scholarly journals Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 986
Author(s):  
Francisco J. Cimas ◽  
Enrique Niza ◽  
Alberto Juan ◽  
María del Mar Noblejas-López ◽  
Iván Bravo ◽  
...  
Keyword(s):  
Polymeric Nanoparticles ◽  
Controlled Delivery ◽  
New Family ◽  
Bet Inhibitors ◽  
Release Studies ◽  
Bromodomain Proteins ◽  
Therapeutic Properties ◽  
Tumoral Cells ◽  
Efficacy Profile

Bromo and extraterminal domain (BET) inhibitors-PROteolysis TArgeting Chimera (BETi-PROTAC) is a new family of compounds that induce proteasomal degradation through the ubiquitination of the tagged to BET inhibitors Bromodomain proteins, BRD2 and BRD. The encapsulation and controlled release of BET-PROTACs through their vectorization with antibodies, like trastuzumab, could facilitate their pharmacokinetic and efficacy profile. Antibody conjugated nanoparticles (ACNPs) using PROTACs have not been designed and evaluated. In this pioneer approach, the commercial MZ1 PROTAC was encapsulated into the FDA-approved polymeric nanoparticles. The nanoparticles were conjugated with trastuzumab to guide the delivery of MZ1 to breast tumoral cells that overexpress HER2. These ACNPs were characterized by means of size, polydispersity index, and Z-potential. Morphology of the nanoparticles, along with stability and release studies, completed the characterization. MZ1-loaded ACNPs showed a significant cytotoxic effect maintaining its mechanism of action and improving its therapeutic properties.

scholarly journals Fabrication and In Vitro Evaluation of pH-Sensitive Polymeric Hydrogels as Controlled Release Carriers

Gels ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 110
Author(s):  
Muhammad Suhail ◽  
Chih-Wun Fang ◽  
Arshad Khan ◽  
Muhammad Usman Minhas ◽  
Pao-Chu Wu
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Acrylic Acid ◽  
Chondroitin Sulfate ◽  
Diclofenac Sodium ◽  
Research Work ◽  
Controlled Delivery ◽  
Scanning Calorimetry ◽  
Release Studies

The purpose of the current investigation was to develop chondroitin sulfate/carbopol-co-poly(acrylic acid) (CS/CBP-co-PAA) hydrogels for controlled delivery of diclofenac sodium (DS). Different concentrations of polymers chondroitin sulfate (CS), carbopol 934 (CBP), and monomer acrylic acid (AA) were cross-linked by ethylene glycol dimethylacrylate (EGDMA) in the presence of ammonium peroxodisulfate (APS) (initiator). The fabricated hydrogels were characterized for further experiments. Characterizations such as Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), and Fourier transform infrared spectroscopy (FTIR) were conducted to understand the surface morphology, thermodynamic stability, crystallinity of the drug, ingredients, and developed hydrogels. The swelling and drug release studies were conducted at two different pH mediums (pH 1.2 and 7.4), and pH-dependent swelling and drug release was shown due to the presence of functional groups of both polymers and monomers; hence, greater swelling and drug release was observed at the higher pH (pH 7.4). The percent drug release of the developed system and commercially available product cataflam was compared and high controlled release of the drug from the developed system was observed at both low and high pH. The mechanism of drug release from the hydrogels followed Korsmeyer–Peppas model. Conclusively, the current research work demonstrated that the prepared hydrogel could be considered as a suitable candidate for controlled delivery of diclofenac sodium.

scholarly journals Efficient Clearance of Aspergillus fumigatus in Murine Lungs by an Ultrashort Antimicrobial Lipopeptide, Palmitoyl-Lys-Ala-dAla-Lys

2008 ◽  
Vol 52 (9) ◽  
pp. 3118-3126 ◽  
Author(s):  
Alexandra Vallon-Eberhard ◽  
Arik Makovitzki ◽  
Anne Beauvais ◽  
Jean-Paul Latgé ◽  
Steffen Jung ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Microscopic Analysis ◽  
Current Standard ◽  
New Family ◽  
Therapeutic Properties ◽  
Survival Assay ◽  
Opportunistic Fungal Pathogen

ABSTRACT Aspergillus fumigatus is an opportunistic fungal pathogen responsible for invasive aspergillosis in immunocompromised individuals. The inefficiency of antifungal agents and high mortality rate resulting from invasive aspergillosis remain major clinical concerns. Recently, we reported on a new family of ultrashort cationic lipopeptides active in vitro against fungi. Mode of action studies supported a membranolytic or a detergent-like effect. Here, we screened several lipopeptides in vitro for their anti-A. fumigatus activity. To investigate the therapeutic properties of the selected peptides in vivo, we challenged immunosuppressed C57BL/6 wild-type mice intranasally with DsRed-labeled A. fumigatus conidia and subsequently treated the animals locally with the lipopeptides. Confocal microscopic analysis revealed the degradation of DsRed-labeled hyphal forms and residual conidia in the lungs of the mice. The most efficient peptide was tested further using a survival assay and was found to significantly prolong the life of the treated animals, whereas no mice survived with the current standard antifungal treatment with amphotericin B. Moreover, as opposed to the drug-treated lungs, the peptide-treated lungs did not display any toxicity of the peptide. Our results highlight the potential of this family of lipopeptides for the treatment of pulmonary invasive aspergillosis.

pH Responsive Polymeric Nanoparticles for Oral Insulin Delivery

2017 ◽  
pp. 6-10
Author(s):  
Charu Tyagi
Keyword(s):  
Insulin Release ◽  
Polymeric Nanoparticles ◽  
Attenuated Total Reflectance ◽  
Ph Responsive ◽  
Eudragit L100 ◽  
Release Studies ◽  
Mean Size ◽  
The Mean ◽  
In Vitro Insulin Release

Gelatin-eudragit L100 nanoparticles of wet size range 170-563nm were prepared by two step dissolvation method and the effect of different concentrations of eudragit L100 and emulsifying agent - sodium lauryl sulphate (SLS) - on the particle size were studied. Synthesized nanoparticles were characterized by attenuated total reflectance-fourier transform infrared spectroscopy (ATRFTIR) and the mean size distribution. Insulin loading was done at a pH 7.4 and the in vitro insulin release studies of nanoparticles were carried out by simulating gastrointestinal tract condition which showed the minimal insulin release at pH 2.5 (20% in 90min) while appreciable release (40% in first 30min) at pH of 7.4. This pH responsive release pattern of the synthesized nanoparticles confers on the insulin protection from proteolytic degradation in acidic environment of stomach and upper intestinal part while enhancing bioavailability in the later part of intestine.

Preparation, characterization and in vitro drug release studies of novel polymeric nanoparticles

2006 ◽  
Vol 323 (1-2) ◽  
pp. 146-152 ◽  
Author(s):  
Surendra Nimesh ◽  
Romila Manchanda ◽  
Rupesh Kumar ◽  
Amit Saxena ◽  
Preeti Chaudhary ◽  
...  
Keyword(s):  
Drug Release ◽  
Polymeric Nanoparticles ◽  
In Vitro Drug Release ◽  
Release Studies

scholarly journals Formulation and Evaluation of Pseudoephedrine Hydrochloride Loaded Alginate Microbeads

2020 ◽  
Vol 10 (3) ◽  
pp. 137-141
Author(s):  
Rashmi Dahima
Keyword(s):  
Drug Release ◽  
Sodium Alginate ◽  
Cost Effective ◽  
Alginate Beads ◽  
Controlled Delivery ◽  
In Vitro Drug Release ◽  
Release Studies ◽  
Multiple Unit ◽  
Effective Carrier

Multiple unit dosage forms such as microbeads have increased acceptance because of added even spreading of the drug in the gastrointestinal tract, unvarying drug absorption, abridged local irritation and removal of undesirable intestinal retaining of polymeric material, when compared to non-disintegrating single unit dosage form. The purpose of the presented research is to develop microbeads of pseudoephedrine hydrochloride utilizing sodium alginate as the hydrophilic carrier in combination with HPMC as drug release modifier to lessen the dosing frequency and thereby advance the patient compliance. The microbeads were formulated by varying concentrations of HPMC and calcium chloride. The optimum formulation was chosen based upon in vitro drug release studies and further evaluated. The compatibility of drug-polymer was studied using FTIR analysis. The prepared formulation underwent evaluation for various parameters like drug entrapment, microbeads size, swelling index, mucoadhesive property and stability. No significant drug-polymer interactions were observed in compatibility studies and the formulation was found to be stable on 45 days storage. The formulations exhibited an extended drug release pattern which was the ultimate aim of the study. The microbeads represented good yield, high drug entrapment, low microbeads size and appropriate swelling property. The in vitro wash-off test indicated that the sodium alginate microbeads represent decent mucoadhesive properties. Henceforth, the formulated HPMC coated sodium alginate beads can be utilized as a substitute and cost-effective carrier for the oral controlled delivery of pseudoephedrine hydrochloride. Keywords: microbeads, pseudoephedrine hydrochloride, sodium alginate, drug release

Development and Evaluation of a Novel Topical Treatment for Acne with Azelaic Acid-Loaded Nanoparticles

2013 ◽  
Vol 19 (5) ◽  
pp. 1141-1150 ◽  
Author(s):  
Catarina Pinto Reis ◽  
Ana Gomes ◽  
Patrícia Rijo ◽  
Sara Candeias ◽  
Pedro Pinto ◽  
...  
Keyword(s):  
Drug Release ◽  
Azelaic Acid ◽  
Topical Treatment ◽  
Polymeric Nanoparticles ◽  
Differential Scanning Calorimetric ◽  
Calorimetric Analysis ◽  
Control Drug ◽  
Release Studies ◽  
Mean Size

AbstractAzelaic acid (AzA) is used in the treatment of acne. However, side effects and low compliance have been associated with several topical treatments with AzA. Nanotechnology presents a strategy that can overcome these problems. Polymeric nanoparticles can control drug release and targeting and reduce local drug toxicity. The aim of this study was to produce and evaluate an innovative topical treatment for acne with AzA-loaded poly-dl-lactide/glycolide copolymer nanoparticles. A soft white powder of nanoparticles was prepared. The mean size of loaded nanoparticles was <400 nm and zeta potential was negative. Spherical nanoparticles were observed by scanning electron microscopy. Encapsulation efficiency was around 80% and a strong interaction between the polymer and the drug was confirmed by differential scanning calorimetric analysis. In vitro drug release studies suggested a controlled and pulsatile release profile. System efficacy tests suggested similar results between the loaded nanoparticles and the nonencapsulated drug against the most common bacteria associated with acne. Cytotoxicity of AzA-loaded nanoparticles was concentration dependent, although not pronounced. The occluded patch test seemed to indicate that the formulation excipients were safe and thus AzA-loaded nanoparticles appear to be an efficient and safe treatment for acne.

scholarly journals In-vitro Investigation of Polymeric Lipid Hybrid Nanoparticles (Plhns) Of a Chemotherapeutic Drug for the Treatment of Glioblastoma Multiforme

2021 ◽  
Author(s):  
Sankha Bhattacharya
Keyword(s):  
Particle Size ◽  
Polymeric Nanoparticles ◽  
Tween 80 ◽  
Homogenization Method ◽  
Hybrid Nanoparticles ◽  
In Vitro Drug Release ◽  
Anticancer Effects ◽  
Release Studies ◽  
In Vitro Investigation

PHLNs (polymeric lipid hybrid nanoparticles) are core&ndash;shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) &amp; glyceryl tripalmitate prepared using solvent injection &amp; homogenization method for glioblastoma treatment option. The MTX loaded PLHNPs optimized by Box&ndash;Behnken design to minimize particle size, higher entrapment efficacy, and maximize MTX concentration in the brain at 4h. The particle size, entrapment efficacy, concentration of drug in brain at 4h, zeta potential and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51-233.37nm, 70.56-86.34%, 6.38-12.38 &mu;g/mL, 25.78-36.31mV &amp; 1.02-5.32. in-vitro drug release studies, cellular internalization of optimized formulation against U-87 MG shows good anticancer effects.

scholarly journals BET bromodomain inhibitor HMBA synergizes with MEK inhibition in treatment of malignant glioma

2020 ◽  
Author(s):  
Elisa Funck-Brentano ◽  
Dzeneta Vizlin-Hodzic ◽  
Jonas A. Nilsson ◽  
Lisa M. Nilsson
Keyword(s):  
Biological Activities ◽  
Glioma Cells ◽  
Resistance Mechanisms ◽  
Transcriptional Elongation ◽  
Mek Inhibitors ◽  
Bet Inhibitors ◽  
Bromodomain Proteins ◽  
Cancer Multiple

Abstract(1)BackgroundBET bromodomain proteins regulate transcription by binding acetylated histones and attracting key factors for e.g. transcriptional elongation. BET inhibitors have been developed to block pathogenic processes such as cancer and inflammation. Despite having potent biological activities, BET inhibitors have still not made a breakthrough in clinical use for treating cancer. Multiple resistance mechanisms have been proposed but thus far no attempts to block this in glioma has been made.(2)MethodsHere, we have conducted a pharmacological synergy screen in glioma cells to search for possible combination treatments augmenting the apoptotic response to BET inhibitors. We first used HMBA, a compound that was developed as a differentiation therapy four decades ago but more recently was shown to primarily inhibit BET bromodomain proteins. Data was also generated using other BET inhibitors.(3)ResultsIn the synergy screen, we discovered that several MEK inhibitors can enhance apoptosis in response to HMBA in rat and human glioma cells in vitro as well as in vivo xenografts. The combination is not unique to HMBA but also other BET inhibitors such as JQ1 and I-BET-762 can synergize with MEK inhibitors.(4)ConclusionsOur findings validate a combination therapy previously demonstrated to exhibit anti-cancer activities in multiple other tumor types but which appears to have been lost in translation to the clinic.

Synthesis, Characterization and in-vitro drug release studies of a macromolecular prodrug of Didanosine.

2010 ◽  
Vol 2 (2) ◽  
Author(s):  
Neeraj Agrawal ◽  
M.J. Chandrasekar ◽  
U.V. Sara ◽  
Rohini A.
Keyword(s):  
Drug Release ◽  
Drug Level ◽  
Drug Release Profile ◽  
Sustained Drug Release ◽  
In Vitro Drug Release ◽  
Alkaline Environment ◽  
Stomach Acid ◽  
Release Studies ◽  
Macromolecular Prodrug

A macromolecular prodrug of didanosine (ddI) for oral administration was synthesized and evaluated for in-vitro drug release profile. Didanosine was first coupled to 2-hydroxy ethyl methacrylate (HEMA) through a succinic spacer to form HEMA-Suc-ddI monomeric conjugate which was subsequently polymerized to yield Poly(HEMA-Suc-ddI) conjugate. The structures of the synthesized compounds were characterized by FT-IR, Mass and 1H-NMR spectroscopy. The prodrug was subjected for in-vitro drug release studies in buffers of pH 1.2 and 7.4 mimicking the upper and lower GIT. The results showed that the drug release from the polymeric backbone takes place in a sustained manner over a period of 24 h and the amount of drug released was comparatively higher at pH 7.4 indicating that the drug release takes place predominantly at the alkaline environment of the lower GIT rather than at the acidic environment of the upper GIT. This pH dependent sustained drug release behavior of the prodrug may be capable of reducing the dose limiting toxicities by maintaining the plasma drug level within the therapeutic range and increasing t1/2 of ddI. Moreover, the bioavailability of the drug should be improved as the prodrug releases ddI predominantly in the alkaline environment which will reduce the degradation of ddI in the stomach acid.

Preparation and in vitro Evaluation of Bioadhesive Microparticulate System

1970 ◽  
Vol 1 (3) ◽  
pp. 257-266
Author(s):  
Nagda C. D. ◽  
Chotai N. P. ◽  
Patel S. B. ◽  
Soni T. J ◽  
Patel U. L
Keyword(s):  
Drug Loading ◽  
In Vitro Release ◽  
Phenyl Acetic Acid ◽  
Solvent Evaporation Method ◽  
Elimination Half ◽  
Release Studies ◽  
Differential Scanning Colorimetry ◽  
Polymer Interactions ◽  
Vitro Release

Aceclofenac (ACE) is NSAIDs of a phenyl acetic acid class. It is indicated in arthritis and osteoarthritis, rheumatoid arthritis, ankylosing spondylitis. It has short elimination half life of 4 hours. The objective of the study is to design, characterize and evaluate bioadhesive microspheres of ACE employing carbopol (CP) as bioadhesive polymer. Bioadhesive microspheres of ACE were prepared by solvent evaporation method. The prepared microspheres were free flowing and spherical in shape and characterized for drug loading, mucoadhesion test, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in-vitro release studies were performed using pH 6.8 phosphate buffer. The drug loaded microspheres in a ratio of 1:5 showed 47% of drug entrapment; percentage mucoadhesion was 81% and 89% release in 10 h. The infrared spectra and DSC showed stable character of aceclofenac in the drug loaded microspheres and revealed the absence of drug-polymer interactions. SEM studies showed that the microspheres are spherical and porous in nature. The in vitro release profiles from microspheres of different polymer-drug ratios followed Higuchi model.

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