Optimization of Polylactide-Co-Glycolide-Rifampicin Nanoparticle Synthesis, In Vitro Study of Mucoadhesion and Drug Release
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Rifampicin Loaded PLGA Nanoparticles
2.3. Experimental Design of Central Composite Design
2.4. Measurement of Particle Size, Polydispersity and Zeta Potential
2.5. Determination of Drug Loading Efficiency and Nanoparticle Yield
2.6. In Vitro Release of Drug from Polymer Nanoparticles
2.7. Thermogravimetric Analysis and Differential Scanning Calorimetry
2.8. Study of Prepared Nanoparticles by Infrared Spectroscopy
2.9. In Vitro Study of Nanoparticle Mucoadhesion
2.10. Statistical Processing of the Produced Data
3. Results and Discussion
3.1. Synthesis and Optimization of Conditions for Producing PLGA-RIF NPs
3.2. Physicochemical Characterization of PLGA-RIF Nanoparticles
3.3. In Vitro Release Profile of PLGA-RIF NPs
3.4. In Vitro Mucoadhesion of PLGA-RIF NPs
3.5. In Vitro Efficacy of PLGA-RIF NPs against Strain H37Rv
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Independent Variable | Variable Level | ||
---|---|---|---|
Low –1 | Center 0 | High 1 | |
PLGA:RIF | 1:1 | 2:1 | 3:1 |
MW of PLGA | 7000–17,000 | 24,000–38,000 | 30,000–60,000 |
Surfactant | PVA | Tween 80 | Pluronic F127 |
Concentration of surfactant | 0.5% | 1% | 2% |
Organic solvent | DCM | DMSO | EA |
Organic phase: aqueous phase | 1:1 | 1:5 | 1:10 |
Homogenization power | 15 W | 35 W | 70 W |
Homogenization time | 5 min | 10 min | 15 min |
NPs | PLGA:RIF Ratio | MW PLGA | Surfactant | Surfactant Concentration, % | Organic Solvent | Organic Phase:Aqueous Phase | Homogenization Power, W | Homogenization Time, min | Average Size, nm | PDI | Zeta Potential, mV | LE, % | NPs Yield, % |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 |
NP1 | 3:1 | PLGA30 | PVA | 0.5 | EA | 1:1 | 15 | 5 | 189 ± 2 | 0.046 ± 0.003 | −30.9 ± 3.4 | 58 | 75 |
NP2 | 3:1 | PLGA30 | PVA | 2 | DCM | 1:1 | 15 | 5 | 422 ± 2 | 0.280 ± 0.013 | −13.1 ± 1.8 | 64 | 59 |
NP3 | 3:1 | PLGA7 | Pluronic F127 | 2 | EA | 1:10 | 15 | 5 | 316 ± 2 | 0.349 ± 0.051 | −28.2 ± 3.3 | 24 | 22 |
NP4 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 220 ± 2 | 0.177 ± 0.023 | −20.1 ± 0.6 | 45 | 33 |
NP5 | 3:1 | PLGA7 | Pluronic F127 | 2 | EA | 1:1 | 70 | 5 | 94 ± 1 | 0.285 ± 0.067 | −22.8 ± 2.3 | 88 | 26 |
NP6 | 1:1 | PLGA7 | PVA | 0.5 | EA | 1:1 | 70 | 15 | 219 ± 2 | 0.489 ± 0.035 | −0.61 ± 2.1 | 78 | 41 |
NP7 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 15 | 175 ± 2 | 0.191 ± 0.046 | −15.6 ± 3.7 | 29 | 67 |
NP8 | 3:1 | PLGA30 | PVA | 2 | EA | 1:10 | 15 | 15 | 452 ± 3 | 0.499 ± 0.086 | −15.8 ± 2.9 | 31 | 66 |
NP9 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 170 ± 2 | 0.358 ± 0.008 | −23.2 ± 4.2 | 40 | 34 |
NP10 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 172 ± 2 | 0.178 ± 0.008 | −21.6 ± 2.8 | 37 | 37 |
NP11 | 3:1 | PLGA7 | PVA | 0.5 | DCM | 1:1 | 15 | 5 | 443 ± 3 | 0.261 ± 0.034 | −14.5 ± 3.4 | 52 | 69 |
NP12 | 1:1 | PLGA30 | Pluronic F127 | 0.5 | DCM | 1:10 | 70 | 5 | 260 ± 2 | 0.262 ± 0.045 | −24.3 ± 2.2 | 30 | 33 |
NP13 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 184 ± 2 | 0.186 ± 0.080 | −23.2 ± 2.1 | 33 | 31 |
NP14 | 3:1 | PLGA7 | Pluronic F127 | 2 | DCM | 1:10 | 70 | 5 | 219 ± 2 | 0.248 ± 0.065 | −20.3 ± 3.1 | 23 | 36 |
NP15 | 1:1 | PLGA7 | PVA | 2 | EA | 1:1 | 15 | 5 | 119 ± 2 | 0.217 ± 0.013 | −11.2 ± 2.7 | 44 | 41 |
NP16 | 1:1 | PLGA7 | Pluronic F127 | 2 | EA | 1:1 | 15 | 15 | 166 ± 3 | 0.556 ± 0.039 | −20.1 ± 1.4 | 16 | 3 |
NP17 | 3:1 | PLGA7 | PVA | 0.5 | EA | 1:10 | 70 | 5 | 356 ± 3 | 0.474 ± 0.023 | −12.8 ± 1.3 | 48 | 68 |
NP18 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:1 | 35 | 10 | 291 ± 2 | 0.373 ± 0.034 | −15.4 ± 0.3 | 37 | 55 |
NP19 | 2:1 | PLGA24 | PVA | 1 | DMSO | 1:5 | 35 | 10 | 206 ± 3 | 0.135 ± 0.023 | −13.2 ± 1.3 | 39 | 33 |
NP20 | 1:1 | PLGA30 | Pluronic F127 | 2 | DCM | 1:10 | 15 | 15 | 271 ± 1 | 0.508 ± 0.056 | −9.5 ± 1.5 | 27 | 31 |
NP21 | 1:1 | PLGA30 | PVA | 0.5 | DCM | 1:1 | 70 | 5 | 282 ± 2 | 0.145 ± 0.034 | −16.4 ± 2.3 | 65 | 61 |
NP22 | 2:1 | PLGA24 | Tween 80 | 2 | DMSO | 1:5 | 35 | 10 | 193 ± 4 | 0.224 ± 0.006 | −18.5 ± 3.3 | 40 | 28 |
NP23 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 70 | 10 | 167 ± 3 | 0.276 ± 0.013 | −15.6 ± 1.3 | 41 | 17 |
NP24 | 1:1 | PLGA7 | Pluronic F127 | 0.5 | EA | 1:1 | 15 | 5 | 94 ± 2 | 0.206 ± 0.043 | −13.9 ± 1.6 | 48 | 32 |
NP25 | 1:1 | PLGA30 | Pluronic F127 | 0.5 | EA | 1:1 | 70 | 15 | 95 ± 3 | 0.238 ± 0.023 | −20.7 ± 3.1 | 55 | 30 |
NP26 | 3:1 | PLGA7 | Pluronic F127 | 0.5 | DCM | 1:1 | 70 | 15 | 271 ± 4 | 0.116 ± 0.032 | −17.5 ± 0.7 | 53 | 65 |
NP27 | 3:1 | PLGA7 | Pluronic F127 | 2 | EA | 1:10 | 70 | 15 | 377 ± 4 | 0.393 ± 0.051 | −23.9 ± 1.9 | 31 | 35 |
NP28 | 2:1 | PLGA24 | Tween 80 | 1 | EA | 1:5 | 35 | 10 | 225 ± 2 | 0.269 ± 0.042 | −17.8 ± 1.7 | 41 | 49 |
NP29 | 2:1 | PLGA7 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 182 ± 3 | 0.157 ± 0.023 | −15.7 ± 2.3 | 38 | 30 |
NP30 | 1:1 | PLGA7 | PVA | 2 | DCM | 1:10 | 15 | 15 | 165 ± 4 | 0.263 ± 0.015 | −12.5 ± 0.4 | 4 | 6 |
NP31 | 1:1 | PLGA7 | Pluronic F127 | 2 | EA | 1:10 | 70 | 5 | 345 ± 3 | 0.393 ± 0.045 | −12.1 ± 1.1 | 13 | 28 |
NP32 | 3:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 202 ± 2 | 0.179 ± 0.035 | −22.6 ± 3.9 | 44 | 37 |
NP33 | 1:1 | PLGA7 | Pluronic F127 | 0.5 | DCM | 1:10 | 15 | 15 | 232 ± 2 | 0.198 ± 0.024 | −23.5 ± 1.2 | 14 | 26 |
NP34 | 3:1 | PLGA30 | PVA | 0.5 | EA | 1:1 | 70 | 15 | 173 ± 3 | 0.118 ± 0.021 | −9.2 ± 1.1 | 36 | 57 |
NP35 | 1:1 | PLGA30 | Pluronic F127 | 2 | EA | 1:1 | 15 | 5 | 93 ± 2 | 0.275 ± 0.053 | −7.9 ± 1.4 | 24 | 17 |
NP36 | 1:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 152 ± 3 | 0.235 ± 0.014 | −16.7 ± 1.2 | 27 | 9 |
NP37 | 3:1 | PLGA7 | PVA | 0.5 | EA | 1:10 | 15 | 15 | 239 ± 2 | 0.164 ± 0.032 | −9.1 ± 0.3 | 11 | 65 |
NP38 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:10 | 35 | 10 | 178 ± 2 | 0.226 ± 0.035 | −13.3 ± 2.5 | 15 | 29 |
NP39 | 1:1 | PLGA30 | PVA | 2 | DCM | 1:10 | 70 | 5 | 221 ± 2 | 0.164 ± 0.003 | −13.5 ± 1.9 | 8 | 29 |
NP40 | 1:1 | PLGA30 | PVA | 2 | EA | 1:1 | 70 | 15 | 118 ± 3 | 0.187 ± 0.013 | −8.1 ± 0.9 | 35 | 25 |
NP41 | 3:1 | PLGA7 | Pluronic F127 | 2 | DCM | 1:10 | 15 | 15 | 418 ± 5 | 0.468 ± 0.022 | −11.4 ± 4.1 | 32 | 38 |
NP42 | 3:1 | PLGA30 | Pluronic F127 | 0.5 | DCM | 1:1 | 15 | 5 | 337 ± 4 | 0.144 ± 0.006 | −21.3 ± 1.1 | 37 | 55 |
NP43 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 242 ± 2 | 0.238 ± 0.011 | −20.1 ± 0.9 | 43 | 44 |
NP44 | 3:1 | PLGA30 | Pluronic F127 | 2 | EA | 1:10 | 70 | 5 | 315 ± 3 | 0.473 ± 0.018 | −16.4 ± 0.4 | 35 | 36 |
NP45 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 5 | 175 ± 2 | 0.184 ± 0.023 | −20.2 ± 0.6 | 52 | 23 |
NP46 | 3:1 | PLGA30 | PVA | 0.5 | DCM | 1:10 | 70 | 15 | 216 ± 3 | 0.155 ± 0.046 | −9.7 ± 1.1 | 36 | 52 |
NP47 | 3:1 | PLGA30 | Pluronic F127 | 2 | DCM | 1:1 | 70 | 15 | 327 ± 2 | 0.271 ± 0.007 | −3.4 ± 1.4 | 66 | 35 |
NP48 | 1:1 | PLGA7 | PVA | 0.5 | DCM | 1:10 | 70 | 5 | 162 ± 2 | 0.288 ± 0.016 | −16.7 ± 5.6 | 30 | 8 |
NP49 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 15 | 10 | 225 ± 3 | 0.205 ± 0.018 | −15.7 ± 1.6 | 32 | 27 |
NP50 | 2:1 | PLGA24 | Tween 80 | 1 | DCM | 1:5 | 35 | 10 | 354 ± 4 | 0.416 ± 0.023 | −19.9 ± 1.5 | 34 | 43 |
NP51 | 2:1 | PLGA30 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 220 ± 2 | 0.175 ± 0.018 | −24.5 ± 1.1 | 39 | 37 |
NP52 | 1:1 | PLGA30 | PVA | 0.5 | DCM | 1:10 | 15 | 5 | 209 ± 3 | 0.212 ± 0.024 | −16.9 ± 0.6 | 25 | 49 |
NP53 | 2:1 | PLGA24 | Tween 80 | 0.5 | DMSO | 1:5 | 35 | 10 | 323 ± 4 | 0.248 ± 0.017 | −16.1 ± 4.7 | 45 | 45 |
NP54 | 3:1 | PLGA7 | PVA | 2 | DCM | 1:1 | 70 | 15 | 302 ± 5 | 0.166 ± 0.050 | −15.0 ± 2.1 | 34 | 59 |
NP55 | 1:1 | PLGA30 | PVA | 0.5 | EA | 1:10 | 70 | 15 | 163 ± 3 | 0.234 ± 0.080 | −17.1 ± 1.1 | 16 | 22 |
NP56 | 1:1 | PLGA7 | Pluronic F127 | 2 | DCM | 1:1 | 15 | 5 | 257 ± 2 | 0.176 ± 0.020 | −17.8 ± 2.1 | 50 | 21 |
NP57 | 2:1 | PLGA24 | Pluronic F127 | 1 | DMSO | 1:5 | 35 | 10 | 197 ± 4 | 0.212 ± 0.030 | −15.6 ± 4.6 | 49 | 55 |
NP58 | 3:1 | PLGA30 | Pluronic F127 | 0.5 | EA | 1:10 | 15 | 15 | 373 ± 3 | 0.479 ± 0.050 | −24.5 ± 2.3 | 6 | 20 |
NP59 | 2:1 | PLGA24 | Tween 80 | 1 | DMSO | 1:5 | 35 | 10 | 225 ± 3 | 0.207 ± 0.030 | −22.4 ± 2.9 | 44 | 30 |
NP60 | 1:1 | PLGA30 | PVA | 0.5 | DCM | 1:1 | 15 | 15 | 311 ± 3 | 0.150 ± 0.050 | −18.2 ± 1.6 | 63 | 67 |
Response | Source | Sum of Squares | Degree of Freedom | Mean Square | F-Value | p-Value | |
---|---|---|---|---|---|---|---|
Size | Model | 4.293 × 105 | 44 | 9757.75 | 3.33 | 0.0071 | significant |
Pure error | 4664.39 | 5 | 932.88 | ||||
Residual | 43,955.54 | 15 | 2930.37 | ||||
Lack of fit | 39,291.15 | 10 | 3929.11 | 4.21 | 0.0630 | ||
Cor total | 4.733 × 105 | 59 | |||||
Loading efficiency | Model | 15,793.89 | 36 | 438.72 | 8.98 | <0.0001 | significant |
PureError | 100.33 | 5 | 20.07 | ||||
Residual | 1124.08 | 23 | 48.87 | ||||
LackofFit | 1023.75 | 18 | 56.88 | 2.83 | 0.1263 | ||
CorTotal | 16,917.98 | 59 |
Name | Goal | Lower Limit | Upper Limit |
---|---|---|---|
PLGA:RIF ratio | Is in range | 1:1 | 1:3 |
MW of PLGA | Is in range | 7000–17,000 | 30,000–60,000 |
Surfactant | Is in range | PVA | Tween80 |
Organic solvent | Is equal to DCM | DCM | EA |
Homogenization power | Is equal to 70 W | 15 W | 70 W |
Homogenization time | Is in range | 5 min | 15 min |
Organic and aqueous phase ratio | Is equal to 1:1 | 1:1 | 1:10 |
Size | Minimize | 93.4 | 451.8 |
Loading efficiency | Maximize | 4 | 88.2 |
Size, nm | PDI | Zeta Potential, mV | Encapsulation Efficiency, % | Loading Efficiency, % | Yield, % | |
---|---|---|---|---|---|---|
Predicted | 228 | 0.120 | −24 | 93 | 70 | 45 |
Experimental | 223 ± 2 | 0.110 ± 0.01 | −26 ± 2 | 91 ± 2 | 67 ± 1 | 47 ± 2 |
Error (%) | 2.2 | 9.1 | 7.7 | 2.2 | 4.5 | 4.3 |
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Yessentayeva, N.A.; Galiyeva, A.R.; Daribay, A.T.; Sadyrbekov, D.T.; Moustafine, R.I.; Tazhbayev, Y.M. Optimization of Polylactide-Co-Glycolide-Rifampicin Nanoparticle Synthesis, In Vitro Study of Mucoadhesion and Drug Release. Polymers 2024, 16, 2466. https://doi.org/10.3390/polym16172466
Yessentayeva NA, Galiyeva AR, Daribay AT, Sadyrbekov DT, Moustafine RI, Tazhbayev YM. Optimization of Polylactide-Co-Glycolide-Rifampicin Nanoparticle Synthesis, In Vitro Study of Mucoadhesion and Drug Release. Polymers. 2024; 16(17):2466. https://doi.org/10.3390/polym16172466
Chicago/Turabian StyleYessentayeva, Nazgul A., Aldana R. Galiyeva, Arailym T. Daribay, Daniyar T. Sadyrbekov, Rouslan I. Moustafine, and Yerkeblan M. Tazhbayev. 2024. "Optimization of Polylactide-Co-Glycolide-Rifampicin Nanoparticle Synthesis, In Vitro Study of Mucoadhesion and Drug Release" Polymers 16, no. 17: 2466. https://doi.org/10.3390/polym16172466