scholarly journals Polymeric Micelles for the Enhanced Deposition of Hydrophobic Drugs into Ocular Tissues, without Plasma Exposure

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 744
Author(s):  
Ijeoma F. Uchegbu ◽  
Jan Breznikar ◽  
Alessandra Zaffalon ◽  
Uche Odunze ◽  
Andreas G. Schätzlein
Keyword(s):  
Polymeric Micelles ◽  
Rabbit Model ◽  
Penetration Enhancer ◽  
Hydrophobic Drugs ◽  
Ocular Tissues ◽  
Ocular Penetration ◽  
Self Assembling ◽  
Similar Dose ◽  
Oil In Water ◽  
The Stability

Commercial topical ocular formulations for hydrophobic actives rely on the use of suspensions or oil in water emulsions and neither of these formulation modalities adequately promote drug penetration into ocular tissues. Using the ocular relevant hydrophobic drug, cyclosporine A (CsA), a non-irritant ocular penetration enhancer is showcased, which may be used for the formulation of hydrophobic actives. The activity of this penetration enhancer is demonstrated in a healthy rabbit model. The Molecular Envelope Technology (MET) polymer (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan), a self-assembling, micelle-forming polymer, was used to formulate CsA into sterile filtered nanoparticulate eye drop formulations and the stability of the formulation tested. Healthy rabbits were dosed with a single dose of a MET–CsA (NM133) 0.05% formulation and ocular tissues analyzed. Optically clear NM133 formulations were prepared containing between 0.01–0.1% w/v CsA and 0.375–0.75% w/v MET polymer. NM133 0.01%, NM133 0.02% and NM133 0.05% were stable for 28 days when stored at refrigeration temperature (5–6 °C) and room temperature (16–23 °C), but there was evidence of evaporation of the formulation at 40 °C. There was no change in drug content when NM133 0.05% was stored for 387 days at 4 °C. On topical dosing to rabbits, corneal, conjunctival and scleral AUC0–24 levels were 25,780 ng.h g−1, 12,046 ng.h g−1 and 5879 ng.h g−1, respectively, with NM133 0.05%. Meanwhile, a similar dose of Restasis 0.05% yielded lower values of 4726 ng.h/g, 4813 ng.h/g and 1729 ng.h/g for the drug corneal, conjunctival and scleral levels, respectively. NM133 thus delivered up to five times more CsA to the ocular surface tissues when compared to Restasis. The MET polymer was non-irritant up to a concentration of 4% w/v. The MET polymer is a non-irritant ocular penetration enhancer that may be used to deliver hydrophobic drugs in optically clear topical ocular formulations.

A Review on Polymeric Nano Micelles Based Delivery to the Posterior Segment of the Eye

2020 ◽  
Vol 10 (5) ◽  
pp. 591-601
Author(s):  
Sheetal Devi ◽  
Shailendra Bhatt ◽  
Vipin Saini ◽  
Manish Kumar ◽  
Aman Deep
Keyword(s):  
Polymeric Micelles ◽  
Drug Loading ◽  
Solvent Evaporation ◽  
Ocular Tissues ◽  
Water Emulsion ◽  
Oil In Water ◽  
Dialysis Method ◽  
Prolonged Retention ◽  
Tear Turnover ◽  
Oil In Water Emulsion

Introduction: Many nanoformulations have been designed and evaluated for ocular drug delivery system consistently. These nanoformulations are designed for prolonged retention and course time, stable, efficient and reversible drug loading. The ocular bioavailability is very less when the drug is given through topically. Various anatomical and physiological limitations, for example, tear turnover, nasal lachrymal waste, reflex squinting, and visual static and dynamic hindrances cause the challenges and delay the ocular drug permeation because of the limitation that less than 5% dose can reach into the ocular tissues. Different types of Polymeric micelles were prepared to overcome the above challenges. Polymeric nano micelles are prepared by different methods, such as direct dissolution, dialysis method, Oil-in-water emulsion, solvent evaporation, co-solvent evaporation, and freeze-drying method.

The Role of Hydrophobicity in the Stability and pH-Switchability of (RXDX)4 and Coumarin-RXDX Conjugate β-Sheets

2020 ◽  
Author(s):  
Ryan Weber ◽  
Martin McCullagh
Keyword(s):  
Biological Imaging ◽  
Ph Sensing ◽  
Hydrophobic Residue ◽  
Ideal Candidate ◽  
Self Assembling ◽  
Sensing Applications ◽  
Β Sheets ◽  
The Stability ◽  
Dynamics Simulations

<p>pH-switchable, self-assembling materials are of interest in biological imaging and sensing applications. Here we propose that combining the pH-switchability of RXDX (X=Ala, Val, Leu, Ile, Phe) peptides and the optical properties of coumarin creates an ideal candidate for these materials. This suggestion is tested with a thorough set of all-atom molecular dynamics simulations. We first investigate the dependence of pH-switchabiliy on the identity of the hydrophobic residue, X, in the bare (RXDX)<sub>4</sub> systems. Increasing the hydrophobicity stabilizes the fiber which, in turn, reduces the pH-switchabilty of the system. This behavior is found to be somewhat transferable to systems in which a single hydrophobic residue is replaced with a coumarin containing amino acid. In this case, conjugates with X=Ala are found to be unstable and both pHs while conjugates with X=Val, Leu, Ile and Phe are found to form stable β-sheets at least at neutral pH. The (RFDF)<sub>4</sub>-coumarin conjugate is found to have the largest relative entropy value of 0.884 +/- 0.001 between neutral and acidic coumarin ordering distributions. Thus, we posit that coumarin-(RFDF)<sub>4</sub> containing peptide sequences are ideal candidates for pH-sensing bioelectronic materials.</p>

scholarly journals Influence of Whey Protein Micro-Gel Particles and Whey Protein Micro-Gel Particles-Xanthan Gum Complexes on the Stability of O/W Emulsions

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2301
Author(s):  
Man Zhang ◽  
Bin Liang ◽  
Hongjun He ◽  
Changjian Ji ◽  
Tingting Cui ◽  
...  
Keyword(s):  
Oxidative Stability ◽  
Whey Protein ◽  
High Speed ◽  
Xanthan Gum ◽  
Physical Stability ◽  
Theoretical Support ◽  
Gel Particles ◽  
Oil In Water ◽  
The Stability ◽  
The Impact

Appropriate pretreatment of proteins and addition of xanthan gum (XG) has the potential to improve the stability of oil-in-water (O/W) emulsions. However, the factors that regulate the enhancement and the mechanism are still not clear, which restricts the realization of improving the emulsion stability by directional design of its structure. Therefore, the effects of whey protein micro-gel particles (WPMPs) and WPMPs-XG complexes on the stability of O/W emulsion were investigated in this article to provide theoretical support. WPMPs with different structures were prepared by pretreatment (controlled high-speed shear treatment of heat-set WPC gels) at pH 3.5–8.5. The impact of initial WPC structure and XG addition on Turbiscan Indexes, mean droplet size and the peroxide values of O/W emulsions was investigated. The results indicate that WPMPs and XG can respectively inhibit droplet coalescence and gravitational separation to improve the physical stability of WPC-stabilized O/W emulsions. The pretreatment significantly enhanced the oxidative stability of WPC-stabilized O/W emulsions. The addition of XG did not necessarily enhance the oxidative stability of O/W emulsions. Whether the oxidative stability of the O/W emulsion with XG is increased or decreased depends on the interface structure of the protein-XG complex. This study has significant implications for the development of novel structures containing lipid phases that are susceptible to oxidation.

scholarly journals Melt-Cast Films Significantly Enhance Triamcinolone Acetonide Delivery to the Deeper Ocular Tissues

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 158
Author(s):  
Akshaya Tatke ◽  
Narendar Dudhipala ◽  
Karthik Janga ◽  
Bhavik Soneta ◽  
Bharathi Avula ◽  
...  
Keyword(s):  
Triamcinolone Acetonide ◽  
Polymer Matrix ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Invasive Technique ◽  
Content Uniformity ◽  
Scanning Calorimetry ◽  
Ocular Tissues

Delivering an effective drug load to the posterior section of the ocular tissues, while using a non-invasive technique, has always been a challenge. In this regard, the goal of the present study was to develop sustained release triamcinolone acetonide (TA) loaded polymeric matrix films for ocular delivery. The TA-films were prepared in two different polymer matrices, with drug loadings of 10% and 20% w/w, and they were evaluated for ocular distribution in vivo in a conscious rabbit model. A 4% w/v TA suspension (TA-C) was used as a control for in vitro and in vivo studies. The TA-films, prepared with melt-cast technology, used polyethylene oxide (PEO) and Soluplus® as the polymer matrix. The films were evaluated with respect to assay, content uniformity, excipient interaction, and permeability across isolated rabbit sclera. The distribution of TA in the ocular tissues, post topical administration, was determined in New Zealand male albino rabbits as a function of dose, and was compared against TA-C. The assay of the 10% and 20% w/w film was in the range from 70–79% and 92–94% for the Soluplus® and PEO films, respectively, and content uniformity was in the range of 95–103% for both the films. The assay of the TA from Soluplus® films was less compared with the PEO films and showed an interaction with TA, as revealed by Differential Scanning Calorimetry (DSC). Hence, Soluplus® films were not selected for further studies. No interaction was observed between the drug and PEO polymer matrix. The enhancement of trans-scleral flux and permeability of TA was about 1.16 and 1.33-folds, respectively, from the 10% w/w PEO and 3.5 and 2.12-folds, respectively, from the 20% w/w PEO films, as compared with TA-C formulations. The in vivo studies demonstrate that significantly higher TA levels were observed in the anterior and posterior segments of the eye at the end of 6h with the PEO films. Therefore, the PEO based polymeric films were able to deliver TA into the back of the eye efficiently and for prolonged periods.

scholarly journals Assessment of Fennel Oil Microfluidized Nanoemulsions Stabilization by Advanced Performance Xanthan Gum

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 693
Author(s):  
Rubén Llinares ◽  
Pablo Ramírez ◽  
José Antonio Carmona ◽  
Luis Alfonso Trujillo-Cayado ◽  
José Muñoz
Keyword(s):  
Essential Oil ◽  
Rheological Properties ◽  
Xanthan Gum ◽  
Mechanical Energy ◽  
Physical Stability ◽  
Processing Condition ◽  
Oil In Water ◽  
Mechanical Spectra ◽  
The Stability ◽  
Fennel Oil

In this work, nanoemulsion-based delivery system was developed by encapsulation of fennel essential oil. A response surface methodology was used to study the influence of the processing conditions in order to obtain monomodal nanoemulsions of fennel essential oil using the microchannel homogenization technique. Results showed that it was possible to obtain nanoemulsions with very narrow monomodal distributions that were homogeneous over the whole observation period (three months) when the appropriate mechanical energy was supplied by microfluidization at 14 MPa and 12 passes. Once the optimal processing condition was established, nanoemulsions were formulated with advanced performance xanthan gum, which was used as both viscosity modifier and emulsion stabilizer. As a result, more desirable results with enhanced physical stability and rheological properties were obtained. From the study of mechanical spectra as a function of aging time, the stability of the nanoemulsions weak gels was confirmed. The mechanical spectra as a function of hydrocolloid concentration revealed that the rheological properties are marked by the biopolymer network and could be modulated depending on the amount of added gum. Therefore, this research supports the role of advanced performance xanthan gum as a stabilizer of microfluidized fennel oil-in-water nanoemulsions. In addition, the results of this research could be useful to design and formulate functional oil-in-water nanoemulsions with potential application in the food industry for the delivery of nutraceuticals and antimicrobials.

Development of Curcumin-Loaded Polymeric Mixed Micelle for Skin Moisturizing Antioxidant Formulation

2021 ◽  
Vol 901 ◽  
pp. 98-103
Author(s):  
Sunee Channarong ◽  
Parapat Sobharaksha ◽  
Chanchai Sardseangjun ◽  
Panipak Vasvid
Keyword(s):  
Mixed Micelle ◽  
Polymeric Micelles ◽  
Entrapment Efficiency ◽  
Water Soluble ◽  
Poloxamer 407 ◽  
Average Particle ◽  
Yellow Color ◽  
Stability Data ◽  
Hydrogenated Castor Oil ◽  
The Stability

Abstract The aim of this study was to fabricate curcumin-loaded polymeric mixed micelle which was a new nanocarrier of therpeutic agent for skin uses. Curcumin was extracted from dried turmeric rhizomes using ethanol and recrystallized. The purity of curcumin was 79±3.6 %w/w. Six curcumin-loaded polymeric micelles (PM1-PM6) were prepared by simple dissolution method using poloxamer 407 (5% and 10%) as a main core structure. PEG-40 hydrogenated castor oil (PEG-40HCO) was incorporated at two percentages (2.5% and 5.0%) to study the effect on the nanoparticle characteristics. The average particle sizes of PM1-PM6 were in the range of 33.3±6.6 nm to 171.3±52.8 nm. The entrapment efficiency and the loading capacity of curcumin were in the range of 47.45%-77.35% and 0.048%w/w-0.078%w/w, respectively. When PEG-40HCO was incorporated in to the polymeric micelles, the particle size decreased and the entrapment efficiency increased. Thus, PM4 and PM5 were selected for further study. Moisturizing antioxidant creams containing 0.005%w/w of curcumin loaded in PM4, PM5 and curcumin simply dissolved in propylene glycol (PG) were formulated. The resulted formulations showed good spreadability and good characteristics. After being subjected to accelerated test, all of the formulations remained with characteristic color, pH and showed no phase separation. The stability data showed that the moisturizing antioxidant creams were stable for the whole 3 months after storage at accelerated temperature (45°C/75%RH). The study demonstrated that polymeric mixed micelle spontaneously encapsulated a poorly water-soluble curcumin and increased the solubility up to 250 folds. The developed moisturizing cream containing 0.005%w/w of curcumin resulted a greenish-yellow color preparation. It had tolerable physicochemical properties based on curcumin content, pH and viscosity under the harsh condition. The cream also had satisfactory antioxidant activity, which can be regarded as an effective and acceptable therapeutic or skincare products for topical uses.

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.

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