Nanostructured Lipid Carriers Engineered as Topical Delivery of Etodolac: Optimization and Cytotoxicity Studies

Etodolac (ETD), a nonsteroidal anti-inflammatory drug, exhibits antinflammatory, analgesic, and antipyretic activity. The main type of ETD administration is oral route, which is associated with significant systemic side effects. Nanostructured lipid carriers (NLC), a modern lipid formulation, are non-toxic, biocompatible, can improve the solubility and stability of drugs. Nanostructured lipid carriers (NLC) containing etodolac were prepared by a melt-emulsification and ultrasonication technique. Full factorial design (FFD) was applied to optimize the composition of NLC and their properties such as zeta potential, polidyspersity index, and entrapment efficiency. Formulations consisting of Capryol 90, glicerol monostearate, and Tween 20 displayed particle size below 300 nm, encapsulated drug with efficiency of approximately 87% and prolonged drug release up to 24 h. Stable formulations displayed moderately negative surface charge suggesting their limited ability to interact with skin surface but simultaneously presenting their lower risk to cause cell-membrane disruption. In fact, cytotoxicity assessment using human dermal fibroblasts and human epidermal keratinocytes revealed that etodolac-loaded NLC had no important impact on skin cells viability evaluated in vitro, which might evidence that NLC formulations are safe for dermal delivery. The studies developed were relatively fast and simple, requiring no specialized equipment method to prepare NLC as ETD carriers ensuring better solubility and prolonged drug release.

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Persea americanaMill. Seed: Fractionation, Characterization, and Effects on Human Keratinocytes and Fibroblasts

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/391247 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Maria del R. Ramos-Jerz ◽

Socorro Villanueva ◽

Gerold Jerz ◽

Peter Winterhalter ◽

Alexandra M. Deters

Keyword(s):

Chlorogenic Acid ◽

Dermal Fibroblasts ◽

Persea Americana ◽

Epidermal Keratinocytes ◽

Hacat Keratinocytes ◽

Human Epidermal Keratinocytes ◽

Residual Solvent ◽

Keratinocyte Proliferation ◽

Normal Human

Methanolic avocado (Persea americanaMill., Lauraceae) seed extracts were separated by preparative HSCCC. Partition and HSCCC fractions were principally characterized by LC-ESI-MS/MS analysis. Theirin vitroinfluence was investigated on proliferation, differentiation, cell viability, and gene expression on HaCaT and normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF). The methanol-water partition (M) from avocado seeds and HSCCC fraction 3 (M.3) were mostly composed of chlorogenic acid and its isomers. Both reduced NHDF but enhanced HaCaT keratinocytes proliferation. HSCCC fractionM.2composed of quinic acid among chlorogenic acid and its isomers inhibited proliferation and directly induced differentiation of keratinocytes as observed on gene and protein level. Furthermore,M.2increased NHDF proliferation via upregulation of growth factor receptors. Salidrosides and ABA derivatives present in HSCCC fractionM.6increased NHDF and keratinocyte proliferation that resulted in differentiation. The residual solvent fractionM.7contained among low concentrations of ABA derivatives high amounts of proanthocyanidins B1 and B2 as well as an A-type trimer and stimulated proliferation of normal cells and inhibited the proliferation of immortalized HaCaT keratinocytes.

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Fabrication of Vesicular Drug Delivery of Niosomal Topical Formulation for the Effective Treatment of Osteoarthritis

Nano Hybrids and Composites ◽

10.4028/www.scientific.net/nhc.12.1 ◽

2016 ◽

Vol 12 ◽

pp. 1-8

Author(s):

S. Nagalakshmi ◽

T. Sandeep ◽

S. Shanmuganathan

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Methyl Cellulose ◽

Entrapment Efficiency ◽

Lipid Vesicles ◽

Tween 20 ◽

Injection Method ◽

Topical Gel ◽

Release Studies

Delivery of drug through topical route, delivers most convenient and novel approach. The Skin can offer several advantages as a route of drug administration although its barrier nature makes it difficult for most drugs to penetrate in to and permeate through it. During the past decades there has been a lot of interest in lipid vesicles as a tool to improve topical drug delivery. Vesicular system such as liposomes, niosomes, ethosomes and elastic deformable vesicles provide an alternative for improved skin drug delivery. In fact vesicles can act as drug carriers controlling drug release. The Research findings were intended to develop sustained release of aceclofenac niosomes formulations in order to reduce gastrointestinal disturbances and to provide better effect when applied topically. Niosomes of aceclofenac was prepared by modified ether injection method using different ratio of surfactants (Tween 20, 40, 60 & 80) with cholesterol and drug. The developed formulations were optimized based on the high entrapment efficiency and in-vitro release studies. Optimized batch was selected and made in to topical niosomal gel using gelling agents like carbopol and sodium carboxy methyl cellulose. Formulation were evaluated for various parameters like vesicle shape, vesicle size, entrapment efficiency, drug content, compatibility studies, in-vitro release studies and stability studies. Ether injection method was found to be most satisfactory in terms of niosome particle size, drug entrapment efficiency was found to be 88.68 ±0.64 % and in-vitro release studies showed 40% of sustain drug release at the end of 8 hrs of study when compared with marketed formulation. Hence, the formulated niosomal topical gel was found to be a better alternative when compared to the marketed formulation in terms of better efficacy, bioavailability and permeation.

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Formulation and Evaluation of Clarithromycin Loaded Nanostructured Lipid Carriers for the Treatment of Acne

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i40b32260 ◽

2021 ◽

pp. 26-38

Author(s):

Pooja Shettigar ◽

Marina Koland ◽

S. M. Sindhoor ◽

Ananth Prabhu

Keyword(s):

Electron Microscopy ◽

Particle Size ◽

Drug Release ◽

Ex Vivo ◽

Entrapment Efficiency ◽

Nanostructured Lipid Carriers ◽

In Vitro Drug Release ◽

Ex Vivo Permeation ◽

Acne Treatment

Background: Clarithromycin is a macrolide antibiotic used in acne treatment, but it has poor solubility, which decreases its permeability through lipid barriers such as skin. Nanostructured lipid carriers can enhance the permeability of clarithromycin through the skin, thus improving its potential for controlling acne. Aim: To formulate and evaluate Nanostructured lipid carriers of clarithromycin for topical delivery in acne treatment Methods: Nanostructured lipid carriers were prepared by emulsification and ultrasonication methods using lipids such as glycerol monostearate and oleic with poloxamer 188 as stabilizer. These nano-carriers were optimized with the help of the Quality by Design (QbD) approach employing Design-Expert® software. The nanoparticles were characterized for particle size analysis, zeta potential, drug-excipient compatibility, entrapment efficiency, and surface morphology by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The nano-carriers were also investigated for in vitro drug release and ex vivo permeation through excised goat skin. The optimized formulation was incorporated into topical carbopol gel base, formulated and examined for pH, viscosity, spreadability, in vitro drug release, ex vivo permeation, and stability under accelerated conditions. Results: The average particle size of the optimized nanoparticles was 164.8 nm, and zeta potential was -39.2 mV. FTIR studies showed that drug and lipids are compatible with each other. The morphology study by SEM and TEM showed spherical shaped particles. The entrapment efficiency of the optimized formulation was found to be 88.16%. In vitro drug release studies indicated sustained release from the formulation due to diffusion through the lipid matrix of the particles. The ex vivo permeation study using goat skin produced greater permeation from the NLC gel (89.5%) than marketed gel (65%) due to the lipid solubility of the nanoparticles in the skin. The formulation was stable under accelerated conditions. Conclusion: The optimized formulation can be considered as promising nano-carriers suitable for the sustained release of clarithromycin into the skin for effective control of acne.

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Innate immune response of human epidermal keratinocytes and dermal fibroblasts to in vitro incubation of Trichophyton benhamiae DSM 6916

Journal of the European Academy of Dermatology and Venereology ◽

10.1111/jdv.15472 ◽

2019 ◽

Vol 33 (6) ◽

pp. 1177-1188 ◽

Cited By ~ 3

Author(s):

J. Hesse‐Macabata ◽

B. Morgner ◽

S. Morgenstern ◽

M.O. Grimm ◽

P. Elsner ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Dermal Fibroblasts ◽

Innate Immune ◽

Epidermal Keratinocytes ◽

Human Epidermal Keratinocytes ◽

In Vitro Incubation ◽

Trichophyton Benhamiae

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In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties

Molecules ◽

10.3390/molecules27020491 ◽

2022 ◽

Vol 27 (2) ◽

pp. 491

Author(s):

Eduardo Perez ◽

Jose R. Fernandez ◽

Corey Fitzgerald ◽

Karl Rouzard ◽

Masanori Tamura ◽

...

Keyword(s):

Human Skin ◽

Cannabis Sativa ◽

Transepidermal Water Loss ◽

Dermal Fibroblasts ◽

Ultraviolet B ◽

Epidermal Keratinocytes ◽

Yeast Fermentation ◽

Lauryl Sulfate ◽

Human Epidermal Keratinocytes

Cannabigerol (CBG) is a minor non-psychoactive cannabinoid present in Cannabis sativa L. (C. sativa) at low levels (<1% per dry weight) that serves as the direct precursor to both cannabidiol (CBD) and tetrahydrocannabinol (THC). Consequently, efforts to extract and purify CBG from C. sativa is both challenging and expensive. However, utilizing a novel yeast fermentation technology platform, minor cannabinoids such as CBG can be produced in a more sustainable, cost-effective, and timely process as compared to plant-based production. While CBD has been studied extensively, demonstrating several beneficial skin properties, there are a paucity of studies characterizing the activity of CBG in human skin. Therefore, our aim was to characterize and compare the in vitro activity profile of non-psychoactive CBG and CBD in skin and be the first group to test CBG clinically on human skin. Gene microarray analysis conducted using 3D human skin equivalents demonstrates that CBG regulates more genes than CBD, including several key skin targets. Human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (NHEKs) were exposed in culture to pro-inflammatory inducers to trigger cytokine production and oxidative stress. Results demonstrate that CBG and CBD reduce reactive oxygen species levels in HDFs better than vitamin C. Moreover, CBG inhibits pro-inflammatory cytokine (Interleukin-1β, -6, -8, tumor necrosis factor α) release from several inflammatory inducers, such as ultraviolet A (UVA), ultraviolet B (UVB), chemical, C. acnes, and in several instances does so more potently than CBD. A 20-subject vehicle-controlled clinical study was performed with 0.1% CBG serum and placebo applied topically for 2 weeks after sodium lauryl sulfate (SLS)-induced irritation. CBG serum showed statistically significant improvement above placebo for transepidermal water loss (TEWL) and reduction in the appearance of redness. Altogether, CBG’s broad range of in vitro and clinical skin health-promoting activities demonstrates its strong potential as a safe, effective ingredient for topical use and suggests there are areas where it may be more effective than CBD.

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N-Succinyl-S-Farnesyl-L-Cysteine (SFC): A Novel Isoprenylcysteine Analog with In Vitro Anti-Inflammatory Activity and Clinical Skin Protecting Properties

Cosmetics ◽

10.3390/cosmetics8040110 ◽

2021 ◽

Vol 8 (4) ◽

pp. 110

Author(s):

José R. Fernández ◽

Karl Rouzard ◽

Corey Fitzgerald ◽

Jason Healy ◽

Masanori Tamura ◽

...

Keyword(s):

Small Molecule ◽

Dermal Fibroblasts ◽

Epidermal Keratinocytes ◽

Double Blind ◽

Human Epidermal Keratinocytes ◽

New Class ◽

Normal Human ◽

Anti Inflammatory ◽

Split Face

Over the past 15 years, small molecule isoprenylcysteine (IPC) analogs have been identified as a potential new class of topical anti-inflammatories. Clinical studies have demonstrated that IPCs are both safe and effective in promoting healthy skin when applied topically. This work aims to demonstrate N-Succinyl-S-farnesyl-L-cysteine (SFC) as a novel IPC molecule that provides a broad spectrum of benefits for skin. Human promyelocytic cell line HL-60, human dermal microvascular endothelial cells (HDMECs), human dermal fibroblasts (HDFs), and normal human epidermal keratinocytes (NHEKs) were exposed in culture to various inducers to trigger reactive oxygen species, cytokines, or collagenase production. A 49-subject randomized double-blind, vehicle-controlled, split face trial was performed with 1% SFC gel, or 5% niacinamide and vehicle applied for 12 weeks to evaluate anti-wrinkle and anti-aging endpoints. We demonstrated that SFC inhibited GPCR and TLR-induced pro-inflammatory cytokine release in NHEKs and HDMECs from several inflammatory inducers such as UVB, chemicals, cathelicidin, and bacteria. SFC successfully reduced GPCR-induced oxidation in differentiated neutrophils. Moreover, photoaging studies showed that SFC reduced UVA-induced collagenase (pro-MMP-1) production in HDFs. Clinical assessment of 1% SFC gel demonstrated improvement above the vehicle for wrinkle reduction, hydration, texture, and overall appearance of skin. N-Succinyl-S-farnesyl-L-cysteine (SFC) is a novel anti-inflammatory small molecule and is the first farnesyl-cysteine IPC shown to clinically improve appearance and signs of aging, while also having the potential to ameliorate inflammatory skin disorders.

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A Novel Substance P-Based Hydrogel for Increased Wound Healing Efficiency

Molecules ◽

10.3390/molecules23092215 ◽

2018 ◽

Vol 23 (9) ◽

pp. 2215 ◽

Cited By ~ 4

Author(s):

Da Kim ◽

Ji Jang ◽

Song Jang ◽

Jungsun Lee

Keyword(s):

Wound Healing ◽

Substance P ◽

Dermal Fibroblasts ◽

Epidermal Keratinocytes ◽

Human Epidermal Keratinocytes ◽

In Vivo Experiments ◽

And Migration ◽

Proliferation And Migration

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.

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Pharmaceutical evaluation of atorvastatin-loaded nanostructured lipid carriers incorporated into the gelatin/hyaluronic acid/polycaprolactone scaffold for the skin tissue engineering

Journal of Biomaterials Applications ◽

10.1177/0885328220970760 ◽

2020 ◽

pp. 088532822097076

Author(s):

Mahsa Ahmadi ◽

Mehdi Mehdikhani ◽

Jaleh Varshosaz ◽

Shadi Farsaei ◽

Hadis Torabi

Keyword(s):

Particle Size ◽

Hyaluronic Acid ◽

Drug Release ◽

Zeta Potential ◽

Mtt Assay ◽

Dermal Fibroblasts ◽

Skin Regeneration ◽

Nanostructured Lipid Carriers ◽

In Vitro Degradation

In this study, gelatin/hyaluronic acid (HA) scaffolds containing different amounts of atorvastatin-loaded nanostructured lipid carriers (NLCs) coated entirely with polycaprolactone (PCL) film were fabricated for skin regeneration. 12 atorvastatin-loaded NLCs formulations were synthesized, and particle size, zeta potential, drug entrapment efficiency (EE), and drug release of the formulations were determined. The optimum freeze-dried atorvastatin-loaded NLCs were added in 3 different weight percentages to the gelatin and HA membranous scaffolds. Thereafter, the membranes were coated entirely by a thin layer of the PCL. They were characterized, and then mechanical properties, in vitro degradation and in vitro drug release were assessed. Moreover, human dermal fibroblasts (HDF) were cultured on the prepared nanocomposite scaffolds in order to investigate the cytotoxicity by the MTT assay after the first day, third day, and fifth day. Results revealed that the most favorable atorvastatin-loaded NLCs had 99.54 nm average particle size, −24.30 mV zeta potential, 97.98% EE, and 75.24% drug release within 237 hrs. Mechanical tests indicated that all the three scaffolds had approximately a 90 MPa elastic modulus which was more than two-fold of tensile modulus of normal human skin. The in vitro degradation test demonstrated that the membranes were degraded up to 98% after 5 days, and the scaffolds drug release efficiency (DRE) was in a range of 75–79% during those 5 days. The MTT assay results confirmed the cytocompatibility of the scaffolds. The scaffold containing 54.1 wt% NCLs was the optimum sample (S3). Scanning Electron Microscopy (SEM) images of the latter one showed the uniform distribution of the NLCs with an average size of 150 nm, and the images of cultured HDF illustrated the good cell attachment. In conclusion, suitable physicochemical and biological properties of the novel gelatin/HA/PCL nanocomposite scaffold containing 54.1 wt% atorvastatin-loaded NLCs (S3) can be a good candidate for skin regeneration.

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Biocompatibility and Antimicrobial Activity of Nanostructured Lipid Carriers for Topical Applications Are Affected by Type of Oils Used in Their Composition

Pharmaceutics ◽

10.3390/pharmaceutics13111950 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1950

Author(s):

Dragana P. C. de Barros ◽

Patricia Reed ◽

Marta Alves ◽

Rafaela Santos ◽

Abel Oliva

Keyword(s):

Antimicrobial Activity ◽

Therapeutic Potential ◽

Antimicrobial Properties ◽

Dermal Fibroblasts ◽

Nanostructured Lipid Carriers ◽

Epidermal Keratinocytes ◽

Drug Bioavailability ◽

Human Epidermal Keratinocytes ◽

Strong Argument ◽

Natural Oils

Nanostructured lipid carriers (NLCs) have gained significant attention as tools for the dermal delivery of therapeutics due to their stability, biocompatibility, and ability to improve drug bioavailability. The use of natural plant oils (NPO) in NLC formulations has numerous benefits for the skin due to their therapeutic potential. This work shows the effect of NLC composition on bioavailability in epidermal cells and antimicrobial activity against Staphylococcus aureus. Sixteen systems containing fixed (sunflower, olive, corn, peanut, coconut, castor, and sweet almond) and essential (eucalyptus) oils, with different solid lipid (SL): liquid lipid (LL) ratios, were engineered. The structural properties, bioavailability, and antimicrobial action of the particles was studied. The choice of NPO influenced the physicochemical stability by changing the diameter of NLC formulations (between 160 nm and 185 nm) and Z-potential (between −46 mV and −61 mV). All of the systems were characterized by concentration-dependent cytocompatibility with human epidermal keratinocytes (HaCaT) and human dermal fibroblasts (HDFn). The SL:LL ratio in some NLC systems impacted cell cytotoxicity differently. Antimicrobial properties were observed in all 16 systems; however, the type of oil and SL:LL ratio affected the activity of the formulations. Two NLC-NPO systems were found to be non-cytotoxic to human cells lines at concentrations that completely inhibited bacterial growth. These results present a strong argument that the use of natural oils in NLC formulations presents a promising tool for the treatment of skin infections.

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