Development and Characterization of n-Propyl Gallate Encapsulated Solid Lipid Nanoparticles-Loaded Hydrogel for Intranasal Delivery
Abstract
:1. Introduction
2. Results
2.1. Quality by Design Approach and Risk Assessment (RA)
2.2. Central Composite Design (CCD)
2.2.1. Optimization and Impact of Critical Parameters on Z-Average, Polydispersity Index (PDI), Zeta Potential
2.2.2. XRPD and FTIR Analysis
2.3. Characterization of Hydrogels
2.3.1. Evaluation of pH and Drug Contents of Hydrogels
2.3.2. Raman Chemical Mapping
2.3.3. Spreadability and Swelling Studies of Hydrogel
2.3.4. Viscosity Measurement
2.3.5. In Vitro Mucoadhesion Study
2.3.6. Morphological Study of PG-SLNs and PG-SLNs-Loaded HG
2.3.7. In Vitro Permeation
2.3.8. In Vitro Release Study
2.3.9. In Vitro Antioxidant Activity Evaluation with Hydrogen Peroxide Scavenging Assay
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Optimization of SLNs by Quality by Design (QbD) Approach and Risk Assessment Strategy
4.3. Response Surface Quadratic Model
4.4. Development of PG-SLNs by Modified Injection Method
4.5. Preparation of Mucoadhesive HA-Based Hydrogel Formulations with PG-SLNs
4.6. Characterization of PG-SLNs
4.6.1. X-ray Powder Diffraction (XRPD)
4.6.2. Fourier-Transformed Infrared Spectroscopy (FTIR)
4.6.3. Measurement of Z-Average, Surface Charge and Polydispersity Index
4.6.4. Encapsulation Efficiency (EE), Loading Capacity (LC) and Percentage Yield Determination
4.6.5. HPLC Method
4.7. Characterization of PG-SLNs Loaded Hydrogels
4.7.1. Physical Appearance, pH and Drug Contents of Hydrogels
4.7.2. Raman Spectroscopy
4.7.3. Swelling Index
4.7.4. Spreadability Test
4.7.5. Viscosity Measurement
4.8. In Vitro Characterization of Nanoparticles and Hydrogel
4.8.1. In Vitro Mucoadhesion Testing
4.8.2. Surface Morphology
4.8.3. In Vitro Permeation Study
4.8.4. In Vitro Release Study
4.8.5. Hydrogen Peroxide Scavenging (H2O2) Assay
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ANOVA | one-way analysis of variance |
BBB | blood–brain barrier |
CNS | central nervous system |
CPPs | critical process parameters |
CMA | critical materials attributes |
CQA | critical quality attributes |
CCD | central composite design |
°C | centigrade |
EE | encapsulation efficiency |
FTIR | Fourier-transformed infrared spectroscopy |
GA | glutaraldehyde |
HA | hyaluronic acid |
HG | hydrogel |
HA-HG | hyaluronic acid—hydrogel |
HPLC | high proficiency liquid chromatography |
H2O2 | hydrogen peroxide |
ICH | International Conference on Harmonization |
KBr | potassium bromide |
kDa | kilo Dalton |
LC | loading capacity |
LOQ | limit of quantification |
LOD | limit of detection |
mV | millivolt |
mm | millimol |
mA | milliampere |
mPa | millipascal |
mg | milligram |
mm2 | square millimeter |
Mw | molecular weight |
nm | nanometer |
ppm | parts per million |
PBS | phosphate buffer saline |
PG | propyl gallate |
PG-SLNs | PG-solid lipid nanoparticles |
PDI | polydispersity index |
Pas | pascal |
QbD | Quality by Design |
QTPP | quality target product profile |
RA | risk assessment |
SLNs | solid lipid nanoparticles |
SEM | scanning electron microscopy |
SLNs-HGnCL | SLNs non-cross-linked HG |
SLNs-HGCL | SLNs cross-linked HG |
TC-P | Transcutol-P |
µm | micrometer |
w/v | weight/volume |
XRPD | X-ray powder diffractograms |
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Number of Runs | Temperature (°C) | Amount of Surfactant (mg) | Amount of Cholesterol (mg) | Z-Average (nm) | PDI | Zeta Potential (mV) |
---|---|---|---|---|---|---|
1 | 45 | 25 | 40 | 150 ± 10 | 0.30 ± 0.01 | −30 ± 8.4 |
2 | 20 | 25 | 40 | 220 ± 5.5 | 0.22 ± 0.02 | −29 ± 6.5 |
3 | 45 | 25 | 40 | 140 ± 4.5 | 0.23 ± 0.02 | −31 ± 8.4 |
4 | 80 | 10 | 40 | 155 ± 5.5 | 0.25 ± 0.05 | −29 ± 8.4 |
5 | 45 | 40 | 40 | 500 ± 6.6 | 0.44 ± 0.07 | −5 ± 7.5 |
6 | 70 | 40 | 20 | 400 ± 7.8 | 0.55 ± 0.01 | −6 ± 8.5 |
7 * | 70 | 10 | 60 | 120 ± 8.8 | 0.12 ± 0.08 | −38 ± 10.2 |
8 | 45 | 25 | 40 | 155 ± 22 | 0.26 ± 0.09 | −29 ± 12 |
9 | 45 | 10 | 40 | 200 ± 2.3 | 0.21 ± 0.08 | −29 ± 5.5 |
10 | 20 | 10 | 20 | 230 ± 2.4 | 0.22 ± 0.06 | −19 ± 6.5 |
11 | 45 | 25 | 40 | 160 ± 40 | 0.25 ± 0.08 | −28 ± 10 |
12 | 45 | 25 | 40 | 145 ± 20 | 0.18 ± 0.05 | −28 ± 10.2 |
13 | 20 | 40 | 60 | 600 ± 12 | 0.46 ± 0.01 | −4 ± 3.3 |
14 | 45 | 25 | 20 | 222 ± 10 | 0.23 ± 0.02 | −20 ± 5.5 |
15 | 45 | 25 | 60 | 190 ± 14 | 0.22 ± 0.02 | −19 ± 6.2 |
HA Content (% w/v) | pH Value | Drug Contents (%) | Spreadability (mm2) | Mucoadhesion Displacement (mm) after 7 h | Viscosity Cross-Linked (Pas) | Viscosity Non-Cross-Linked (Pas) |
---|---|---|---|---|---|---|
0.5 | 5.3 ± 0.2 | 78 ± 2.5 | 222.45 ± 0.22 | 20 * | 0.112 | 0.181 |
1 | 5.2 ± 0.3 | 82 ± 3.3 | 360 ± 0.33 | 20 | 1.88 | 2.11 |
2 | 5.5 ± 0.4 | 80 ± 1.4 | 320 ± 0.44 | 10 | 14.29 | 15.45 |
3 | 5.9 ± 0.6 | 79 ± 4.2 | 340 ± 0.012 | 1 | 66.34 | 157 |
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Sabir, F.; Katona, G.; Ismail, R.; Sipos, B.; Ambrus, R.; Csóka, I. Development and Characterization of n-Propyl Gallate Encapsulated Solid Lipid Nanoparticles-Loaded Hydrogel for Intranasal Delivery. Pharmaceuticals 2021, 14, 696. https://doi.org/10.3390/ph14070696
Sabir F, Katona G, Ismail R, Sipos B, Ambrus R, Csóka I. Development and Characterization of n-Propyl Gallate Encapsulated Solid Lipid Nanoparticles-Loaded Hydrogel for Intranasal Delivery. Pharmaceuticals. 2021; 14(7):696. https://doi.org/10.3390/ph14070696
Chicago/Turabian StyleSabir, Fakhara, Gábor Katona, Ruba Ismail, Bence Sipos, Rita Ambrus, and Ildikó Csóka. 2021. "Development and Characterization of n-Propyl Gallate Encapsulated Solid Lipid Nanoparticles-Loaded Hydrogel for Intranasal Delivery" Pharmaceuticals 14, no. 7: 696. https://doi.org/10.3390/ph14070696