Recent Fabrication Methods to Produce Polymer-Based Drug Delivery Matrices (Experimental and In Silico Approaches)
Abstract
:1. Introduction
2. Micro- and Nano-Technologies
2.1. Micro- and Nano-Particles
2.2. Polymeric Layered Secondary Oil-in-Water Nanoemulsions
2.3. Different Methods for Polymeric Micro and Nanoparticles Synthesis
2.3.1. Nanoemulsion Assembly
- oil phase (as corn oil, soybean oil, olive oil, peanut oil, and flaxseed oil with short or medium chain length, which are harmless to the human body) [58]
- water phase (generally water)
- surfactants (emulsifier agents, such as non-ionic surfactant, e.g., lecithin, poloxamers, or non-electrolytes, such as glycerol or xylitol [59] or food-grade emulsifiers, such as β-lactoglobulin, whey protein isolate and octenyl succinic acid modified starch, gum Arabic acid and other polysaccharides) [58]
- co-surfactants (short chain alcohol, organic ammonia, single and double amino acid glyceride and the most used is short chain alcohol, commonly used to aid the emulsifier has ethanol, ethylene glycol, propylene glycol, propylene triol, and poly glyceride) [60].
2.3.2. Emulsion Solvent Evaporation Method
2.3.3. Single Emulsion Technique
2.3.4. Double Emulsion
2.3.5. Emulsification/Solvent Diffusion
2.3.6. Salting-Out
2.3.7. Nanoprecipitation
2.4. Microfluidics
2.4.1. Flow Focusing
2.4.2. T-Junction
2.4.3. Coaxial-Flow
2.5. Microneedles
2.6. Polymer Fibers by Electrospinning
3. In Silico Models
- Geometry: such as, length, height, radium, and the thickness of the membrane. The main geometric parameters are shown in Figure 8;
- Material exploited to realize the devices for drug delivery: such as polymer molecular weight, viscosity, degree of crystallinity, parameters related to the interactions between polymer and solvent (e.g., surface erosion rate constant [151], and temperature), or to the polymer swelling and dissolution;
4. Different Approaches for Mathematical Modelling
4.1. Mechanistic Realistic Theories
- Diffusion: the drug release is controlled by the diffusion processes (Figure 9a). For this type of model, the initial conditions are represented by the concentration of the drug at the beginning of the release processes, while the boundary conditions are assumed for surface, mass, and volume of the surrounding medium. It is possible to distinguish between reservoir, monolithic, and miscellaneous systems, based on the strategy employed to deliver the drug, each of which with specific initial and boundary conditions [22,147,151,156].
- Swelling: this mechanism allows better control of the release of a specific drug. There are two important consequences of the polymer swelling, which concern the increment of the diffusive path due to the decrease of the concentration gradient, and, increment of the mobility of the macromolecules with an improvement of the drug release (Figure 9b) [147,157].
4.2. Empirical/Semiempirical Theories
5. In-Silico Methods to Assess the Performance and Design of Polymer-Based Drug Delivery Systems
6. Polymer-Based Micro and Nano Matrices for Drug Delivery on Market
6.1. Polymeric Nanoparticles
6.2. In Situ Gelling Systems
6.3. Implants
6.4. Polymer Microneedles
6.5. Electrospinning Based Nanofibers
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Morphology | Polymer | Payload | Method | Indication | References |
---|---|---|---|---|---|
Nanostructure | chitosan layered | coenzyme Q10 | oil in water nanoemulsions | anti-inflammatory effects | [44] |
Nanostructure | chitosan layered | lycopene | oil in water nanoemulsions | cardioprotective effects | [46] |
Nanostructure | chitosan layered | curcumin | oil in water nanoemulsions | anti-inflammatory | [48] |
Nanostructure | PLGA | noscapine | oil in water nanoemulsions | anticancer | [65] |
Nanostructure | PLGA | turmeric | emulsion-solvent evaporation | antioxidant activity | [66] |
Nanostructure | polyallylamine | clindamycin | salting out | osteomyelitis treatment | [82] |
Nanostructure | mPEG–PTMC | dexamethasone | salting out/double emulsion | anti-inflammatory | [83] |
Nanostructure | PLA | Savoxepine | salting-out | neuroleptics effect | [84] |
Nanostructure | PEG-b-PCL | aza-BODIPY | nanoprecipitation | cancer treatment | [85] |
Microstructure | PLGA-PEG | clofazimine | nanoprecipitation | tuberculosis | [86] |
Microstructure | alginate | probiotic L. paracasei CBA L74 | water-in-oil emulsion technique | microbiota disfunction | [8] |
Microstructure | PLGA | collagenase | water in oil in water | skin pathologies | [25] |
Microstructure | PLGA | donepezil | oil in water emulsion | Alzheimer treatment | [64] |
Microstructure | PLGA | vascular endothelial growth factor | water in oil in water | angiogenic effect | [26] |
Microstructure | PLGA | laccase | water in oil in water | Cosmetic | [27] |
PLGA wt % | PLGA Flow Rate * μL/min | AP Flow Rate μL/min | Outer Droplet Size μm | Picture ** | Final Bead Size μm | Picture ** |
---|---|---|---|---|---|---|
2 | 5 (11.6) | 70 | 57.2 | | 28.7 | |
2 (2.6) | 57.7 | | 25.6 | | ||
2 (2.6) | 30 | 67.4 | | 29.9 | | |
6 | 5 (10.1) | 70 | 61.6 | | 36.9 | |
2 (2.3) | 58.4 | | 36.7 | | ||
2 (2.3) | 30 | 74.9 | | 45.4 | | |
5 (10.1) | 30 | 72.2 | | 45.4 | |
Type | Trade Name | Formulation | Indication |
---|---|---|---|
Polymeric Nanoparticles | Lupron Depot | microspheres composed of PLA-PLGA copolymer and leuprolide acetate | prostate cancer |
Sculptra | PLA microparticles | facial lipoatrophy, facial wrinkles | |
Zilretta | triamcinolone acetonide embedded in a PLGA hydrogel | knee osteoarthritis | |
Bydureon BCise | exenatide sustained-release | type 2 diabetes | |
Adagen | PEGylated adenosine deaminase enzyme | immunodeficiency disease | |
Cimzia | PEGylated antibody fragment | rheumatoid/psoriatic arthritis | |
Neulasta | PEGylated form of filgrastim | Neutropenia | |
Plegridy | PEG-IFN-β-1a | multiple sclerosis | |
Gelling systems | Eligard | leuprolide acetate and polymer PLGA | prostate cancer |
Zoladex | goserelin acetate dispersed in a cylindrical PLGA matrix | prostate cancer and endometriosis | |
OncoGel | paclitaxel and a PLGA-PEG thermosensitive polymer system | solid tumors | |
Implants | Retisert | fluocinolone acetonide in a tablet reservoir | noninfectious uveitis |
Vitrasert | ganciclovir tablet reservoir | cytomegalovirus retinitis | |
Ozurdex | dexamethasone sustained-release implant | macular edema and noninfectious uveitis | |
Polymeric Microneedles | V-Go | TOPAS cyclic olefin copolymer | type 2 diabetes |
Sanofi’s Fluzone Intradermal Quadrivalent | n.d. | influenza A subtype viruses and type B viruses | |
Electrospinning based nanofibers | Rivelin | muco-adhesive two layered patch | mucosal diseases |
SurgiClot | fibrin sealant patch | bone bleeding |
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Procopio, A.; Lagreca, E.; Jamaledin, R.; La Manna, S.; Corrado, B.; Di Natale, C.; Onesto, V. Recent Fabrication Methods to Produce Polymer-Based Drug Delivery Matrices (Experimental and In Silico Approaches). Pharmaceutics 2022, 14, 872. https://doi.org/10.3390/pharmaceutics14040872
Procopio A, Lagreca E, Jamaledin R, La Manna S, Corrado B, Di Natale C, Onesto V. Recent Fabrication Methods to Produce Polymer-Based Drug Delivery Matrices (Experimental and In Silico Approaches). Pharmaceutics. 2022; 14(4):872. https://doi.org/10.3390/pharmaceutics14040872
Chicago/Turabian StyleProcopio, Anna, Elena Lagreca, Rezvan Jamaledin, Sara La Manna, Brunella Corrado, Concetta Di Natale, and Valentina Onesto. 2022. "Recent Fabrication Methods to Produce Polymer-Based Drug Delivery Matrices (Experimental and In Silico Approaches)" Pharmaceutics 14, no. 4: 872. https://doi.org/10.3390/pharmaceutics14040872
APA StyleProcopio, A., Lagreca, E., Jamaledin, R., La Manna, S., Corrado, B., Di Natale, C., & Onesto, V. (2022). Recent Fabrication Methods to Produce Polymer-Based Drug Delivery Matrices (Experimental and In Silico Approaches). Pharmaceutics, 14(4), 872. https://doi.org/10.3390/pharmaceutics14040872