scholarly journals Hyaluronan-Cholesterol Nanogels for the Enhancement of the Ocular Delivery of Therapeutics

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1781
Author(s):  
Nicole Zoratto ◽  
Laura Forcina ◽  
Roberto Matassa ◽  
Luciana Mosca ◽  
Giuseppe Familiari ◽  
...  
Keyword(s):  
Water Solubility ◽  
Ex Vivo ◽  
Diclofenac Sodium ◽  
Free Drug ◽  
Hydrophobic Drugs ◽  
Permeation Enhancers ◽  
Hydrophilic Drugs ◽  
Anatomy And Physiology ◽  
Ocular Disorders ◽  
Ocular Bioavailability

The anatomy and physiology of the eye strongly limit the bioavailability of locally administered drugs. The entrapment of therapeutics into nanocarriers represents an effective strategy for the topical treatment of several ocular disorders, as they may protect the embedded molecules, enabling drug residence on the ocular surface and/or its penetration into different ocular compartments. The present work shows the activity of hyaluronan-cholesterol nanogels (NHs) as ocular permeation enhancers. Thanks to their bioadhesive properties, NHs firmly interact with the superficial corneal epithelium, without penetrating the stroma, thus modifying the transcorneal penetration of loaded therapeutics. Ex vivo transcorneal permeation experiments show that the permeation of hydrophilic drugs (i.e., tobramycin and diclofenac sodium salt), loaded in NHs, is significantly enhanced when compared to the free drug solutions. On the other side, the permeation of hydrophobic drugs (i.e., dexamethasone and piroxicam) is strongly dependent on the water solubility of the entrapped molecules. The obtained results suggest that NHs formulations can improve the ocular bioavailability of the instilled drugs by increasing their preocular retention time (hydrophobic drugs) or facilitating their permeation (hydrophilic drugs), thus opening the route for the application of HA-based NHs in the treatment of both anterior and posterior eye segment diseases.

scholarly journals Hyaluronan-Cholesterol Nanogels for the Enhancement of the Ocular Delivery of Therapeutics

2021 ◽  
Author(s):  
Nicole Zoratto ◽  
Laura Forcina ◽  
Roberto Matassa ◽  
Luciana Mosca ◽  
Giuseppe Familiari ◽  
...  
Keyword(s):  
Water Solubility ◽  
Ex Vivo ◽  
Diclofenac Sodium ◽  
Free Drug ◽  
Hydrophobic Drugs ◽  
Permeation Enhancers ◽  
Hydrophilic Drugs ◽  
Anatomy And Physiology ◽  
Ocular Disorders ◽  
Ocular Bioavailability

The anatomy and physiology of the eye strongly limit the bioavailability of locally administered drugs. The entrapment of therapeutics into nanocarriers represents an effective strategy to topically treat some ocular disorders, as they may protect the entrapped molecules, facilitating drug residence on the ocular surface and/or its penetration into different ocular compartments. The present work shows the activity of hyaluronan-cholesterol nanogels (NHs) as ocular permeation enhancers. Thanks to their bioadhesive properties, NHs firmly interact with the superficial corneal epithelium, without penetrating the stroma, modifying the transcorneal penetration of loaded therapeutics. Ex-vivo transcorneal permeation experiments showed that the permeation of hydrophilic drugs (i.e. tobramycin and diclofenac sodium salt), loaded in NHs, is significantly enhanced when compared to the free drug solutions. On the other side the permeation of hydrophobic drugs (i.e. dexamethasone and piroxicam) is strongly dependent on the water solubility of the entrapped molecules. The obtained results suggest that NHs formulations can improve the ocular bioavailability of the instilled drugs by increasing their preocular retention time (hydrophobic drugs) or facilitating their permeation (hydrophilic drugs), thus opening the route for the application of HA-based NHs in the treatment of both anterior and posterior eye segment diseases.

scholarly journals Biopharmaceutical Assessment of Dexamethasone Acetate-Based Hydrogels Combining Hydroxypropyl Cyclodextrins and Polysaccharides for Ocular Delivery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 717 ◽  
Author(s):  
Roseline Mazet ◽  
Xurxo García-Otero ◽  
Luc Choisnard ◽  
Denis Wouessidjewe ◽  
Vincent Verdoot ◽  
...  
Keyword(s):  
Water Solubility ◽  
Ex Vivo ◽  
Cytotoxic Effects ◽  
Corneal Epithelial ◽  
Pet Ct ◽  
Dexamethasone Acetate ◽  
Mixture Designs ◽  
Ocular Bioavailability

We previously developed two optimized formulations of dexamethasone acetate (DXMa) hydrogels by means of special cubic mixture designs for topical ocular administration. These gels were elaborated with hydroxypropyl-β-CD (HPβCD) and hydroxypropyl-γ-CD (HPγCD) and commercial hydrogels in order to enhance DXMa water solubility and finally DXMa’s ocular bioavailability and transcorneal penetration. The main objective of this study was to characterize them and to evaluate in vitro, ex vivo, and in vivo their safety, biopermanence, and transcorneal permeation. Gels A and B are Newtonian fluids and display a viscosity of 13.2 mPa.s and 18.6 mPa.s, respectively, which increases their ocular retention, according to the in vivo biopermanence study by PET/CT. These hydrogels could act as corneal absorption promoters as they allow a higher transcorneal permeation of DXMa through porcine excised cornea, compared to DEXAFREE® and MAXIDEX®. Cytotoxicity assays showed no cytotoxic effects on human primary corneal epithelial cells (HCE). Furthermore, Gel B is clearly safe for the eye, but the effect of Gel A on the human eye cannot be predicted. Both gels were also stable 12 months at 25 °C after sterilization by filtration. These results demonstrate that the developed formulations present a high potential for the topical ocular administration of dexamethasone acetate.

Chemical Permeation Enhancers for Transdermal Delivery of Thiocolchicoside: Assessment of Ex-vivo Skin Flux and In-vivo Pharmacokinetics

2017 ◽  
Vol 10 (5) ◽  
pp. 3827-3835
Author(s):  
Y Madhusudan Rao ◽  
Gayatri P ◽  
Ajitha M ◽  
P. Pavan Kumar ◽  
Kiran kumar
Keyword(s):  
Passive Control ◽  
Ex Vivo ◽  
Skin Permeation ◽  
In Vivo Studies ◽  
Permeation Enhancers ◽  
Casting Technique ◽  
Chemical Permeation Enhancers ◽  
Chemical Permeation ◽  
In Vivo Pharmacokinetics

Present investigation comprises the study of ex-vivo skin flux and in-vivo pharmacokinetics of Thiocolchicoside (THC) from transdermal films. The films were fabricated by solvent casting technique employing combination of hydrophilic and hydrophobic polymers. A flux of 18.08 µg/cm2h and 13.37µg/cm2h was achieved for optimized formulations containing 1, 8-cineole and oleic acid respectively as permeation enhancers. The observed flux values were higher when compared to passive control (8.66 µg/cm2h). Highest skin permeation was observed when 1,8-cineole was used as chemical permeation enhancer and it considerably (2-2.5 fold) improved the THC transport across the rat skin. In vivo studies were performed in rabbits and samples were analysed by LC-MS-MS. The mean area under the curve (AUC) values of transdermal film showed about 2.35 times statistically significant (p<0.05) improvement in bioavailability when compared with the oral administration of THC solution. The developed transdermal therapeutic systems using chemical permeation enhancers were suitable for drugs like THC in effective management of muscular pain.    

scholarly journals A Micellar-Hydrogel Nanogrid from a UV Crosslinked Inulin Derivative for the Simultaneous Delivery of Hydrophobic and Hydrophilic Drugs

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 97 ◽  
Author(s):  
Delia Mandracchia ◽  
Adriana Trapani ◽  
Sara Perteghella ◽  
Cinzia Di Franco ◽  
Maria Torre ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Beclomethasone Dipropionate ◽  
Polymeric Micelles ◽  
Hydrophobic Drugs ◽  
Hydrophobic Drug ◽  
Hydrophilic Drugs ◽  
Uv Crosslinking ◽  
Colon Drug Delivery ◽  
Materials Used ◽  
Simultaneous Delivery

Hydrogels are among the most common materials used in drug delivery, as polymeric micelles are too. They, preferentially, load hydrophilic and hydrophobic drugs, respectively. In this paper, we thought to combine the favorable behaviors of both hydrogels and polymeric micelles with the specific aim of delivering hydrophilic and hydrophobic drugs for dual delivery in combination therapy, in particular for colon drug delivery. Thus, we developed a hydrogel by UV crosslinking of a methacrylated (MA) amphiphilic derivative from inulin (INU) (as known INU is specifically degraded into the colon) and vitamin E (VITE), called INVITEMA. The methacrylated micelles were physicochemically characterized and subjected to UV irradiation to form what we called the “nanogrids”. The INVITEMA nanogrids were characterized by DSC, SEM, TEM, water uptake and beclomethasone dipropionate (BDP) release. In particular, the release of the hydrophobic drug was specifically assessed to verify that it can spread along the hydrophilic portions and, therefore, effectively released. These systems can open new pharmaceutical applications for known hydrogels or micelle systems, considering that in literature only few examples are present.

Hydrophobically-modified gelatin hydrogel as a carrier for charged hydrophilic drugs and hydrophobic drugs

2020 ◽  
Vol 149 ◽  
pp. 140-147 ◽  
Author(s):  
Takayuki Takei ◽  
Ryosuke Yoshihara ◽  
So Danjo ◽  
Yoshiki Fukuhara ◽  
Courtney Evans ◽  
...  
Keyword(s):  
Hydrophobic Drugs ◽  
Hydrophilic Drugs ◽  
Gelatin Hydrogel ◽  
Hydrophobically Modified

scholarly journals NANOEMULSIONS FOR PROSTRATE CANCER THERAPY: AN OVERVIEW

2017 ◽  
Vol 10 (5) ◽  
pp. 37
Author(s):  
Manikandan P ◽  
Sundara Ganapathy R
Keyword(s):  
Prostate Cancer ◽  
Oral Delivery ◽  
Water Solubility ◽  
Oral Absorption ◽  
Solid Dispersions ◽  
Dose Proportionality ◽  
Permeation Enhancers ◽  
Lipophilic Drugs ◽  
Prostrate Cancer ◽  
Gastric Fluids

The objective of this review is to focus the inferences of low/poor bioavailability and lack of dose proportionality for the oral delivery of drugs in prostatecancer therapy. To overcome such problems, various formulation strategies has been reported including various methods for the use of surfactants,cyclodextrins, solid dispersions, micronization, permeation enhancers, and lipids. Flutamide is an antiandrogen drug and used for the therapy of prostate cancer. The flutamide drug is having limited clinical application due to its poor water solubility and needs enhancement of its dissolution rate in simulated gastric fluids. The lipid-based formulations such as nanoemulsion have been shown to improve the solubility and oral absorption of lipophilic drugs. To conclude, this article emphasizes the various approaches of nanoemulsion based formulation for prostate cancer therapy.Keywords: Nanoemulsion, Prostate cancer, Flutamide, Antiandrogen drug, Lipophilic drugs.

scholarly journals Preparation, Characterization and Ex vivo Permeability Study of Transdermal Apixaban O/W Nanoemulsion Based Gel

2020 ◽  
Vol 29 (2) ◽  
pp. 214-222
Author(s):  
Mustafa R. Abdulbaqi ◽  
Nawal A.Rajab
Keyword(s):  
Water Solubility ◽  
Ex Vivo ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Good Method ◽  
Gelling Agent ◽  
Permeation Enhancer ◽  
Permeability Study ◽  
Anticoagulant Drug ◽  
Triton X

This study designed to prepare ultrafine apixaban (APX) o/w nanoemulsion (NE) based gel with droplet size below 50 nm as a good method for transdermal APX delivery without using permeation enhancer, alternatively, the formulation components itself act as permeation enhancer. APX, a potent oral anticoagulant drug that selectively and directly inhibit coagulation factor Xa, was selected as a good candidate for transdermal delivery as it displays poor water solubility (0.028 mg/mL) and low bioavailability (50%). APX-NE gel was prepared using triacetin, triton-x-100 and carbitol as oil phase, surfactant and cosurfactant respectively, while Carbopol 940 used as a gelling agent. Ex vivo permeation of APX-NE gel through human stratum corneum reveal

scholarly journals Engineering Human CNS Morphogenesis: Controlled Induction of Singular Neural Rosette Emergence

2017 ◽  
Author(s):  
Gavin T. Knight ◽  
Brady F. Lundin ◽  
Nisha Iyer ◽  
Lydia M.T. Ashton ◽  
William A. Sethares ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Pluripotent Stem Cell ◽  
Ex Vivo ◽  
Neural Tissue ◽  
Emergent Properties ◽  
Human Pluripotent Stem Cell ◽  
Biophysical Parameter ◽  
Anatomy And Physiology ◽  
Neural Tissues ◽  
Brain And Spinal Cord

AbstractHuman pluripotent stem cell (hPSC)-derived neural organoids have revolutionized in vitro modelling of human neurological disorders. Cell-intrinsic morphogenesis processes displayed within these tissues could serve as the basis for ex vivo manufacture of brain and spinal cord tissues with biomimetic anatomy and physiology. However, we must first understand how to control their emergent properties starting at the genesis of neural organoid formation, i.e. emergence of polarized neuroepithelium. In vivo, all CNS tissues develop from a singular neuroepithelial tube. Yet, current protocols yield organoids with multiple neuroepithelial rings, a.k.a. neural rosettes, each acting as independent centers of morphogenesis and thereby impeding coordinate tissue development. We discovered that the morphology of hPSC-derived neural tissues is a critical biophysical parameter for inducing singular neural rosette emergence. Tissue morphology screens conducted using micropatterned array substrates and an automated image analysis determined that circular morphologies of 200-250 and 150μm diameter are optimal for inducing singular neural rosette emergence within 80-85% forebrain and 73.5% spinal tissues, respectively. The discrepancy in optimal circular morphology for Pax6+/N-cadherin+ neuroepithelial forebrain versus spinal tissues was due to previously unknown differences in ROCK-mediated cell contractility. The singular neuroepithelium induced within geometrically confined tissues persisted as the tissues morphed from a 2-D monolayer to multilayered 3-D hemispherical aggregate. Upon confinement release using clickable micropatterned substrates, the tissue displayed radial outgrowth with maintenance of a singular neuroepithelium and peripheral neuronal differentiation. Thus, we have quantitatively defined a pertinent biophysical parameter for effectively inducing a singular neuroepithelium emergence within morphing hPSC-derived neural tissues.Significance StatementHuman pluripotent stem cell (hPSC)-derived neural organoids display emergent properties that, if harnessed, could serve as the basis for ex vivo manufacture of brain and spinal cord tissues with biomimetic macroscale anatomy and physiology. Their chaotic terminal structure arises from uncontrolled morphogenesis at their genesis, resulting in spontaneous induction of multiple neuroepithelial morphogenesis centers,a.k.a. neural rosettes. Here, we determined that neural tissue morphology is a pertinent biophysical parameter for controlling subsequent morphogenesis, and identified discrete circular tissue morphologies as optimal and effective at inducing singular neural rosette emergence within forebrain and spinal neural tissues. Thus, we developed an approach to reproducibly control the initial stage of hPSC-derived neural tissue morphogenesis enabling their manufacture with a biomimetic nascent CNS anatomy.

scholarly journals Potential Albumin-Based Antioxidant Nanoformulations for Ocular Protection against Oxidative Stress

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 297 ◽  
Author(s):  
Kim ◽  
Maharjan ◽  
Jin ◽  
Park ◽  
Maharjan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Epithelial Cells ◽  
Ursolic Acid ◽  
Water Solubility ◽  
Antioxidant Activities ◽  
Drug Efficacy ◽  
Topical Administration ◽  
Oxidative Stresses ◽  
Ophthalmic Drug ◽  
Ocular Bioavailability

Amongst various drug administration methods, ophthalmic drug delivery has been a useful way for the treatment of eye-related diseases. However, therapeutic efficacy of ocular therapy for anterior or posterior eye segments through topical administration is considerably challenged by the number of anatomical and physiological barriers in the eyes affecting ocular bioavailability. In this respect, advanced biocompatible nanoformulations make it possible to improve drug delivery to the target sites and enhance ocular bioavailability of ophthalmic medicines. Various ocular diseases have been reported to be related to oxidative stresses in tissues, and polyphenolic compounds have been known for their antioxidant activities in various tissues, including the eyes. Despite drug efficacy, poor water solubility and intrinsic color of the compounds limit the drug’s inclusion into the development of ocular medicine. In the present study, we investigated the antioxidant protectant efficacy of rosmarinic or ursolic acid in the retinal epithelial cells, as compared to those of curcumin, by forming nanospheres with bovine serum albumin. Our results demonstrate that antioxidant-containing nanoformulations provide a significantly higher drug solubility and decreased ROS (reactive oxygen species) production in the retinal epithelial cells. Finally, we also found that albumin-based nanoformulations could improve bioavailability and increase antioxidant activity of rosmarinic or ursolic acid in the retina to be applied as efficient ocular protectant.

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