scholarly journals P12.01 Local implantation of thermoresponsive interferon alpha-polypeptide conjugate combined with temozolomide for post-surgical glioblastoma chemoimmunotherapy

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii59-iii59
Author(s):  
P Liang ◽  
W Zhuoran ◽  
G Weiping ◽  
W Guihuai
Keyword(s):  
Release Kinetics ◽  
Physicochemical Characterization ◽  
Antitumor Agent ◽  
Genetically Engineered ◽  
Resection Cavity ◽  
Post Surgery ◽  
Zero Order Release ◽  
Immunosuppressive Microenvironment

Abstract BACKGROUND Glioblastoma(GBM) is associated with gloomy prognosis despite maximal safe resection and following chemoradiation. In recent years, significant progress has been made in cancer immunotherapy except for GBM, which is largerly due to its local immunosuppressive microenvironment. Some research has demonstrated that local immunotherapy may be more efficient than systematic administrators. IFNα has been investigated as antitumor agent for some cancers, including glioma. Nevertheless, the short circulating half-life greatly limits its clinical application. Hence, a thermoresponsive IFNα-elastin-like polypeptide (IFNα-ELP) was genetically engineered for the earliest local intervention post-surgery. MATERIAL AND METHODS Firstly, IFNα-ELP(V) was constructed, expressed and purified, then, its physicochemical characterization was verified. The tumor was resected 10 days after U87MG-mCherry-luc cells orthotopic implantation, and IFNα-ELP(V) was injected into the resection cavity. Two days later, temozolomide(TMZ) was intraperitoneally injected. Using in vivo imaging technique, we could monitor the trends in tumor size. The survival time of mice was counted. Biosafety was evaluated by peripheral blood biochemistry analysis and pathology of the organs. RESULTS In this study, the bioconjugate not only in situ deposited in the resection cavity because of the thermoresponsive characteristic, but also showed zero-order release kinetics from the depot and dramatically improved pharmacokinetics and biodistribution of IFNα. Consequently, it showed the inhibition of tumor relapse in GBM orthotopic resection mice models. When followed by TMZ intraperitoneal injection, IFNα-ELP(V) could significantly prevent the tumor recurrence than itself or TMZ alone. Biosafety results indicated that the systemic toxicity of IFNα-ELP(V) in mice can be reduced to safe levels. CONCLUSION The results reveal that local implantation of thermoresponsive IFNα-ELP(V) combined with TMZ exhibits the synergy of post-surgical GBM chemoimmunotherapy.

scholarly journals Physical Characteristics and Cell-Adhesive Properties of In Vivo Fabricated Hyaluronan/Bacterial Cellulose Nanocomposites

2021 ◽  
Author(s):  
Ryo Takahama ◽  
Honami Kato ◽  
Go Takayama ◽  
Kenji Tajima ◽  
Tetsuo Kondo
Keyword(s):  
Bacterial Cellulose ◽  
Physical Characteristics ◽  
Genetically Engineered ◽  
Basic Material ◽  
Adhesive Properties ◽  
Gluconacetobacter Hansenii ◽  
Modification Technique ◽  
Cellulose Nanocomposites

Abstract This study attempts to clarify the basic material properties of in-vivo-fabricated hyaluronan (HA)/bacterial cellulose (BC) nanocomposites prepared previously. BC membranes (pellicles) generated by Gluconacetobacter hansenii (G. hansenii) are promising biomaterials owing to their outstanding biocompatible properties. Recently, specific demands for biomedical applications of BC have increased owing to its excellent mechanical properties. Although many techniques have been developed to improve the biofunctional properties of BC pellicles, such modifications remain limited owing to technical difficulties in the modulation of complex biosynthetic processes. Therefore, we previously developed an in vivo modification technique to produce nanocomposite pellicles composed of BC and HA (in vivo HA/BC), which are directly secreted from genetically engineered G. hansenii. In the present study, the HA extractability and content rate, physical characteristics, and cytocompatibility of in vivo HA/BC have been investigated in comparison to conventional in situ HA/BC and native BC pellicle. The results suggested that HA more strongly adsorbed to the solid BC surface of in vivo HA/BC than that of in situ HA/BC, which possibly affected the dynamic viscoelastic characteristics. Furthermore, in vivo HA/BC showed remarkably high human epidermal cell adhesion. These results indicate the great potential of in vivo modification to expand the usefulness of BC-based biomaterials.

Preparation and characterization of antibacterial and anti-inflammatory hyaluronic acid-chitosan-dexamethasone hydrogels for peri-implantitis repair

2021 ◽  
pp. 088532822110479
Author(s):  
Zhen Zhou ◽  
Qiang Zhang ◽  
Yamin Wang
Keyword(s):  
Hyaluronic Acid ◽  
Physicochemical Characterization ◽  
Inflammatory Drug ◽  
Composite Hydrogels ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Nih 3T3

Numerous treatment methods for peri-implantitis have been widely used including oral cleaning, traditional metal scraping means, or local antibiotic application. However, to continuously release antibacterial and anti-inflammatory drug in location in situ for effective peri-implantitis repair is still challenging. Herein, an anti-inflammatory drug dexamethasone (DE)–incorporated hyaluronic acid (HA)-chitosan (CT) composite hydrogels system was developed to repair peri-implantitis. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogels degradation and peri-implantitis repair were assessed in mice. The results showed that the prepared multifunctional hydrogels achieved sustained release, with an equilibrium swelling of 18, and promoted the growth against NIH-3T3 fibroblast cells. The in vitro antibacterial tests showed HA-CT-DE hydrogels can inhibit methicillin-resistant Staphylococcus aureus and Escherichia coli. It down-regulated the expression levels of inflammation factor IL-1β, IL-6 and, TNF-α in peri-implantitis. The prepared HA-CT-DE composite hydrogels with integrated function is promising for the treatment of peri-implantitis.

Prolonged release of VEGF and Ang1 from intralesionally implanted hydrogel promotes perilesional vascularization and functional recovery after experimental ischemic stroke

2022 ◽  
pp. 0271678X2110699
Author(s):  
Pavel Yanev ◽  
Geralda AF van Tilborg ◽  
Annette van der Toorn ◽  
Xiangmei Kong ◽  
Ann M Stowe ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Release Kinetics ◽  
Chronic Phase ◽  
Stroke Recovery ◽  
Intralesional Injection ◽  
Prolonged Release ◽  
Post Stroke ◽  
In Situ Forming

Injectable hydrogels can generate and support pro-repair environments in injured tissue. Here we used a slow-releasing drug carrying in situ-forming hydrogel to promote post-stroke recovery in a rat model. Release kinetics were measured in vitro and in vivo with MRI, using gadolinium-labeled albumin (Galbumin), which demonstrated prolonged release over multiple weeks. Subsequently, this hydrogel was used for long-term delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) (Gel VEGF + Ang1, n = 14), in a photothrombotically induced cortical stroke lesion in rats. Control stroke animals were intralesionally injected with saline (Saline, n = 10), non-loaded gel (Gel, n = 10), or a single bolus of VEGF + Ang1 in saline (Saline VEGF + Ang1, n = 10). MRI was executed to guide hydrogel injection. Functional recovery was assessed with sensorimotor function tests, while tissue status and vascularization were monitored by serial in vivo MRI. Significant recovery from sensorimotor deficits from day 28 onwards was only measured in the Gel VEGF + Ang1 group. This was accompanied by significantly increased vascularization in the perilesional cortex. Histology confirmed (re)vascularization and neuronal sparing in perilesional areas. In conclusion, intralesional injection of in situ-forming hydrogel loaded with pro-angiogenic factors can support prolonged brain tissue regeneration and promote functional recovery in the chronic phase post-stroke.

scholarly journals Olive Oil Based Methotrexate Loaded Topical Nanoemulsion Gel for the Treatment of Imiquimod Induced Psoriasis-Like Skin Inflammation in an Animal Model

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1121
Author(s):  
Sheikh Abdur Rashid ◽  
Sajid Bashir ◽  
Faiza Naseem ◽  
Arshad Farid ◽  
Irfan A. Rather ◽  
...  
Keyword(s):  
Drug Release ◽  
Olive Oil ◽  
Release Kinetics ◽  
Skin Permeation ◽  
Physicochemical Characterization ◽  
Entrapment Efficiency ◽  
Tween 80 ◽  
Penetration Enhancers ◽  
Nanoemulsion Gel

Psoriasis, a chronic inflammatory illness, is on the rise and is linked to several other life-threatening diseases. The primary goal of this study was to create a nanoemulsion gel loaded with methotrexate and olive oil (MTX NEG). The formulation was evaluated for physicochemical characterization, entrapment efficiency, drug release kinetics, skin permeation studies and stability tests. In addition, the efficacy of MTX NEG against psoriasis was tested using imiquimod-induced psoriasis in a rat model. The final optimized MTX NEG was developed with a particle size of 202.6 ± 11.59 nm and a PDI of 0.233 ± 0.01, with a 76.57% ± 2.48% average entrapment efficiency. After 20 h, the release kinetics predicted a 72.47% drug release at pH 5.5. FTIR findings demonstrated that the optimized MTX NEG formulation effectively fluidized both the epidermis and dermis of the skin, potentially increasing drug permeability and retention. The application of Tween 80 and PEG 400, on the other hand, significantly enhanced these effects, as these are well known penetration enhancers. After 24 h, an average of 70.78 ± 5.8 μg/cm2 of methotrexate was permeated from the nanoemulsion gel with a flux value of 2.078 ± 0.42 μg/cm2/h, according to permeation measurements. Finally, in vivo experiments on rabbit skin revealed that the increased skin penetration of methotrexate-loaded nanoemulsion gel was not due to structural alterations in intercellular lipid layers in the stratum corneum. In vivo antipsoriatic studies on rats revealed that MTX NEG produced a PASI decrease that was extremely similar and even better than the 91% reduction seen in the MTX tablet group. According to the pharmacokinetic profile, Cmax was 8.5 μg/mL, Tmax was 12 h, and t1/2 was 15.5 ± 2.37 h. These findings reinforce that MTX-NEG based on olive oil could be a possible treatment for psoriasis and could decrease the remission of psoriasis-like symptoms.

scholarly journals FORMULATION AND OPTIMIZATION OF BUOYANT IN SITU GELLING SYSTEM OF VALSARTAN USING NATURAL POLYMER

2017 ◽  
Vol 9 (10) ◽  
pp. 128
Author(s):  
S. Prasanthi ◽  
M. Vidyavathi
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
Natural Polymer ◽  
Natural Polymers ◽  
Independent Variables ◽  
Drug Release Kinetics ◽  
Ftir Studies

Objective: Currently natural polymers have wide spread importance in fabrication of controlled drug delivery systems. Hence in this study ocimum basilicum mucilage, (OBM) a natural polymer used to know its effect as polymer alone and in combination with HPMC K15M and Guargum in oral in situ floating gel of Valsartan using 3 full level factorial design.Methods: FTIR studies conducted to know major drug polymer interactions. OBM, HPMC K15M and Guargum were chosen as three independent variables and examined at 3 levels for in vitro buoyancy (Y1) and drug release at 10 h (Y2) as responses. By using mathematical model approach formulation variables were quantitatively evaluated, and optimized formulation (VFIG) subjected for in vitro buoyancy, density, pH, in vitro drug release, drug content, gelling capacity and drug release kinetics. In addition VFIG studied for In vivo buoyancy and release kinetics.Results: FTIR studies revealed that excipients were compatible with drug. ANOVA results shown that independent variables have significant effect (p<0.05) on both the responses. Observed responses of optimized formulation (3 % OBM, 0.88 % HPMC and 1.25 % Guar gum) were in good agreement with the experimental values. Results of all in vitro evaluations lies within the limits and drug release kinetics followed non-fickian diffusion mechanism. In vivo buoyancy study in rabbit evidenced floatation for>8 h and in vivo pharmacokinetic study exhibited increased bioavailability of optimized formulation.Conclusion: Prepared VFIG with optimized concentrations of OBM, HPMC K15M and Guargum exploiting as a promising dosage form for enhanced gastric delivery.

scholarly journals Probiotic Associated Therapeutic Curli Hybrids (PATCH)

2018 ◽  
Author(s):  
Pichet Praveschotinunt ◽  
Anna M. Duraj-Thatte ◽  
Ilia Gelfat ◽  
Franziska Bahl ◽  
David B. Chou ◽  
...  
Keyword(s):  
Barrier Function ◽  
Unmet Need ◽  
Intestinal Barrier ◽  
Genetically Engineered ◽  
Intestinal Barrier Function ◽  
Beneficial Bacteria ◽  
Fibrous Matrix

AbstractThere is an unmet need for new treatment methods for inflammatory bowel disease (IBD) that can reliably maintain remission without leading to detrimental side effects. Beneficial bacteria have been utilized as an alternative treatment for IBD albeit with low efficacy. We genetically engineered Escherichia coli Nissle 1917 (EcN) to create an anti-inflammatory fibrous matrix in situ. This matrix consists of EcN-produced curli nanofibers displaying trefoil factors (TFFs), known to promote intestinal barrier function and epithelial restitution. We confirmed that engineered EcN was able to secrete the curli-fused TFFs in vitro and in vivo, and was non-pathogenic. We observed an enhanced protective effect of engineered EcN against dextran sodium sulfate induced colitis in mice, associated with barrier function reinforcement and immunomodulation. This work sets the foundation for the development of a novel therapeutic platform in which the in situ production of a therapeutic protein matrix from beneficial bacteria can be exploited.

Formulation and Evaluation of Flurbiprofen Solid Dispersions Incorporated Buccal Patches

2020 ◽  
pp. 674-681
Author(s):  
Mohammed Jaffer Sadik ◽  
Abdulla Khan
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Release ◽  
Solid Dispersion ◽  
Release Kinetics ◽  
Solid Dispersions ◽  
Methyl Cellulose ◽  
Sustained Drug Release ◽  
Casting Technique ◽  
Zero Order Release

Flurbiprofen is an anti-inflammatory drug used in treating rheumatoid arthritis and ankylosing spondylitis. The present work is aimed at overcoming the deprived solubility of flurbiprofen by solid dispersion (SD) technique. The current paper is  the continuance of the published solid dispersion by considering the best final optimized formulation containing flurbiprofen drug: AQOAT AS: SLS as drug: polymer: surfactant in 1:5:2 ratios, and incorporating it into buccal patches to overcome the gastric side effect and attaining  sustained drug release. In this study 15 buccal patches  were formulated  by adopting  solvent casting technique  using polymers like polyvinyl hydroxyethylcellulose (HEC), hydroxypropryl methyl cellulose E15 (HPMC E15), polyvinyl pyrrolidone (PVP), carbopol and analyzed  for the drug content, drug  diffusion, in-vivo dissolution  and stability studies. All SD loaded patches displayed superior drug release (95% to 99.96%) over 12 h. The formulation BP14 showed excellent drug release extended over 12 h with drug release of 99.96% whereas marketed formulation which is sustained release Tablet showed 96.86% drug release within 6 h. The drug release kinetics show that the buccal patches follow zero order release kinetics with correlation coefficient (R2) ranging between 0.905-0.971 and BP14 formulation shown best R2 value. All the formulations exhibited best fit to Higuchi model with R2 ranging between 0.9911 – 0.9962 indicating drug release by diffusion process. The results conclude that buccal patches are superior alternatives for flurbiprofen that facilitates enhanced drug release for prolonged period of time in the effective management of rheumatoid arthritis.

scholarly journals Oxo-M and 4-PPBP Delivery via Multi-Domain Peptide Hydrogel Toward Tendon Regeneration

2021 ◽  
Author(s):  
Ga Young Park ◽  
Solaiman Tarafder ◽  
Samantha Lewis ◽  
Soomin Park ◽  
Ryunhyung Park ◽  
...  
Keyword(s):  
Small Molecules ◽  
Release Kinetics ◽  
Tendon Healing ◽  
Tendon Regeneration ◽  
Tenogenic Differentiation ◽  
Domain Peptide ◽  
Kinetics Of

AbstractWe have recently identified novel small molecules, Oxo-M and 4-PPBP, which specifically stimulates endogenous tendon stem/progenitor cells (TSCs) leading to potential regenerative healing of fully-transected tendons. Here we investigated an injectable, multi-domain peptide (MDP) hydrogel providing a controlled delivery of the small molecules for regenerative tendon healing. We investigated the release kinetics of Oxo-M and 4-PPBP from MDP hydrogels and the effect of MDP-released small molecules on tenogenic differentiation of TSCs and in vivo tendon healing. In vitro, MDP showed a sustained release of Oxo-M and 4-PPBP and a slower degradation compared to fibrin. In addition, tenogenic gene expression was significantly increased in TSC with MDP-released Oxo-M and 4-PPBP as compared to the fibrin-released. In vivo, MDP releasing Oxo-M and 4-PPBP significantly improved tendon healing, likely associated with prolonged effects of Oxo-M and 4-PPBP on suppression of M1 macrophages and promotion of M2 macrophages. Comprehensive analyses including histomorphology, digital image processing, and modulus mapping with nanoindentation consistently suggested that Oxo-M and 4-PPBP delivered via MDP further improved tendon healing as compared to fibrin-based delivery. In conclusion, MDP delivered with Oxo-M and 4-PPBP may serve as an efficient regenerative therapeutic for in situ tendon regeneration and healing.

RESEALED ERYTHROCYTES: A PROMISING APPROACH TO ENHANCE EFFICACY OF ANTICANCER DRUGS

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (03) ◽  
pp. 9-20
Author(s):  
◽  
Prathibha Salve ◽  
Rajendra Doijad ◽  
Niranjan Chivate
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Anticancer Drugs ◽  
Delivery System ◽  
Release Kinetics ◽  
Drug Loading ◽  
The Body ◽  
Zero Order Release

Targeted drug delivery system is a potential drug delivery system which delivers the drug to particular organ of interest only. This improves the therapeutic efficacy of the treatment by reducing the side effects of drug which are required in case of anticancer drugs. Erythrocytes have been the most interesting carrier and have found to possess great potential in drug targeting. Resealed erythrocytes are gaining more popularity because of their ability to circulate throughout the body, biocompatibility, zero order release kinetics, reproducibility and ease of preparation. In this review, we have made an attempt to understand the process in detail to prepare resealed erythrocytes, including its mechanism, source and isolation of erythrocytes, methods of drug loading, in vivo and in vitro characterization of resealed erythrocytes, with special emphasis on applications of resealed erythrocytes for cancer treatment. With this review we can conclude that resealed erythrocyte is a promising approach to enhance efficacy of anticancer drugs.

scholarly journals AAPH or Peroxynitrite-Induced Biorelevant Oxidation of Methyl Caffeate Yields a Potent Antitumor Metabolite

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1537
Author(s):  
Laura Fási ◽  
Ahmed Dhahir Latif ◽  
István Zupkó ◽  
Sándor Lévai ◽  
Miklós Dékány ◽  
...  
Keyword(s):  
Antitumor Agent ◽  
Hydroxycinnamic Acids ◽  
Diversity Oriented Synthesis ◽  
Formation Reaction ◽  
Biologically Relevant ◽  
Strong Antitumor Activity ◽  
Methyl Caffeate

Hydroxycinnamic acids represent a versatile group of dietary plant antioxidants. Oxidation of methyl-p-coumarate (pcm) and methyl caffeate (cm) was previously found to yield potent antitumor metabolites. Here, we report the formation of potentially bioactive products of pcm and cm oxidized with peroxynitrite (ONOO¯), a biologically relevant reactive nitrogen species (RNS), or with α,α′-azodiisobutyramidine dihydrochloride (AAPH) as a chemical model for reactive oxygen species (ROS). A continuous flow system was developed to achieve reproducible in situ ONOO¯ formation. Reaction mixtures were tested for their cytotoxic effect on HeLa, SiHa, MCF-7 and MDA-MB-231 cells. The reaction of pcm with ONOO¯ produced two fragments, an o-nitrophenol derivative, and a new chlorinated compound. Bioactivity-guided isolation from the reaction mixture of cm with AAPH produced two dimerization products, including a dihydrobenzofuran lignan that exerted strong antitumor activity in vitro, and has potent in vivo antimetastatic activity which was previously reported. This compound was also detected from the reaction between cm and ONOO¯. Our results demonstrate the ROS/RNS dependent formation of chemically stable metabolites, including a potent antitumor agent (5), from hydroxycinnamic acids. This suggests that diversity-oriented synthesis using ROS/RNS to obtain oxidized antioxidant metabolite mixtures may serve as a valid natural product-based drug discovery strategy.

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