scholarly journals Micelles of Progesterone for Topical Eye Administration: Interspecies and Intertissues Differences in Ex Vivo Ocular Permeability

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 702 ◽  
Author(s):  
Adrián M. Alambiaga-Caravaca ◽  
María Aracely Calatayud-Pascual ◽  
Vicent Rodilla ◽  
Angel Concheiro ◽  
Alicia López-Castellano ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Chorioallantoic Membrane ◽  
Aqueous Solubility ◽  
Pluronic F68 ◽  
Drug Permeability ◽  
Low Viscosity ◽  
Hen’S Egg ◽  
Ocular Bioavailability ◽  
In Situ Gelling

Progesterone (PG) may provide protection to the retina during retinitis pigmentosa, but its topical ocular supply is hampered by PG poor aqueous solubility and low ocular bioavailability. The development of efficient topical ocular forms must face up to two relevant challenges: Protective barriers of the eyes and lack of validated ex vivo tests to predict drug permeability. The aims of this study were: (i) To design micelles using Pluronic F68 and Soluplus copolymers to overcome PG solubility and permeability; and (ii) to compare drug diffusion through the cornea and sclera of three animal species (rabbit, porcine, and bovine) to investigate interspecies differences. Micelles of Pluronic F68 (3–4 nm) and Soluplus (52–59 nm) increased PG solubility by one and two orders of magnitude, respectively and exhibited nearly a 100% encapsulation efficiency. Soluplus systems showed in situ gelling capability in contrast to the low viscosity Pluronic F68 micelles. The formulations successfully passed the hen’s egg-chorioallantoic membrane test (HET-CAM) test. PG penetration through rabbit cornea and sclera was faster than through porcine or bovine cornea, although the differences were also formulation-dependent. Porcine tissues showed intermediate permeability between rabbit and bovine. Soluplus micelles allowed greater PG accumulation in cornea and sclera whereas Pluronic F68 promoted a faster penetration of lower PG doses.

scholarly journals Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin

Nanomaterials ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 745 ◽  
Author(s):  
Blanca Lorenzo-Veiga ◽  
Hakon Hrafn Sigurdsson ◽  
Thorsteinn Loftsson ◽  
Carmen Alvarez-Lorenzo
Keyword(s):  
Mixed Micelles ◽  
Water Solubility ◽  
Ex Vivo ◽  
Chorioallantoic Membrane ◽  
Ex Vivo Permeation ◽  
Hen’S Egg ◽  
Permeation Studies ◽  
20 Nm ◽  
In Situ Gelling

Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. Soluplus and Pluronic P103 dispersions were prepared in 0.9% NaCl and pH 6.4 buffer, with or without α-cyclodextrin (αCD; 10% w/v), and characterized through particle size, zeta potential, solubilization efficiency, rheological properties, ocular tolerance, in vitro drug diffusion, and ex vivo permeation studies. Soluplus micelles (90–103 nm) and mixed micelles (150–110 nm) were larger than Pluronic P103 ones (16–20 nm), but all showed zeta potentials close to zero. Soluplus, Pluronic P103, and their mixed micelles increased natamycin solubility up to 6.00-fold, 3.27-fold, and 2.77-fold, respectively. Soluplus dispersions and poly(pseudo)rotaxanes exhibited in situ gelling capability, and they transformed into weak gels above 30 °C. All the formulations were non-irritant according to Hen’s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay. Poly(pseudo)rotaxanes facilitated drug accumulation into the cornea and sclera, but led to lower natamycin permeability through the sclera than the corresponding micelles. Poly(pseudo)rotaxanes made from mixed micelles showed intermediate natamycin diffusion coefficients and permeability values between those of Pluronic P103-based and Soluplus-based poly(pseudo)rotaxanes. Therefore, the preparation of mixed micelles may be a useful tool to regulate drug release and enhance ocular permeability.

scholarly journals Investigating the ocular toxicity potential and therapeutic efficiency of in situ gel nanoemulsion formulations of brinzolamide

2020 ◽  
Vol 9 (4) ◽  
pp. 578-587
Author(s):  
Sima Talaei ◽  
Mohammad Mehdi Mahboobian ◽  
Mojdeh Mohammadi
Keyword(s):  
Intraocular Pressure ◽  
Membrane Surface ◽  
Chorioallantoic Membrane ◽  
In Situ Gel ◽  
Toxicity Potential ◽  
Vessel Injury ◽  
Hen’S Egg

Abstract Glaucoma is an ocular disease i.e. more common in older adults with elevated intraocular pressure and a serious threat to vision if it is not controlled. Due to the limitations regarding the conventional form of brinzolamide (Azopt®), two optimum formulations of in situ gel nanoemulsion were developed. To ensure the safety and efficacy of developed formulations for ocular drug delivery, the current study was designed. MTT assay was carried out on the human retinal pigmentation epithelial cells. To investigate the irritation potential of the chosen formulations, hen’s egg test-chorioallantoic membrane as a borderline test between in vivo and in vitro methods has been done. The modified Draize method was utilized to evaluate eye tolerance against the selected formulations. Intraocular pressure was measured by applying the prepared formulations to the eyes of normotensive albino rabbits in order to assess the therapeutic efficacy. Based on MTT test, cell viability for NE-2 at 0.1% and NE-1 at 0.1 and 0.5% concentrations was acceptable. The results of the hen’s egg test-chorioallantoic membrane test indicated no sign of vessel injury on the chorioallantoic membrane surface for both formulations. Also, during 24 h, both formulations were well-tolerated by rabbit eyes. The pharmacodynamics effects of formulations had no difference or were even higher than that of suspension in case of adding lower concentration (0.5%) of brinzolamide to the formulations. With regard to the results of the mentioned methods, our advanced formulations were effective, safe, and well-tolerated, thus can be introduced as an appropriate vehicle for ocular delivery of brinzolamide.

scholarly journals DEVELOPMENT AND EVALUATION OF A POLOXAMER- AND CHITOSAN-BASED IN SITU GEL-FORMING INJECTABLE DEPOT

2020 ◽  
pp. 36-41
Author(s):  
Hema a Nair ◽  
NAZIA BEGUM
Keyword(s):  
Ex Vivo ◽  
Gelation Time ◽  
In Vitro Release ◽  
Aqueous Acetic Acid ◽  
Drug Content ◽  
Low Viscosity ◽  
Model Drug ◽  
Dialysis Bag

Objective: The present study is intended to investigate the applicability of poloxamer- and chitosan-based temperature induced in situ injectable gelling depot for once a week therapy as an intramuscular injection employing olanzapine as a model drug. Methods: The thermosetting gel was prepared by admixture of a solution of poloxamer P127 and a solution of olanzapine and chitosan in aqueous acetic acid. The resultant formulation was characterized for gelation temperature, gelation time, viscosity, syringeability, pH, drug content, and in vitro drug release. The in vitro release of olanzapine from the gelled depot was followed using USP paddle type II apparatus in conjunction with a dialysis bag. The gel was injected ex vivo into chicken muscle and observed by subsequent dissection. Results: The formulation was designed to have a phase transition temperature of 34°C and gelled in <10 s at 37°C. Addition of chitosan imparted favorable rheological properties to the poloxamer gel and resulted in a pseudoplastic mixture with low viscosity in the sol state and higher viscosity post gelation. The preparation had a pH of 5.4, appropriate drug content and readily passed through a 20 gauge needle. The release of olanzapine was unhindered by the dialysis bag. Following an initial bust, a sustained, zero-order release of the remainder of drug was observed up to 9 days. The injectable was found to form a compact depot when evaluated ex vivo. Conclusion: The developed system showed several features which make it a suitable vehicle for sustained intramuscular delivery of drugs.

In vitro and ex vivo characterisation of an in situ gelling formulation for sustained lidocaine release with potential use following knee arthroplasty

2018 ◽  
Vol 8 (3) ◽  
pp. 820-829 ◽  
Author(s):  
Manisha Sharma ◽  
Kaushik Chandramouli ◽  
Louise Curley ◽  
Beau Pontre ◽  
Keryn Reilly ◽  
...  
Keyword(s):  
Knee Arthroplasty ◽  
Ex Vivo ◽  
In Situ Gelling ◽  
Potential Use

scholarly journals Development of a Mucoadhesive and In Situ Gelling Formulation Based on κ-Carrageenan for Application on Oral Mucosa and Esophagus Walls. I. A Functional In Vitro Characterization

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 112 ◽  
Author(s):  
Barbara Vigani ◽  
Angela Faccendini ◽  
Silvia Rossi ◽  
Giuseppina Sandri ◽  
Maria Bonferoni ◽  
...  
Keyword(s):  
Oral Mucositis ◽  
Protective Action ◽  
Rheological Characterization ◽  
Low Viscosity ◽  
In Vitro Characterization ◽  
Biological Substrates ◽  
Clinically Significant ◽  
In Situ Gelling

Oral mucositis and esophagitis represent the most frequent and clinically significant complications of cytoreductive chemotherapy and radiotherapy, which severely compromise the patient quality of life. The local application of polymeric gels could protect the injured tissues, alleviating the most painful symptoms. The present work aims at developing in situ gelling formulations for the treatment of oral mucositis and esophagitis. To reach these targets, κ-carrageenan (κ-CG) was selected as a polymer having wound healing properties and able to gelify in the presence of saliva ions, while hydroxypropyl cellulose (HPC) was used to improve the mucoadhesive properties of the formulations. CaCl2 was identified as a salt able to enhance the interaction between κ-CG and saliva ions. Different salt and polymer concentrations were investigated in order to obtain a formulation having the following features: (i) low viscosity at room temperature to facilitate administration, (ii) marked elastic properties at 37 °C, functional to a protective action towards damaged tissues, and (iii) mucoadhesive properties. Prototypes characterized by different κ-CG, HPC, and CaCl2 concentrations were subjected to a thorough rheological characterization and to in vitro mucoadhesion and washability tests. The overall results pointed out the ability of the developed formulations to produce a gel able to interact with saliva ions and to adhere to the biological substrates.

scholarly journals In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery

2016 ◽  
Vol 502 (1-2) ◽  
pp. 70-79 ◽  
Author(s):  
Kosai Al Khateb ◽  
Elvira K. Ozhmukhametova ◽  
Marat N. Mussin ◽  
Serzhan K. Seilkhanov ◽  
Tolebai K. Rakhypbekov ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ocular Drug Delivery ◽  
Pluronic F127 ◽  
Pluronic F68 ◽  
In Situ Gelling

In vivo study of hypericin-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system in a mice model of vulvovaginal candidiasis

2021 ◽  
Author(s):  
Patricia Rocha de Araújo ◽  
Giovana Maria Fioramonti Calixto ◽  
Victor Hugo Sousa Araújo ◽  
Mariana Rillo Sato ◽  
Camila Fernanda Rodero ◽  
...  
Keyword(s):  
Liquid Crystalline ◽  
Ex Vivo ◽  
Vulvovaginal Candidiasis ◽  
Poloxamer 407 ◽  
Vaginal Fluid ◽  
Vaginal Mucosa ◽  
Ex Vivo Permeation ◽  
In Situ Gelling

Abstract The present study reports the performance of the pigment hypericin (HYP)-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system (LCPS) for the treatment of vulvovaginal candidiasis (VVC) in mice. LCPS composed of 40% of ethoxylated and propoxylated cetyl alcohol, 30% of oleic acid and cholesterol (7:1), 30% of a dispersion of 16% poloxamer 407 and 0.05% of HYP (HYP-LCPS) was prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and ex vivo permeation and retention studies across vaginal porcine mucosa were performed. In addition, the antifungal properties of the HYP-LCPS were evaluated in a murine in vivo model; for this, infected C57BL female mice groups were treated with both HYP in solution and HYP-LCPS, and after 6 days colony forming unit (CFU)/ml count was performed. PLM and SAXS confirmed that HYP-LCPS is a microemulsion situated in boundary transition region confirming its action as an LCPS. When in contact with simulated vaginal fluid, HYP-LCPS became rigid and exhibited maltase crosses and bragg peaks characteristics of lamellar phase. Ex vivo permeation and retention studies showed that HYP-LCPS provides a localized treatment on the superficial layers of porcine vaginal mucosa. HYP-LCPS induced a significant reduction in the number of CFU/ml in the mice; thus this formulation indicated it is as effective as a commercial dosage form. It was concluded that LCPS maintains the biological activity of HYP and provides an adequate drug delivery system for this lipophilic molecule at the vaginal mucosa, being a promising option in cases of VVC.

scholarly journals A Novel Gel-Forming Solution Based on PEG-DSPE/Solutol HS 15 Mixed Micelles and Gellan Gum for Ophthalmic Delivery of Curcumin

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 81 ◽  
Author(s):  
Na Sai ◽  
Xiaoxv Dong ◽  
Pingqing Huang ◽  
Longtai You ◽  
Chunjing Yang ◽  
...  
Keyword(s):  
Mixed Micelles ◽  
Ex Vivo ◽  
Aqueous Solubility ◽  
Gellan Gum ◽  
Pseudoplastic Fluid ◽  
Ophthalmic Delivery ◽  
Ophthalmic Drug ◽  
Solutol Hs 15 ◽  
In Situ Gelling ◽  
Labeling Method

Curcumin (Cur) is a naturally hydrophobic polyphenol with potential pharmacological properties. However, the poor aqueous solubility and low bioavailability of curcumin limits its ocular administration. Thus, the aim of this study was to prepare a mixed micelle in situ gelling system of curcumin (Cur-MM-ISG) for ophthalmic drug delivery. The curcumin mixed micelles (Cur-MMs) were prepared via the solvent evaporation method, after which they were incorporated into gellan gum gels. Characterization tests showed that Cur-MMs were small in size and spherical in shape, with a low critical micelle concentration. Compared with free curcumin, Cur-MMs improved the solubility and stability of curcumin significantly. The ex vivo penetration study revealed that Cur-MMs could penetrate the rabbit cornea more efficiently than the free curcumin. After dispersing the micelles in the gellan gum solution at a ratio of 1:1 (v/v), a transparent Cur-MM-ISG with the characteristics of a pseudoplastic fluid was formed. No obvious irritations were observed in the rabbit eyes after ocular instillation of Cur-MM-ISG. Moreover, Cur-MM-ISG showed a longer retention time on the corneal surface when compared to Cur-MMs using the fluorescein sodium labeling method. These findings indicate that biocompatible Cur-MM-ISG has great potential in ophthalmic drug therapy.

scholarly journals Resveratrol-Loaded Hydrogel Contact Lenses with Antioxidant and Antibiofilm Performance

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 532
Author(s):  
María Vivero-Lopez ◽  
Andrea Muras ◽  
Diana Silva ◽  
Ana Paula Serro ◽  
Ana Otero ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Contact Lenses ◽  
Ex Vivo ◽  
Chorioallantoic Membrane ◽  
Preferential Adsorption ◽  
Ocular Infections ◽  
Silicone Hydrogels ◽  
Hen’S Egg ◽  
Wide Range ◽  
And Staphylococcus Aureus

Contact lenses (CLs) are prone to biofilm formation, which may cause severe ocular infections. Since the use of antibiotics is associated with resistance concerns, here, two alternative strategies were evaluated to endow CLs with antibiofilm features: copolymerization with the antifouling monomer 2-methacryloyloxyethyl phosphorylcholine (MPC) and loading of the antioxidant resveratrol with known antibacterial activity. MPC has, so far, been used to increase water retention on the CL surface (Proclear® 1 day CLs). Both poly(hydroxyethyl methacrylate) (HEMA) and silicone hydrogels were prepared with MPC covering a wide range of concentrations (from 0 to 101 mM). All hydrogels showed physical properties adequate for CLs and successfully passed the hen’s egg-chorioallantoic membrane (HET-CAM) test. Silicone hydrogels had stronger affinity for resveratrol, with higher loading and a slower release rate. Ex vivo cornea and sclera permeability tests revealed that resveratrol released from the hydrogels readily accumulated in both tissues but did not cross through. The antibiofilm tests against Pseudomonas aeruginosa and Staphylococcus aureus evidenced that, in general, resveratrol decreased biofilm formation, which correlated with its concentration-dependent antibacterial capability. Preferential adsorption of lysozyme, compared to albumin, might also contribute to the antimicrobial activity. In addition, importantly, the loading of resveratrol in the hydrogels preserved the antioxidant activity, even against photodegradation. Overall, the designed hydrogels can host therapeutically relevant amounts of resveratrol to be sustainedly released on the eye, providing antibiofilm and antioxidant performance.

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