent sustained drug release profile in a pH-sensitive manner. A prolonged duration of action of the drug is also observed. With its good encapsulation efficiency and the drug release profile, it is indicated as one of the potential methods to achieve targeted drug delivery. | Manatunga et al., [39] |
Microsphere | Cross-linking and ionotropic gelation | Selenium | 1.5% w/w | Intestine | Minimal drug release in gastric conditions is observed with this formulation, while the release duration and duration of action in intestinal conditions are prolonged, hence indicating a pH-sensitive drug release profile. Therefore, this alginate-based formulation is deemed as one of the potential approaches to deliver selenium in the intestine. | Cavalu et al., [40] |
Microcapsule | Complex coacervation | Buriti oil | 1% w/w | - | Encapsulation efficiency of approximately 80% is achieved with this formulation. | Lemos et al., [41] |
Nanoparticle | Emulsification and cross-linking process | Curcumin | 0.6 mg/mL | Prostate | Slow drug release and high cellular uptake of curcumin are demonstrated with this formulation. Moreover, curcumin’s cytotoxic action towards prostate cancer cells is also observed with the absence of hemolysis after the administration, proving its safety for human use. | Saralkar & Dash, [42] |
Nanoparticle | Freeze drying | 5-fluorouracil | 2.5% w/v | Intestine (Colon) | This alginate-based formulation exhibits a colon-targeted drug release profile with a reduced drug toxicity. Therefore, it is deemed as a potential approach to deliver the drug for a colon-targeted treatment. | Zhang et al., [43] |
Microcapsule | Layer-by-layer (LbL) technique | Doxorubicin | - | Breast | This formulation revealed a better cellular uptake and cytotoxic action against the breast cancer cells as compared with the free drug. Prolonged retention time in targeted areas has also been demonstrated. Therefore, it is deemed as a significant drug delivery method for treating drug-resistant breast cancer. | Shen et al., [44] |
Nanoparticle | Co-precipitation OR layer-by-layer coating | Curcumin | 20 mg/mL | Breast | This alginate-based formulation has demonstrated a sustained drug release profile, along with an enhanced cellular uptake efficiency, as compared to the free drug. Its cytotoxic effect against cancer cells is also improved. Hence, it is one of the most promising approaches to deliver the drug for cancer treatment. | Song et al., [45] |
Nanogel | Cross-linking/emulsification | 5-Fluorouracil | 1.8% w/w | Intestine (Colon) | The prepared hydrogels are found to be cytocompatible with an encapsulation efficiency of up to 82%, where the drugs are able to be released under conditions that are similar to intravascular pressure. In addition, this formulation can also be rapidly uptaken by the colon cell line with high cellular accumulation as compared to the free drug. Therefore, it is considered as a promising approach to deliver the drug for colon cancer therapy. | Hosseinifar et al., [46] |
Microparticle | Ionotropic gelation (coacervation) technique | Vancomycin | 1–2% w/v | Intestine | A controlled drug release profile with an average release rate of 22 μg/d for 2 weeks is observed in this formulation. | Unagolla and Jayasuriya, [47] |
Microcapsule | Complex coacervation technique | Astaxanthin oleoresin | 0.5% w/v | Intestine | The fabricated microcapsules have shown a good encapsulation efficiency of up to 85.9%. In addition, the stability of the active ingredient against the heat, oxygen, and light is improved too, subsequently improving its bioavailability. A controlled drug release is demonstrated in intestinal conditions, where a rapid release of the drug is observed under an alkaline environment, proving that the coating material is able to resist the acidic conditions. | Li et al., [48] |
Microgel sphere | - | Green tea polyphenol | 2% | Bone | A controlled drug release is achieved with this formulation in a pH-sensitive manner. High trapping efficiency of approximately 92% is also observed. | Chen et al., [49] |
Microparticle | Ionotropic gelation method | Ibuprofen | 1–2.8% w/v | GIT | This study has proved that with high alginate content, sustained drug release profile and better drug encapsulation will be achieved. | Freitas et al., [35] |
Nanoparticle | O/W emulsification and ionotropic gelification | Curcumin diglutaric acid | 0.6 mg/mL | Intestine (Colon), liver, and breast | Stability under UV radiation and in the simulated gastrointestinal environment is improved with this formulation. In addition, a delayed cumulative drug release in GIT condition is achieved. Cellular uptake by colon, liver, and breast cancer cells is also improved, as well as its anti-cancer effects. Hence, it is deemed as a potential method to deliver drugs for cancer therapy. | Sorasitthiyanukarn et al., [33] |
Micelle | - | Curcumin | - | - | A controlled drug release profile is observed for a prolonged period of up to 5 h under physiological conditions. Its safety for human use has been confirmed by the absence of aggregation and hemolysis of red blood cells after administration. It is also found that it can be rapidly uptaken by the cell, in which the highest concentration was observed within 1 h after the treatment. Hence, it is deemed as a safe and efficient drug delivery system for curcumin. | Lachowicz et al., [50] |
Microencapsulated matrix/nanofibrous scaffold | Freeze gelation | Curcumin | - | Topical (Wound) | Excellent anti-cancer activity against cancer cells on both normal and human lung adenocarcinoma cells is observed. This formulation is also found to be stable against enzymatic degradation. | Gnanamangai et al., [51] |
Microcapsule | - | Stellaria media | 2% w/v | GIT | A good encapsulation efficiency of up to 92.47% is achieved with this formulation. Controlled drug release mechanism is also observed, where a major portion of the drug is released in intestinal conditions rather than gastric conditions. | Miere et al., [52] |
Nanomicelle/microsphere | - | Dasatinib and zein-lactoferrin | - | Breast | Sustained drug release profile is achieved with this formulation. The fabricated formulation also showed excellent cytotoxic action against the breast cancer cell line. This notwithstanding, this alginate-based formulation also demonstrated a significant encapsulation efficiency. | Ragab et al., [53] |
Nanoparticle | Ionotropic gelation technique | Curcumin | 1% | Intestine (Colon) | An improved encapsulation efficiency of up to 95% is observed with this formulation. This formulation also demonstrated an extremely low dissolution rate in GIT conditions, in which the major portion of the drug is released in colon conditions. Additionally, the drug bioavailability is also shown to be enhanced by 5 times after the encapsulation. | Govindaraju et al., [54] |
Nanoparticle | Ionic gelation technique | Curcumin | 0.025% w/v | - | Drug loading efficiency up to 90% is observed with this formulation, with a sustained drug release profile. | Pornpitchanarong et al., [55] |
Sponge (wound dressing) | Freeze-drying | Curcumin | 1% | Topical | This formulation is shown to be able to facilitate the wound healing process by improving the drug release and water uptake profiles. | Zhao et al., [56] |
Nanoparticle/wound dressing | Emulsification–diffusion method | Curcumin | 4% w/v | Topical | High mechanical strength with good absorbency ability are achieved with this formulation. Additionally, controlled drug release profiles with delayed degradation are also observed. | Guadarrama-Acevedo et al., [57] |
Nanoparticle | Ionic gelation method | Rifampicin | 0.06% w/v | Pulmonary route | Improved therapeutic efficacy is revealed with this formulation, mainly owing to its improved redispersibility in water. Drug concentration in the targeted area is also increased, while the systemic toxicity of the drug is reduced. Therefore, it is deemed as a potential method to deliver the drug through a pulmonary route. | Scolari et al., [34] |
Microparticle | Spray drying | Curcumin | 1% w/v | - | A slow drug release is observed with this formulation. In addition, encapsulation efficiency up to 97.6% is also achieved. | Lucas et al., [58] |
Biopolymer composite film | Mechanical blending and casting method | Curcumin | - | Topical | The prepared formulation exhibits a potent anti-cancer effect towards the oral cancer cells, whilst its mucoadhesion time for porcine mucosa is observed as 30 to 36 min under the artificial saliva conditions. | Chiaoprakobkij et al., [59] |
Microfiber | Ionotropic gelation method | Curcumin | 10–100% | Topical | A prolonged drug release is observed with this formulation for up to 85% in 3 d. Owing to its significant effect on wound healing, this formulation is indicated as a potential approach for wound management. | Sharma et al., [60] |
Nanogel | Cross-linking process | Oxaliplatin | - | Intestine (Colorectal) | Improved anti-cancer activity towards the colorectal adenocarcinoma cell line is seen with this formulation. Therefore, it is considered as a significant approach to deliver oxaliplatin for colorectal cancer treatment. | Shad et al., [61] |
Microsphere | Spray drying | Ropinirole hydrochloride | 0.5% w/v | Nasal epithelium | Excellent stability profile and high drug trapping efficiency, up to 106%, are observed with this formulation. | Hussein et al., [62] |
Nanosphere | Ionotropic gelification | Curcumin | - | Breast | Great drug encapsulation efficiency and delayed drug release up to 24 h are observed. Curcumin’s absorption is also improved. After the administration, the proliferation of the breast cancer cells is significantly reduced. | Afzali et al., [63] |
Microbead | In situ ion-exchange followed by simple ionotropic gelation technique | Curcumin | - | Intestine | Extended release of curcumin is revealed with this alginate-based formulation, subsequently improving its bioavailability and anti-tumor effect. | Sreekanth Reddy et al., [5] |
Microparticle | Ionic gelation/ eudragit S 100 coating | Cyclosporine A | - | Intestine (Colon) | This formulation has achieved a good drug encapsulation efficiency of approximately 77%. During the study, it has been found that the drug release was inhibited under stomach and small intestine conditions, whilst under a simulated colon environment, a drug dissolution followed by a sustained drug release is achieved, hence minimizing the systemic absorption and side effects. Hence, it is considered as a promising approach to deliver the drug for the treatment of ulcerative colitis. | Oshi et al., [36] |
Nanoparticle/scaffold | - | Curcumin | 2% | Topical | A good drug encapsulation profile is achieved with this formulation. | Mobaraki et al., [64] |
Hydrogel bead | Ionotropic gelation method | Curcumin | 2% | GIT | Controlled drug release is achieved with this formulation under simulated GI conditions. | Sharma et al., [65] |
Nanoparticle | - | Curcumin | 1% w/v | Intestine (Colon) | A good drug encapsulation efficiency up to 91% is observed in this study. Moreover, it is also found that the drug absorption by the colon cancer cells is improved with the prepared formulation, as compared to the free drug, subsequently improving its target efficiency. Therefore, this alginate-based formulation is indicated as one of the most promising approaches for treating colon cancer. | Liu et al., [66] |
Hydrogel | Ionic gelation technique | Curcumin | - | Lung and breast | A better anti-cancer effect is proved with this formulation. | Torbati et al., [67] |
Microsphere | Complex coacervation technique | Quercetin | 0.75% v.v | GIT | High drug trapping efficiency of approximately 86% is achieved, as well as the controlled release of drugs. This notwithstanding, it is found that the thermal stability of the drug is enhanced with this formulation and, owing to the lipophobicity of the matrix, quercetin is protected from the enzymatic degradation in the GIT. | Frenț et al., [68] |
Microsphere/microbead | Emulsion-templated ionic gelation | Curcumin/5-FU | 3% | Breast | A pH-sensitive drug delivery system is revealed in this study. Moreover, the anti-cancer activity of the drugs are also improved. | Boddu et al., [69] |
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Lai, J.; Azad, A.K.; Sulaiman, W.M.A.W.; Kumarasamy, V.; Subramaniyan, V.; Alshehade, S.A. Alginate-Based Encapsulation Fabrication Technique for Drug Delivery: An Updated Review of Particle Type, Formulation Technique, Pharmaceutical Ingredient, and Targeted Delivery System. Pharmaceutics 2024, 16, 370. https://doi.org/10.3390/pharmaceutics16030370
Lai J, Azad AK, Sulaiman WMAW, Kumarasamy V, Subramaniyan V, Alshehade SA. Alginate-Based Encapsulation Fabrication Technique for Drug Delivery: An Updated Review of Particle Type, Formulation Technique, Pharmaceutical Ingredient, and Targeted Delivery System. Pharmaceutics. 2024; 16(3):370. https://doi.org/10.3390/pharmaceutics16030370
Chicago/Turabian StyleLai, Joanne, Abul Kalam Azad, Wan Mohd Azizi Wan Sulaiman, Vinoth Kumarasamy, Vetriselvan Subramaniyan, and Salah Abdalrazak Alshehade. 2024. "Alginate-Based Encapsulation Fabrication Technique for Drug Delivery: An Updated Review of Particle Type, Formulation Technique, Pharmaceutical Ingredient, and Targeted Delivery System" Pharmaceutics 16, no. 3: 370. https://doi.org/10.3390/pharmaceutics16030370
APA StyleLai, J., Azad, A. K., Sulaiman, W. M. A. W., Kumarasamy, V., Subramaniyan, V., & Alshehade, S. A. (2024). Alginate-Based Encapsulation Fabrication Technique for Drug Delivery: An Updated Review of Particle Type, Formulation Technique, Pharmaceutical Ingredient, and Targeted Delivery System. Pharmaceutics, 16(3), 370. https://doi.org/10.3390/pharmaceutics16030370