scholarly journals New Strategies for Improving Budesonide Skin Retention

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 30
Author(s):  
Cristina Padula ◽  
Ian Pompermayer Machado ◽  
Aryane Alves Vigato ◽  
Daniele Ribeiro de Araujo
Keyword(s):  
Inclusion Complex ◽  
Water Solubility ◽  
Ex Vivo ◽  
Dermal Absorption ◽  
Poloxamer 407 ◽  
Systemic Absorption ◽  
Receptor Compartment ◽  
Cutaneous Administration ◽  
Skin Retention ◽  
New Strategies

The aim of this work was to evaluate the ex vivo effect of the combination of two strategies, complexation with cyclodextrin, and poloxamer hydrogels, for improving water solubility in the dermal absorption of budesonide. Two hydrogels containing 20% poloxamer 407, alone or in combination with poloxamer 403, were prepared. Each formulation was loaded with 0.05% budesonide, using either pure budesonide or its inclusion complex with hydroxypropyl-β-cyclodextrin, and applied in finite dose conditions on porcine skin. The obtained results showed that for all formulations, budesonide accumulated preferentially in the epidermis compared to the dermis. The quantity of budesonide recovered in the receptor compartment was, in all cases, lower than the LOQ of the analytical method, suggesting the absence of possible systemic absorption. The use of a binary poloxamer mixture reduced skin retention, in line with the lower release from the vehicle. When the hydrogels were formulated with the inclusion complex, an increase in budesonide skin retention was observed with both hydrogels. Poloxamer hydrogel proved to be a suitable vehicle for cutaneous administration of budesonide.

scholarly journals Nanoparticulate Gels for Cutaneous Administration of Caffeic Acid

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 961
Author(s):  
Maddalena Sguizzato ◽  
Paolo Mariani ◽  
Francesca Ferrara ◽  
Markus Drechsler ◽  
Supandeep Singh Hallan ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
Ex Vivo ◽  
Protective Role ◽  
Correlation Spectroscopy ◽  
Poloxamer 407 ◽  
Food Sources ◽  
Acid Diffusion ◽  
Nanoparticle Dispersions ◽  
Skin Explants ◽  
Cutaneous Administration

Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been loaded in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency and 200 nm mean dimension, as assessed by photon correlation spectroscopy. With the aim to improve the consistence of the aqueous nanodispersions, different types of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized by X-ray and rheological analyses. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was eight-fold slower with respect to the aqueous solution. In addition, the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective role exerted by the nanoparticles.

scholarly journals Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-β-Cyclodextrin Inclusion Complex †

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 531 ◽  
Author(s):  
Valentina Venuti ◽  
Vincenza Crupi ◽  
Barbara Fazio ◽  
Domenico Majolino ◽  
Giuseppe Acri ◽  
...  
Keyword(s):  
Fourier Transform ◽  
Inclusion Complex ◽  
Water Solubility ◽  
Ex Vivo ◽  
Morphological Changes ◽  
Physicochemical Characterization ◽  
Infrared Light ◽  
Phase Solubility ◽  
Theoretical Approaches

Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl-β-cyclodextrin (IDE/HP-β-CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, biological in vitro/ex vivo assays were performed. Phase solubility studies showed an AL type diagram, suggesting the presence of a 1:1 complex with high solubility. Scanning electron microscopy (SEM) allowed us to detect the morphological changes upon complexation. The intermolecular interactions stabilizing the inclusion complex were experimentally characterized by exploring the complementarity of Fourier-transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) with mid-infrared light, Fourier-transform near-infrared (FT-NIR) spectroscopy, and Raman spectroscopy. From the temperature evolution of the O–H stretching band of the complex, the average enthalpy ΔHHB of the hydrogen bond scheme upon inclusion was obtained. Two-dimensional (2D) rotating frame Overhauser effect spectroscopy (ROESY) analysis and computational studies involving molecular modeling and molecular dynamics (MD) simulation demonstrated the inclusion of the quinone ring of IDE inside the CD ring. In vitro/ex vivo studies evidenced that complexation produces a protective effect of IDE against the H2O2-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa.

NMR Studies of the Inclusion Complexes Between Ezetimibe and Cyclodextrins

2018 ◽  
Vol 69 (7) ◽  
pp. 1838-1841
Author(s):  
Hajnal Kelemen ◽  
Angella Csillag ◽  
Bela Noszal ◽  
Gabor Orgovan
Keyword(s):  
Inclusion Complex ◽  
Inclusion Complexes ◽  
Water Solubility ◽  
Solution Nmr ◽  
Spectroscopic Techniques ◽  
Nmr Studies ◽  
The Poor ◽  
Poor Water Solubility

Ezetimibe, the antihyperlipidemic drug of poor bioavailability was complexed with native and derivatized cyclodextrins.The complexes were characterized in terms stability, stoichiometry and structure using various 1D and 2D solution NMR spectroscopic techniques. The complexes were found to be of moderate stability (logK[3). The least stable inclusion complex is formed with b-cyclodextrin, while the ezetimibe-methylated-b--cyclodextrin has a 7-fold higher stability. The results can be useful to improve the poor water-solubility and the concomitant bioavailability of ezetimibe.

Formulation, Optimization,and Ex-Vivo Evaluation of Novel Lipid Carriers for Enhanced Transdermal Delivery of Hydroquinone

2020 ◽  
Vol 12 ◽  
Author(s):  
Shivani Verma ◽  
Sukhjinder Kaur ◽  
Lalit Kumar
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
Topical Delivery ◽  
Gelling Agent ◽  
Minimum Size ◽  
Prolonged Release ◽  
Freeze Dried ◽  
Ft Ir ◽  
Ir Analysis ◽  
Skin Retention

Background: HQ is used for hyper-pigmentation treatment using conventional creams and gels. These formulations show various disadvantages like poor skin permeation, allergic reactions, and repeated use decreasing patient compliance. Objectives: The present work involved formulation, statistical optimization, and characterization of nanostructured lipid carriers (NLCs) for efficient topical delivery of hydroquinone (HQ) for hyperpigmentation treatment. Methods: The NLCs were optimized exploring Box–Behnken design (BBD) using three independent variables and two dependent variables. Formulation having the minimum size and maximum drug entrapment was considered as optimized formulation. Optimized formulation was evaluated for drug release followed by its freeze-drying. The freeze-dried formulation was subjected to differential scanning calorimetry (DSC) analysis, X-raydiffraction (XRD) analysis, and Fourier transform-infrared spectroscopy (FT-IR) analysis. Furthermore, NLCs based gel was prepared by using Carbopol 934 as a gelling agent. NLCs based gel was evaluated for skin permeation, skin retention, and skin distribution (through confocal microscopic analysis) using pig ear skin. Results: Optimized NLCs showed smaller particle size [(271.9 ± 9) nm], high drug entrapment [(66.4 ± 1.2) %], tolerable polydispersity index (PDI) (0.221 ± 0.012), and zeta potential [(-25.9± 1.2) mV]. The FT-IR analysis revealed excellent compatibility between HQ and other excipients. The Carbopol 934 gel containing NLCs showed high transdermal flux [(163 ± 16.2) μg/cm2/h], permeability coefficient (0.0326 ± 0.0016), and skin permeation enhancement ratio (3.7 ± 0.4) compared to marketed cream of HQ. The results of confocal microscopic (CLSM) analysis revealed the accumulation of optimized NLCs in the lower epidermal layers of skin. Conclusion: NLCs based gel was considered effective in the topical delivery of HQ to treat hyper-pigmentation due high skin permeation, skin retention, and prolonged release of HQ.

scholarly journals Curcuma Longa, the “Golden Spice” to Counteract Neuroinflammaging and Cognitive Decline—What Have We Learned and What Needs to Be Done

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1519
Author(s):  
Alessandra Berry ◽  
Barbara Collacchi ◽  
Roberta Masella ◽  
Rosaria Varì ◽  
Francesca Cirulli
Keyword(s):  
Molecular Structure ◽  
Cognitive Decline ◽  
Neurodegenerative Disorders ◽  
Natural Compound ◽  
Water Solubility ◽  
Current Knowledge ◽  
Curcuma Longa ◽  
Biomedical Literature ◽  
Global Increase ◽  
New Strategies

Due to the global increase in lifespan, the proportion of people showing cognitive impairment is expected to grow exponentially. As target-specific drugs capable of tackling dementia are lagging behind, the focus of preclinical and clinical research has recently shifted towards natural products. Curcumin, one of the best investigated botanical constituents in the biomedical literature, has been receiving increased interest due to its unique molecular structure, which targets inflammatory and antioxidant pathways. These pathways have been shown to be critical for neurodegenerative disorders such as Alzheimer’s disease and more in general for cognitive decline. Despite the substantial preclinical literature on the potential biomedical effects of curcumin, its relatively low bioavailability, poor water solubility and rapid metabolism/excretion have hampered clinical trials, resulting in mixed and inconclusive findings. In this review, we highlight current knowledge on the potential effects of this natural compound on cognition. Furthermore, we focus on new strategies to overcome current limitations in its use and improve its efficacy, with attention also on gender-driven differences.

Preclinical Assessment of Nanostructured Liquid Crystalline Particles for the Management of Bacterial Keratitis: in-vivo and Pharmacokinetics Study

2021 ◽  
Author(s):  
Shreya Kaul ◽  
Upendra Nagaich ◽  
Navneet Verma
Keyword(s):  
Residence Time ◽  
Liquid Crystalline ◽  
Ex Vivo ◽  
Research Work ◽  
Poloxamer 407 ◽  
Pharmacokinetic Studies ◽  
Eye Drops ◽  
Statistical Experimental Design ◽  
Bacterial Keratitis

Abstract The research work was driven to develop novel nanostructured liquid crystalline particles of vancomycin for its improved pre-ocular residence time, ocular bio-availability, enhanced targeting, increased permeability, reduced dosing frequency, controlled drug release and reduced systemic side-effects. Formulation was developed by fragmenting cubic crystalline phase of glycerol monooleate, water and poloxamer 407. A four-factor, three-level Taguchi statistical experimental design was constructed to optimize the formulation. Formulations exhibited internal-cubic structure of the vesicles with particle size in the range of 51.11 ± 0.96 nm to 158.73 ± 0.46 nm and negative zeta potential. Ex-vivo transcorneal permeation studies demonstrated that the optimized cubosomes had 2.4-fold increase in apparent permeability co-efficient as compared to vancomycin solution. Whereas, in-vivo studies in rabbits demonstrated that the severity of keratitis was considerably lowered in day 3 with optimized cubosomes. Ocular pharmacokinetic studies evaluated level of drug in aqueous humor and results revealed that the time to peak concentration (Tmax) of vancomycin loaded cubosomal formulation was about 1.9-fold higher and mean residence time was 2.2-fold greater than vancomycin solution. Furthermore, histological examination revealed that the corneal layers displayed well-maintained morphology without any stromal swelling, consequently indicating safety of formulation. In conclusion, results manifested that the developed vancomycin loaded cubosomes could be a promising novel ocular carrier and an ideal substitute for conventional eye-drops for the management of bacterial-keratitis.

scholarly journals Novel polymeric micelles for insect pest control: encapsulation of essential oil monoterpenes inside a triblock copolymer shell for head lice control

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3171 ◽  
Author(s):  
Alejandro Lucia ◽  
Ariel Ceferino Toloza ◽  
Eduardo Guzmán ◽  
Francisco Ortega ◽  
Ramón G. Rubio
Keyword(s):  
Essential Oil ◽  
Pest Control ◽  
Polymeric Micelles ◽  
Ex Vivo ◽  
Insect Pest ◽  
Immersion Test ◽  
Poloxamer 407 ◽  
Head Lice ◽  
Hydrophobic Core ◽  
Micellar Systems

BackgroundEssential oil components (EOCs) are molecules with interesting application in pest control, these have been evaluated against different insect pest from more than 100 years, but their practical use is rather limited. Thus, the enhancement of their bioavailability and manageability due to their dispersion in water can open new perspective for the preparation of formulations for the control of insect pest. In this work, we studied the encapsulation of different monoterpenes in a poloxamer shell in order to prepare aqueous formulations that can be used for the development of platforms used in pest control.MethodsMicellar systems containing a 5 wt% of poloxamer 407 and 1.25 wt% of the different monoterpenes were prepared. Dynamic Light Scattering (DLS) experiments were carried out to characterize the dispersion of the EOCs in water. The pediculicidal activity of these micellar systems was tested on head lice using anex vivoimmersion test.ResultsThe poloxamers allowed the dispersion of EOCs in water due to their encapsulation inside the hydrophobic core of the copolymer micelles. From this study, we concluded that it is possible to make stable micellar systems containing water (>90 wt%), 1.25 wt% of different monoterpenes and a highly safe polymer (5wt% Poloxamer 407). These formulations were effective against head lice with mortality ranging from 30 to 60%, being the most effective emulsions those containing linalool, 1,8-cineole,α-terpineol, thymol, eugenol, geraniol and nonyl alcohol which lead to mortalities above 50%.DiscussionSince these systems showed good pediculicidal activity and high physicochemical stability, they could be a new route for the green fabrication of biocompatible and biosustainable insecticide formulations.

scholarly journals Improvement of Imiquimod Solubilization and Skin Retention via TPGS Micelles: Exploiting the Co-Solubilizing Effect of Oleic Acid

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1476
Author(s):  
Martina Ghezzi ◽  
Silvia Pescina ◽  
Andrea Delledonne ◽  
Ilaria Ferraboschi ◽  
Cristina Sissa ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Water Solubility ◽  
Skin Penetration ◽  
Water Soluble ◽  
Drug Solubility ◽  
Two Photon Microscopy ◽  
Skin Delivery ◽  
Polyethylene Glycol 1000 ◽  
The One ◽  
Skin Retention

Imiquimod (IMQ) is an immunostimulant drug approved for the topical treatment of actinic keratosis, external genital-perianal warts as well as superficial basal cell carcinoma that is used off-label for the treatment of different forms of skin cancers, including some malignant melanocytic proliferations such as lentigo maligna, atypical nevi and other in situ melanoma-related diseases. Imiquimod skin delivery has proven to be a real challenge due to its very low water-solubility and reduced skin penetration capacity. The aim of the work was to improve the drug solubility and skin retention using micelles of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of vitamin E, co-encapsulating various lipophilic compounds with the potential ability to improve imiquimod affinity for the micellar core, and thus its loading into the nanocarrier. The formulations were characterized in terms of particle size, zeta potential and stability over time and micelles performance on the skin was evaluated through the quantification of imiquimod retention in the skin layers and the visualization of a micelle-loaded fluorescent dye by two-photon microscopy. The results showed that imiquimod solubility strictly depends on the nature and concentration of the co-encapsulated compounds. The micellar formulation based on TPGS and oleic acid was identified as the most interesting in terms of both drug solubility (which was increased from few µg/mL to 1154.01 ± 112.78 µg/mL) and micellar stability (which was evaluated up to 6 months from micelles preparation). The delivery efficiency after the application of this formulation alone or incorporated in hydrogels showed to be 42- and 25-folds higher than the one of the commercial creams.

scholarly journals Preparation, Characterization, and Bioavailability of Host-Guest Inclusion Complex of Ginsenoside Re with Gamma-Cyclodextrin

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7227
Author(s):  
Hui Li ◽  
Guolei Zhang ◽  
Wei Wang ◽  
Changbao Chen ◽  
Lili Jiao ◽  
...  
Keyword(s):  
Inclusion Complex ◽  
Water Solubility ◽  
Area Under The Curve ◽  
Relative Bioavailability ◽  
Docking Studies ◽  
Solubility Parameters ◽  
Phase Solubility ◽  
Scanning Calorimetry ◽  
Ginsenoside Re

This work aimed at improving the water solubility of Ginsenoside (G)-Re by forming an inclusion complex. The solubility parameters of G-Re in alpha (α), beta (β), and gamma (γ) cyclodextrin (CD) were investigated. The phase solubility profiles were all classified as AL-type that indicated the 1:1 stoichiometric relationship with the stability constants Ks which were 22 M−1 (α-CD), 612 M−1 (β-CD), and 14,410 M−1 (γ-CD), respectively. Molecular docking studies confirmed the results of phase solubility with the binding energy of −4.7 (α-CD), −5.10 (β-CD), and −6.70 (γ-CD) kcal/mol, respectively. The inclusion complex (IC) of G-Re was prepared with γ-CD via the water-stirring method followed by freeze-drying. The successful preparation of IC was confirmed by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In-vivo absorption studies were carried out by LC-MS/MS. Dissolution rate of G-Re was increased 9.27 times after inclusion, and the peak blood concentration was 2.7-fold higher than that of pure G-Re powder. The relative bioavailability calculated from the ratio of Area under the curve AUC0–∞ of the inclusion to pure G-Re powder was 171%. This study offers the first report that describes G-Re’s inclusion into γ-CD, and explored the inclusion complex’s mechanism at the molecular level. The results indicated that the solubility could be significantly improved as well as the bioavailability, implying γ-CD was a very suitable inclusion host for complex preparation of G-Re.

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