The Application of Nanogels as Efficient Drug Delivery Platforms for Dermal/Transdermal Delivery
Abstract
:1. Introduction
2. Skin, the Largest Human Body Organ
2.1. Healthy and Diseased Skin Anatomy and Its Role as Barrier for Delivery
2.2. Dermal and Transdermal Delivery of Drugs
3. Applications of Nanogels as Drug Delivery Carriers
Active Pharmaceutical Ingredient | Preparation Method | Nano Structure Explanation | Application Route | Application | Evaluation Methods | Ref. |
---|---|---|---|---|---|---|
Flurbiprofen | Flurbiprofen was dissolved in the water phase. It was then heated to 60 °C, and the cross-linker was mixed. This aqueous part was then dispersed with the organic phase. Finally, water and dichloromethane were evaporated. | Flurbiprofen-loaded nanogel | Dermal | Drug-free nanogel in HPMC gel, drug-free HPMC gel, and drug-loaded nanogel in HPMC gel formulations was applied for in vivo skin irritation test. | Polydispersity index (PDI), drug content, particle size, zeta potential, pH, visual examination, rheological studies, viscosity, in vivo skin irritation test, permeation, in vitro release, stability | [50] |
Meloxicam | Solid lipid nanoparticles (MLX-SLN)-based nanogels containing drugs were studied by microemulsion template technique. Carbopol 940 was dissolved and neutralized by adding triethanolamine. | SLN-based nanogel (SLN-gel) | Dermal | Drug-SLN-contained Carbopol gel and drug-free SLN Carbopol gel were applied for skin tolerance tests and evaluation of pharmacodynamic activity. | Entrapment efficiency (EE), in vitro skin occlusivity, rheological behavior, skin deposition, effect on stratum corneum, in vitro skin permeation, pharmacodynamic activity, skin tolerance | [134] |
Aloe-emodin, Acitretin | Chitin nanogels were prepared by regeneration chemistry. The drug solution was added. Remaining steps are centrifugation and sonication. | Aloe-emodin, Acitretin-loaded Nanogel | Dermal | Chitin nanogels, acitretin-loaded chitin nanogels and aloe-emodin-loaded chitin nanogels for evaluation of anti-psoriatic activity and skin irritation study. | Swelling, ex vivo skin permeation, drug retention, in vitro drug release, rheology, in vitro haemolysis assay, cytotoxicity, stability, skin irritation, in vivo anti-psoriatic activity | [135] |
Ganoderma lucidum (GLT) | A high-pressure homogenization technique was used to prepare GLT nanosuspensions. Lyofilised GLT nanosuspension was put on the Carbopol 940P mixture. | Freeze-dried GLT nanosuspension powders contained in nanogels | Dermal | GLT nanogel was applied for skin irritation and GLT–Carbopol gel and GLT nanogel were applied for their pharmacodynamic efficacy. | Zeta potential, particle size, drug content, spreadability, pH, in vitro skin permeation pharmacodynamic efficacy | [136] |
GLT | A high-pressure homogenization technique was used to prepare GLT nanosuspensions. Carbopol 940 was mixed in water. Nanosuspension and propylene glycol (PEG) were mixed into the Carbopol 940. | GLT nanosuspensions contained gels | Dermal | GLT nanogel was applied for in vitro permeation and placebo gel, GLT nanogel with no therapeutic ultrasound (TUS) and with TUS were used for pharmacodynamic efficacy. | Zeta potential, particle size, drug content, spreadability, pH, in vitro permeation, in vitro release | [137] |
Brucine (BRC) | Sodium cholate, lipoid S100, cholesterol and brucine were dispersed with ethanol: chloroform mixture and solvent were removed. The dried, thin film was rehydrated with solution. Mixtures were put in a sonicator to reduce size. | BRC-loaded transliposomes (BRC-TL) contained nanogel | Dermal | BRC-TL, placebo TL and BRC suspension were applied for in vitro cytotoxicity study. | Vesicle size, PDI, drug release, antioxidant properties, EE, pH, firmness, consistency, cohesiveness, viscosity, skin permeation, dermatokinetic study, in vitro cytotoxicity | [138] |
Tacrolimus | Ring-opening copolymerization of glycidol and succinic anhydride as a new synthetic production method was studied enzymatically. Novozyme 435 was used for the esterification of oligomers. | Tacrolimus-loaded nanogel | Dermal | Nanogels were loaded with tacrolimus and applied for skin penetration, cell viability | Skin penetration, cell viability | [139] |
Dexamethasone | With a new technique, a supramolecular polymer nanogel was designed that uses host–guest interactions between groups of arene and alkyl chains on the hyperbranched polyglycerol backbone. | Supramolecular polymer nanogels | Dermal | Dye-labeled supramolecular assemblies and supramolecular polymer nanogels were employed to conduct a skin penetration study | Degradation, cell viability, skin penetration, drug release | [28] |
Hyaluronic acid/β-glucan | HAMA-OVA and SPGMA were dissolved in phosphate-buffered saline (PBS) and put as a photoinitiator into mixtures. These solutions were mixed, and they were cured. Gels were mixed in PBS, then filtered through a syringe filter. | Hyaluronic acid/β-glucan hybrid nanogels | Dermal | The rhodamine B-labeled nanogels were applied for skin penetration. | Particle analysis, cell culture, skin penetration, flow cytometry, polymerase chain reaction | [17] |
Lemongrass (Cymbopogon citratus) oil | Encapsulation of lemongrass oil was conducted with the ionic gelation technique. Acrylate was added to convert the emulsion into a gel. | Chitosan-encapsulated lemongrass nanogel | Dermal | The chitosan nanoparticles entrapped in acrylate gel were applied for dermal toxicity. | Fourier Transform Infrared (FTIR), TEM, wash durability, encapsulation efficiency, stability, X-ray diffraction pattern (XRD), durability of nanogel against crocking and perspiration, subacute toxicity, Dynamic Light Scattering (DLS) | [140] |
Lidocaine | To prepare the nanoemulsion, lidocaine was dissolved in oleic acid, then an emulsifier was added. Water was put into the mixture slowly. Prepared coarse nanoemulsion was sonicated. It was added to the dispersion of Carbopol 940 with a gelling agent. | Lidocaine-loaded nanoemulsion-based nanogel | Dermal | Topical nanogel and conventional gel were applied for in vivo skin safety study. | Particle size, PDI, percent transmittance, thermodynamic stability, refractive index, zeta potential, pH, morphological evaluation, in vivo skin safety, drug content, extrudability, spreadability, drug release, dermatokinetic study, stability | [141] |
Methotrexate | Methanol was added to a chitin-saturated dispersion in methanol calcium chloride mixture by mixing, and it was sonicated. Methotrexate was mixed, centrifugated and sonicated. | Methotrexate-loaded chitin nanogel (MCNG) | Dermal | MCNG with a conventional Carbopol gel was applied for in vivo anti-psoriatic studies and toxicity studies. | EE, loading efficiency, in vivo anti-psoriatic activity, drug release, swelling, skin permeation, cell culture studies, subacute toxicity | [142] |
Nisin | Nisin and chitosan were dissolved in citrate buffer. Nisin solution was added to the chitosan slowly. The solution was mixed. For electrostatic interactions, 250-watt power was applied to the solution. This solution was to separate unloaded drugs. | Chondroitin sulfate-Nisin nanogels (CS-N NGs) | Dermal | - | Loading efficiency, DLS, swelling, field-emission scanning electron microscopy (FESEM), loading capacity, in vitro degradation, antibacterial activity, cell viability, in vitro drug release | [143] |
Temozolomide | Polylactic-glycolic acid (PLGA) and temozolomide were dispersed in dichloromethane and stirred with polyvinyl alcohol (PVA) solution. The coarse emulsion was with a homogenizer. It was evaporated, cross-linked by sodium triployphosphate (TPP), stirred and lyophilized. Temozolomide-encapsulated lyophilized nanoparticles were mixed in the Pluronic F-127 gel system. | Lyophilized drug-encapsulated PLGA-chitosan nanoparticles contained nanogel | Transdermal | - | Scanning Electron Microscopy (SEM), particle size, PDI, Thermogravimetry, Differential Thermal Analysis (DTA), Differential Scanning Colorimetry (DSC), rheology, stability, Transmission Electron Microscopy (TEM), sol-gel fraction, EE, porosity, turbidity, sedimentation rate, stability, ex vivo skin permeation, biocompatibility, in vitro drug release | [45] |
Diclofenac sodium | Semisolid gels: PEG, water, diclofenac sodium, Tween 20 and DMSO were mixed, and gellan gum was slowly added to this crease and dissolved. Mineral oil was added and mixed. Calcium chloride, isopropyl alcohol, was added and homogenized.Solid hydrogel film: PEG, water, Tween 20, DMSO and diclofenac sodium were mixed, and gellan gum was added slowly and heated at 75 °C. After the gum was thawed, the temperature was slowly lowered. Isopropyl alcohol was added. Calcium chloride was added as a cross-linker. The hydrogels were poured into solid gels and cured. | Diclofenac sodium-loaded temperature and pH-responsive core–shell nanogel | Transdermal | - | DLS, in vitro release, Attenuated Total Reflectance Fourier Transforms Infrared Spectroscopy (ATR-FTIR), SEM | [144] |
Caffeine | Poly(NIPAM-co-AAc) nanogel was performed with an easy emulsion polymerization. A post-production method was used to load the caffeine into the produced nanogel particles. Caffeine was included in lyophilized nanogel with magnetic stirrers. The mixture was ultrasonicized and incubated at 2–4 °C and ~25 °C. | Caffeine-loaded poly(NIPAM-co-AAc) nanogel | Transdermal | Caffeine-loaded poly(NIPAM-co-AAc), caffeine-loaded poly(NIPAM-co-AAc), followed by aqueous solution of pH modulator (CA), caffeine-loaded polyNIPAM, caffeine-loaded poly(NIPAM-co-AAc)-RT, caffeine-loaded poly(NIPAM-co-AAc)-RT, followed by aqueous solution of CA, caffeine-loaded polyNIPAM-RT, saturated aqueous solution of caffeine were used for skin permeation. | Quantitative analysis, particle size, in vitro skin permeation, size distribution, effects of temperature, thermal analysis, pH, TEM, swelling behavior, EE | [145] |
Artemether (ART) | For NLC, artemether was mixed at 90 °C, Gelucire, P85G, Transcutol, ethanol added, and Tween 80 added, homogenized with Polytron, and lyophilized. The polymers were dispersed in water, ethanol and PEG were added. The lyophilized NLC formulation was added and mixed well. pH adjusted. | Nanostructured lipid carrier (NLC) contained gel (nanogel) | Transdermal | ART-NLC (1.5 g dispersed in 1 mL of 1:1 water–ethanol mixture, equivalent to 33 mg of ART) was applied for in vivo transdermal anti-plasmodial activity. One gram of ART-nanogels contained 12.5 mg of ART, whereas 1 g of ART-NLC containing 22 mg of ART was applied for skin tolerance test. | Zeta potential, particle size, PDI, size distribution, TEM, DLS, DSC, encapsulation efficiency, in vivo transdermal activity, ex vivo tape stripping, pH, spreadability, in vitro occlusivity, rheology, drug content, skin tolerance, ex vivo skin permeation, in vitro drug release | [146] |
Ibuprofen | For polymer–drug nanoconjugates, drug was put in sodium hydroxide and water was added. The drug solution was put into a chitosan dispersion with stirring. Gellan gum was mixed with PEG switch stirring. The drug–chitosan nanoconjugate dispersion was added to the gel at 60 °C. | Ibuprofen–chitosan nanoconjugate contained gel (nanogel) | Transdermal | - | Conjugation efficiency, FTIR, SEM, DSC, rheological studies, thermal gravimetry analysis, pH, swelling, ex vivo skin permeation, drug release, skin retention, | [47] |
Nigella sativa oil, atorvastatin | Chitosan was dispersed in acetic acid solution, and PVA was dissolved in distilled water, which was then mixed to form the water phase. Span was mixed with ethanol, and Sativa oil and atorvastatin were dissolved in ethanol. This was put into the aqueous part to obtain a microemulsion. It was homogenized for nano size. The solution was stirred while the organic phase was evaporated. Cross-linking was achieved by dripping TPP solution into the emulsion. CMC was added and mixed. | Atorvastatin-Nigella sativa oil-loaded nanogel | Transdermal | Oil nanogel and atorvastatin-oil nanogels were used for in vitro skin permeation tests. | Particle size, zeta potential, FTIR, drug loading efficiency, drug release, viscosity, storage, antimicrobial assessment, in vitro cytotoxicity, in vitro wound closure, gene expression analysis, in vitro permeation | [147] |
Gp-100 peptide KVPRNQDWL | The peptide mixture was put into a nanogel dispersion and stirred. pH 6.5 buffer was put into the mixture. The percentage of the peptide to nano gel was optimized for zeta potential. | Antigen peptide-loaded nanogels | Transdermal | Antigen-loaded nanogels were applied for tumor growth inhibition. | Tumor growth inhibition, immunohistochemistry, confocal laser scanning microscopy, | [100] |
Luliconazole | The esterified polymer was dissolved with water on a magnetic stirrer. The drug was added and homogenized, and its macrosuspension was prepared. Nanosuspensions were equipped with Sonicator. Carbopol 934 was dispersed and mixed without adding water to the optimized nanosuspension. pH’ was neutralized. The preservative was added. | Nanosuspension-based nanogel of luliconazole | Transdermal | Formalin (standard), 0.9% w/v NaCl solution (control) and nanogel were applied for skin irritation test. | FTIR, nuclear magnetic resonance analysis, XRD, SEM, DSC, in silico studies, PDI, particle size, zeta potential, EE, spreadability, pH, viscosity, stability, skin irritation, drug content, in vitro skin permeation | [46] |
Methotrexate | The organic part was obtained by stirring the organic phase, magnesium oil and castor oil. The aqueous part was prepared by separately dispersing the aqueous phase, Glycerol, PEG 400, Tween 80 and water. Drug-loaded nanoemulsion was designed by homogenizing the organic and aqueous phases. The preservative was added. Carbopol 940 was added to the mixture and mixed. pH adjusted. | Magnesium oil integrated Methotrexate nanoemulsion-loaded gel (nanoemulgel) | Transdermal | Control groups (DC; CFA treated group), test 1 (MO-S treated group), test 2 (Mtx-MOS) and MTX nanoemulsion contained nanogel were applied for in vivo anti-arthritic activity | PDI, particle size, zeta potential, pH, EE, stability, ex vivo permeation, pharmacokinetics study, in vitro drug release, in vivo anti-arthritic activity | [148] |
3.1. Nanogels for Dermal Delivery of Active Ingredients
3.2. Nanogels for Transdermal Delivery of Active Ingredients
4. Conclusions and Author’s Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Siafaka, P.I.; Özcan Bülbül, E.; Okur, M.E.; Karantas, I.D.; Üstündağ Okur, N. The Application of Nanogels as Efficient Drug Delivery Platforms for Dermal/Transdermal Delivery. Gels 2023, 9, 753. https://doi.org/10.3390/gels9090753
Siafaka PI, Özcan Bülbül E, Okur ME, Karantas ID, Üstündağ Okur N. The Application of Nanogels as Efficient Drug Delivery Platforms for Dermal/Transdermal Delivery. Gels. 2023; 9(9):753. https://doi.org/10.3390/gels9090753
Chicago/Turabian StyleSiafaka, Panoraia I., Ece Özcan Bülbül, Mehmet Evren Okur, Ioannis D. Karantas, and Neslihan Üstündağ Okur. 2023. "The Application of Nanogels as Efficient Drug Delivery Platforms for Dermal/Transdermal Delivery" Gels 9, no. 9: 753. https://doi.org/10.3390/gels9090753