scholarly journals A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 795
Author(s):  
Laura Nižić Nodilo ◽  
Ivo Ugrina ◽  
Drago Špoljarić ◽  
Daniela Amidžić Klarić ◽  
Cvijeta Jakobušić Brala ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Brain Targeting ◽  
Formulation Development ◽  
Flow Properties ◽  
In Vitro Biocompatibility ◽  
Dose Fraction ◽  
Delivery Platform ◽  
3D Printed ◽  
Quality By Design Approach

Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.

3D Printed PLA/PCL/TiO2 Composite for Bone Replacement and Grafting

MRS Advances ◽  
2018 ◽  
Vol 3 (40) ◽  
pp. 2373-2378 ◽  
Author(s):  
Sandra E. Nájera ◽  
Monica Michel ◽  
Nam-Soo Kim
Keyword(s):  
Biomedical Applications ◽  
Fused Deposition Modeling ◽  
Fracture Strain ◽  
Fused Deposition ◽  
In Vitro Biocompatibility ◽  
Bone Replacement ◽  
Deposition Modeling ◽  
3D Printed ◽  
The Stability

ABSTRACTPolymer composites of Polylactic acid (PLA) and poly-ε-caprolactone (PCL), containing small amounts of titanium oxide (TiO2) were developed for biomedical applications. These composite materials were prepared, and then printed using Fused Deposition Modeling (FDM). 3D printed structures were characterized to determine their mechanical properties and biocompatibility. DSC analysis yielded useful information regarding the immiscibility of the different polymers, and it was observed that the particles of TiO2 improved the stability of the polymers. The ultimate tensile strength and the fracture strain increased by adding TiO2 as a filler, resulting in values of approximately 45 MPa and 5.5 % elongation. The printed composites show excellent in vitro biocompatibility including cell proliferation and adhesion, and are therefore promising candidates to be used in the biomedical field for bone replacement procedures, due to their properties similar to those of cancellous bone.

scholarly journals Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease

Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yun Tan ◽  
Yao Liu ◽  
Yujing Liu ◽  
Rui Ma ◽  
Jingshan Luo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Nasal Cavity ◽  
Dopaminergic Neurons ◽  
Rational Design ◽  
Brain Targeting ◽  
Solution Temperature ◽  
Delivery Platform

Mitochondrial dysfunction is commonly detected in individuals suffering from Parkinson’s disease (PD), presenting within the form of excessive reactive oxygen species (ROS) generation as well as energy metabolism. Overcoming this dysfunction within brain tissues is an effective approach to treat PD, while unluckily, the blood-brain barrier (BBB) substantially impedes intracerebral drug delivery. In an effort to improve the delivery of efficacious therapeutic drugs to the brain, a drug delivery platform hydrogel (MAG-NCs@Gel) was designed by complexing magnolol (MAG)-nanocrystals (MAG-NCs) into the noninvasive thermosensitive poly(N-isopropylacrylamide) (PNIPAM) with self-gelation. The as-prepared MAG-NCs@Gel exhibited obvious improvements in drug solubility, the duration of residence with the nasal cavity, and the efficiency of brain targeting, respectively. Above all, continuous intranasal MAG-NCs@Gel delivery enabled MAG to cross the BBB and enter dopaminergic neurons, thereby effectively alleviating the symptoms of MPTP-induced PD. Taking advantage of the lower critical solution temperature (LCST) behavior of this delivery platform increases its viscoelasticity in nasal cavity, thus improving the efficiency of MAG-NCs transit across the BBB. As such, MAG-NCs@Gel represented an effective delivery platform capable of normalizing ROS and adenosine triphosphate (ATP) in the mitochondria of dopaminergic neurons, consequently reversing the mitochondrial dysfunction and enhancing the behavioral skills of PD mice without adversely affecting normal tissues.

Formulation Development and Characterization of Darunavir and Ritonavir Sustained Release Tablets using Quality by Design Approach

2021 ◽  
Vol 23 (08) ◽  
pp. 906-930
Author(s):  
Dhaval Patel ◽  
◽  
Hitesh Patel ◽  
Hiren Chaudhary ◽  
◽  
...  
Keyword(s):  
Quality By Design ◽  
Plasma Concentrations ◽  
Matrix Tablets ◽  
Tween 20 ◽  
Cytochrome P450 3A ◽  
Formulation Development ◽  
Sodium Phosphate Buffer ◽  
Sustained Release Tablets ◽  
Quality By Design Approach

Darunavir is a nonpeptidic inhibitor of protease and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes. It is usually coadministered with low-dose ritonavir (Darunavir/r). Ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances Darunavir which leads to increased plasma concentrations of darunavir and allows for daily lower dose. Here, we have developed combination SR formulation of Darunavir and Ritonavir and evaluated. In vitro drug release of all formulations was carried out in dissolution medium 900ml of pH 3.0, 0.05 M Sodium Phosphate Buffer + 2% Tween 20 for 75 RPM USP II apparatus (paddle). The results shown that, all the formulations of matrix tablets shown the good release of drug from trialed formulations however all formulations were not releasing the drug in enough amount. In matrix tablets F6, the release of drug shows NLT 80%. So, the formulation F6 have been considered as suitable for the SR tablet of Darunavir and Ritonavir. Tablets were also evaluated though Quality by Design (QbD) method.

scholarly journals Real-Time Live-Cell Imaging Technology Enables High-Throughput Screening to Verify in Vitro Biocompatibility of 3D Printed Materials

Materials ◽  
2019 ◽  
Vol 12 (13) ◽  
pp. 2125 ◽  
Author(s):  
Ina G. Siller ◽  
Anton Enders ◽  
Tobias Steinwedel ◽  
Niklas-Maximilian Epping ◽  
Marline Kirsch ◽  
...  
Keyword(s):  
3D Printing ◽  
High Throughput Screening ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
Post Processing ◽  
In Vitro Biocompatibility ◽  
3D Printed ◽  
Printed Materials

With growing advances in three-dimensional (3D) printing technology, the availability and diversity of printing materials has rapidly increased over the last years. 3D printing has quickly become a useful tool for biomedical and various laboratory applications, offering a tremendous potential for efficiently fabricating complex devices in a short period of time. However, there still remains a lack of information regarding the impact of printing materials and post-processing techniques on cell behavior. This study introduces real-time live-cell imaging technology as a fast, user-friendly, and high-throughput screening strategy to verify the in vitro biocompatibility of 3D printed materials. Polyacrylate-based photopolymer material was printed using high-resolution 3D printing techniques, post-processed using three different procedures, and then analyzed with respect to its effects on cell viability, apoptosis, and necrosis of adipogenic mesenchymal stem cells (MSCs). When using ethanol for the post-processing procedure and disinfection, no significant effects on MSCs could be detected. For the analyses a novel image-based live-cell analysis system was compared against a biochemical-based standard plate reader assay and traditional flow cytometry. This comparison illustrates the superiority of using image-based detection of in vitro biocompatibility with respect to analysis time, usability, and scientific outcome.

scholarly journals Formulation development and characterization of in-situ gel of Rizatriptan Benzoate for intranasal delivery

2021 ◽  
Vol 11 (1-s) ◽  
pp. 1-6
Author(s):  
Jalaram H Thakkar ◽  
Shailesh T. Prajapati
Keyword(s):  
Ex Vivo ◽  
Gellan Gum ◽  
Brain Targeting ◽  
Great Promise ◽  
Formulation Development ◽  
In Situ Gel ◽  
Rizatriptan Benzoate ◽  
32 Factorial Design

The present investigation was aimed to formulate and characterize ion-activated in-situ gel loaded with Rizatriptan Benzoate (RIZ) for intranasal administration for brain targeting. The gel was further optimized for process and formulation parameters by using 32 factorial design. The optimized batch having the concentrations of gellan gum and HPMC E15 LV 33.83 mg and 9.6 mg respectively. Gel strength and mucoadhesive strength of the optimized formulation were found to be 32.54 sec and 2580.50 dynes/cm2 respectively. Moreover, improved in-vitro and ex-vivo release profile of in-situ gel were observed in comparison to drug solution. In a nutshell, the developed formulation holds a great promise in overcoming the limitation associated with currently marketed RIZ formulations and illustrates the potential use of ion-activated in-situ gel to administer the drug by nasal route for brain targeting. Keywords: In-situ gel, Rizatriptan benzoate, Ion-activated, Gellan gum, HPMC E15 LV, Brain delivery, Migraine

scholarly journals Formulation Development and Characterization of Darunavir and Ritonavir Sustained Release Tablets Using Quality by Design Approach

2021 ◽  
pp. 159-172
Author(s):  
Dhaval Patel ◽  
Hitesh Patel ◽  
Hiren Chaudhary
Keyword(s):  
Quality By Design ◽  
Plasma Concentrations ◽  
Matrix Tablets ◽  
Tween 20 ◽  
Cytochrome P450 3A ◽  
Formulation Development ◽  
Sodium Phosphate Buffer ◽  
Sustained Release Tablets ◽  
Quality By Design Approach

Darunavir is a nonpeptidic inhibitor of protease and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes. It is usually coadministered with low-dose ritonavir (Darunavir/r). Ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances Darunavir which leads to increased plasma concentrations of darunavir and allows for daily lower dose. Here, we have developed combination SR formulation of Darunavir and Ritonavir and evaluated. In vitro drug release of all formulations was carried out in dissolution medium 900ml of pH 3.0, 0.05 M Sodium Phosphate Buffer + 2% Tween 20 for 75 RPM USP II apparatus (paddle). The results shown that, all the formulations of matrix tablets shown the good release of drug from trialed formulations however all formulations were not releasing the drug in enough amount. In matrix tablets F6, the release of drug shows NLT 80%. So, the formulation F6 have been considered as suitable for the SR tablet of Darunavir and Ritonavir. Tablets were also evaluated though Quality by Design (QbD) method.

scholarly journals Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 831
Author(s):  
Tatyana Kovshova ◽  
Nadezhda Osipova ◽  
Anna Alekseeva ◽  
Julia Malinovskaya ◽  
Alexey Belov ◽  
...  
Keyword(s):  
Drug Release ◽  
Targeted Delivery ◽  
Compartmental Analysis ◽  
Formulation Development ◽  
Surface Design ◽  
Significant Difference ◽  
Quality By Design Approach ◽  
The One

Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro and in vivo. The nanoparticles utilize a specific surface design to modulate the lipid corona by attracting blood-borne apolipoproteins involved in the endogenous transport of chylomicrons across the blood–brain barrier. When applying this strategy, the fine balance between drug release and carrier accumulation is responsible for targeted delivery. Drug release experiments in an aqueous medium resulted in a difference in drug release of approximately 20%, while a 10% difference was found in human serum. This difference affected the partitioning of doxorubicin in human blood and was reflected by the outcome of the pharmacokinetic study in rats. For the fast-releasing formulation NanoCore-6.4, the AUC0→1h was significantly lower (2999.1 ng × h/mL) than the one of NanoCore-7.4 (3589.5 ng × h/mL). A compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model indicated a significant difference in the release behavior and targeting capability. A fraction of approximately 7.310–7.615% of NanoCore-7.4 was available for drug targeting, while for NanoCore-6.4 only 5.740–6.057% of the injected doxorubicin was accumulated. Although the targeting capabilities indicate bioequivalent behavior, they provide evidence for the quality-by-design approach followed in formulation development.

scholarly journals Xeno-Free In Vitro Cultivation and Osteogenic Differentiation of hAD-MSCs on Resorbable 3D Printed RESOMER®

Materials ◽  
2020 ◽  
Vol 13 (15) ◽  
pp. 3399
Author(s):  
Marline Kirsch ◽  
Annabelle-Christin Herder ◽  
Cécile Boudot ◽  
Andreas Karau ◽  
Jessica Rach ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Autologous Transplantation ◽  
Calf Serum ◽  
Human Mesenchymal Stem Cells ◽  
In Vitro Cultivation ◽  
Human Mscs ◽  
In Vitro Biocompatibility ◽  
Human Platelet Lysate ◽  
3D Printed

The development of alloplastic resorbable materials can revolutionize the field of implantation technology in regenerative medicine. Additional opportunities to colonize the three-dimensionally (3D) printed constructs with the patient’s own cells prior to implantation can improve the regeneration process but requires optimization of cultivation protocols. Human platelet lysate (hPL) has already proven to be a suitable replacement for fetal calf serum (FCS) in 2D and 3D cell cultures. In this study, we investigated the in vitro biocompatibility of the printed RESOMER® Filament LG D1.75 materials as well as the osteogenic differentiation of human mesenchymal stem cells (hMSCs) cultivated on 3D printed constructs under the influence of different medium supplements (FCS, human serum (HS) and hPL). Additionally, the in vitro degradation of the material was studied over six months. We demonstrated that LG D1.75 is biocompatible and has no in vitro cytotoxic effects on hMSCs. Furthermore, hMSCs grown on the constructs could be differentiated into osteoblasts, especially supported by supplementation with hPL. Over six months under physiological in vitro conditions, a distinct degradation was observed, which, however, had no influence on the biocompatibility of the material. Thus, the overall suitability of the material LG D1.75 to produce 3D printed, resorbable bone implants and the promising use of hPL in the xeno-free cultivation of human MSCs on such implants for autologous transplantation have been demonstrated.

scholarly journals Development, characterization and solubility enhancement of poorly water soluble drug telmisartan by polymer enriched bridging liquid technique using peg 4000 as hydrophilic polymer

2019 ◽  
Vol 10 (3) ◽  
pp. 2234-2241
Author(s):  
Manoj K ◽  
Seenivasan P ◽  
Arul K ◽  
Senthil kumar M
Keyword(s):  
Water Solubility ◽  
Chemical Interaction ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Hydrophilic Polymer ◽  
Formulation Development ◽  
Flow Properties ◽  
Bioavailability Enhancement ◽  
Poorly Water Soluble

The solubility and bioavailability enhancement of poorly water soluble drugs has been a foremost challenge in formulation development. Telmisartan belonging to Angiotension II receptor antagonist, extensively used candidate for the treatment of hypertension possess poor water solubility and bioavailability. Polymer Enriched Bridging Liquid (PEBL) method was adopted here for enhancing the flow properties and solubility of Telmisartan. The techniques involve the incorporation of a hydrophilic polymer, PEG4000 into the bridging liquid during the crystallisation process. The drug content determination suggested the better incorporation of polymer into the crystal aggregates. The FTIR analysis showed the absence of any chemical interaction. The DSC analysis showed a significant reduction in the enthalpy and melting point. The crystallinity of Telmisartan was reduced from 50.789 to 34.655% indicated by the reduction in peak intensity analysis and peak area calculation by X-Ray diffraction. The SEM analysis revealed the spherical nature of crystals resulting in the improvement of flow properties. The saturation solubility analysis revealed that the formulation STPG03 has shown 25.86 fold increase in the solubility in water and 24.217 folds in pH7.5 Phosphate buffer. The in vitro dissolution data also supported the results of solubility analysis. Hence PEBL technique provided a better alternative to enhance the flow characteristics, solubility, dissolution and bioavailability of Telmisartan.

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