scholarly journals Development of Budesonide Loaded Biopolymer Based Dry Powder Inhaler: Optimization, In Vitro Deposition, and Cytotoxicity Study

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Ashwin J. Mali ◽  
Atmaram P. Pawar ◽  
Ravindra N. Purohit
Keyword(s):  
Side Effects ◽  
Active Site ◽  
Lung Diseases ◽  
Dry Powder Inhaler ◽  
Deposition Efficiency ◽  
Therapeutic Delivery ◽  
Drug Molecules ◽  
Systemic Side Effects ◽  
The Subject

The progress in the development of DPI technology has boosted the use of sensitive drug molecules for lung diseases. However, delivery of these molecules from conventional DPI to the active site still poses a challenge with respect to deposition efficiency in the lung. At same time, serious systemic side effects of drugs have become a cause for concern. The developed budesonide loaded biopolymer based controlled release DPI had shown maximum in vitro lung deposition with least toxicity. The subject of present study, lactose-free budesonide loaded biopolymer based DPI, further corroborates the great potential of antiasthmatic drugs. This technology is expected to revolutionize the approaches towards enhanced therapeutic delivery of prospective drugs.

scholarly journals Albumin-Albumin/Lactosylated Core-Shell Nanoparticles: Therapy to Treat Hepatocellular Carcinoma for Controlled Delivery of Doxorubicin

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5432
Author(s):  
Nayelli Guadalupe Teran-Saavedra ◽  
Jose Andrei Sarabia-Sainz ◽  
Enrique Fernando Velázquez-Contreras ◽  
Gabriela Ramos-Clamont Montfort ◽  
Martín Pedroza-Montero ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Side Effects ◽  
Hepg2 Cells ◽  
Core Shell ◽  
Shell Nanoparticles ◽  
Human Liver Cancer ◽  
Systemic Side Effects ◽  
Human Liver Cancer Cells ◽  
Core Shell Nanoparticles

Doxorubicin (Dox) is the most widely used chemotherapeutic agent and is considered a highly powerful and broad-spectrum for cancer treatment. However, its application is compromised by the cumulative side effect of dose-dependent cardiotoxicity. Because of this, targeted drug delivery systems (DDS) are currently being explored in an attempt to reduce Dox systemic side-effects. In this study, DDS targeting hepatocellular carcinoma (HCC) has been designed, specifically to the asialoglycoprotein receptor (ASGPR). Dox-loaded albumin-albumin/lactosylated (core-shell) nanoparticles (tBSA/BSALac NPs) with low (LC) and high (HC) crosslink using glutaraldehyde were synthesized. Nanoparticles presented spherical shapes with a size distribution of 257 ± 14 nm and 254 ± 14 nm, as well as an estimated surface charge of −28.0 ± 0.1 mV and −26.0 ± 0.2 mV, respectively. The encapsulation efficiency of Dox for the two types of nanoparticles was higher than 80%. The in vitro drug release results showed a sustained and controlled release profile. Additionally, the nanoparticles were revealed to be biocompatible with red blood cells (RBCs) and human liver cancer cells (HepG2 cells). In cytotoxicity assays, Dox-loaded nanoparticles decrease cell viability more efficiently than free Dox. Specific biorecognition assays confirmed the interaction between nanoparticles and HepG2 cells, especially with ASGPRs. Both types of nanoparticles may be possible DDS specifically targeting HCC, thus reducing side effects, mainly cardiotoxicity. Therefore, improving the quality of life from patients during chemotherapy.

scholarly journals Retinoic Acid-Containing Liposomes for the Induction of Antigen-Specific Regulatory T Cells as a Treatment for Autoimmune Diseases

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1949
Author(s):  
Daniëlle ter Braake ◽  
Naomi Benne ◽  
Chun Yin Jerry Lau ◽  
Enrico Mastrobattista ◽  
Femke Broere
Keyword(s):  
Retinoic Acid ◽  
Side Effects ◽  
Inflammatory Diseases ◽  
Current Treatment ◽  
Chronic Inflammatory Diseases ◽  
All Trans Retinoic Acid ◽  
Tolerogenic Dendritic Cells ◽  
Systemic Side Effects ◽  
Targeted Approach

The current treatment of autoimmune and chronic inflammatory diseases entails systemic immune suppression, which is associated with increased susceptibility to infections. To restore immune tolerance and reduce systemic side effects, a targeted approach using tolerogenic dendritic cells (tolDCs) is being explored. TolDCs are characterized by the expression of CD11c, the major histocompatibility complex (MHC)II and low levels of co-stimulatory molecules CD40 and CD86. In this study, tolDCs were generated using a human-proteoglycan-derived peptide (hPG) and all-trans retinoic acid (RA). RA-tolDCs not only display a tolerogenic phenotype but also can induce an antigen-specific regulatory T cell (Treg) response in vitro. However, further analysis showed that RA-tolDCs make up a heterogeneous population of DCs, with only a small proportion being antigen-associated tolDCs. To increase the homogeneity of this population, 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG)-containing liposomes were used to encapsulate the relevant antigen together with RA. These liposomes greatly enhanced the proportion of antigen-associated tolDCs in culture. In addition, in mice, we showed that the liposomal co-delivery of antigen and RA can be a more targeted approach to induce antigen-specific tolerance compared to the injection of RA-tolDCs, and that these liposomes can stimulate the generation of antigen-specific Tregs. This work highlights the importance of the co-delivery of an antigen and immunomodulator to minimize off-target effects and systemic side effects and provides new insights in the use of RA for antigen-specific immunotherapy for autoimmune and chronic inflammatory diseases.

scholarly journals GAMBARAN LAMA PENGGUNAAN KB SUNTIK PROGESTIN DENGAN KEJADIAN AMENORRHEA SEKUNDER DI DUSUN KARANGLO DESA DRIYOREJO GRESIK

2016 ◽  
Vol 1 (1) ◽  
pp. 8
Author(s):  
Titin Eka Nuriyanah ◽  
Windi Suryaning Rejeki
Keyword(s):  
Side Effects ◽  
Service Providers ◽  
Field Extension ◽  
The Body ◽  
Secondary Amenorrhea ◽  
Injectable Contraceptive ◽  
Study Population ◽  
Systemic Side Effects ◽  
The Subject ◽  
Descriptive Method

Injectable contraceptive is a contraceptive method with many side effects, hormonal injectables have away of working systemically in the body, causing systemic side effects on the body as well. Based on the results of the BKKBN and PLKB(Field Extension Family Planning) Driyorejo’s village injectables users is quite high compared to other contraceptives. The purpose of this studyw as to determine the old picture with the use of progestin injectables incidence of secondary amenorrhea.The design of this research is descriptive method. The study population was all acceptors progestin’s injection in the hamlet of Karanglo Driyorejo’s village-Gresik of 18 acceptors.The entire population can be the subject of research. Data were collected byi nterview using the interview guidelines.The results of this study indicate that the majority of acceptors progestin injectables using progestin injectables for > 1 year by 80 %. The majority of acceptors progestin injectables contraception experiencing secondary amenorrhea by 75 %. Most of the acceptors were using progestin injectables ≤ 1 year of amenorrhea is not having by 100 %Conclusion research that most acceptors progestin injectables > 1 year experience secondary amenorrhea. It is recommended that the ministry, in particular midwives improve counseling and information to each acceptor progestin injectables especially about the possible side effects so there is no misunderstanding between service providers and service recipients.

Antileishmanial and Antitrypanosomal Activity of Triterpene Derivatives from Latex of Two Euphorbia Species

2011 ◽  
Vol 66 (7-8) ◽  
pp. 360-366 ◽  
Author(s):  
Noureddine Mazoir ◽  
Ahmed Benharref ◽  
María Bailén ◽  
Matías Reina ◽  
Azucena González-Coloma ◽  
...  
Keyword(s):  
Side Effects ◽  
Leishmania Infantum ◽  
Mammalian Cells ◽  
New Drugs ◽  
Medical Applications ◽  
In Vitro Activity ◽  
Chemical Modifications ◽  
Selective Toxicity ◽  
The Subject

The in vitro activity on Leishmania infantum promastigotes and Trypanosoma cruzi epimastigotes of 25 semisynthetic terpenoid derivatives has been evaluated. These compounds were obtained through chemical modifications of the major components of Euphorbia resinifera (α-euphol and α-euphorbol) and Euphorbia officinarum (obtusifoliol and 31-norlanosterol). Leishmaniasis and Chagas´ disease are major worldwide health problems. The drugs of choice for their treatment are still problematic in both cases, and therefore there is an urgent need to discover new drugs with high activity and low side effects. Natural products have become a key source of new drugs in the last years. The genus Euphorbia has been the subject of abundant phytochemical and pharmacological research because of its potential medical applications, but the antiparasitic effects of derivatives from plants of this genus are still unknown. Our results showed that 76% and 64% of the test compounds had antiparasitic effects on L. infantum and T. cruzi, respectively. The different activities on both parasites, especially their moderate effects on mammalian cells, indicate an interesting selective toxicity.

scholarly journals Viscosified Solid Lipidic Nanoparticles Based on Naringenin and Linolenic Acid for the Release of Cyclosporine A on the Skin

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3535
Author(s):  
Sonia Trombino ◽  
Camilla Servidio ◽  
Annarita Stella Laganà ◽  
Filomena Conforti ◽  
Mariangela Marrelli ◽  
...  
Keyword(s):  
Side Effects ◽  
Linolenic Acid ◽  
Skin Permeation ◽  
Systemic Absorption ◽  
Psoriasis Treatment ◽  
Potential Applications ◽  
In Vitro Skin Permeation ◽  
Systemic Side Effects ◽  
Lipophilicity Potential

Psoriasis is one of the most common human skin disorders. Although its pathogenesis is complex and not completely know, the hyperactivation of the immune system seem to have a key role. In this regard, among the most effective systemic therapeutics used in psoriasis, we find cyclosporine, an immunosuppressive medication. However, one of the major problems associated with the use of cyclosporine is the occurrence of systemic side effects such as nephrotoxicity, hypertension, etc. The present work fits in this context and its aim is the design of suitable platforms for cyclosporine topical release in psoriasis treatment. The main objective is to achieve local administration of cyclosporine in order to reduce its systemic absorption and, consequently, its side effects. In order to improve dermal penetration, solid lipid nanoparticles (SLNs) are used as carriers, due to their lipophilicity and occlusive properties, and naringenin and linolenic acid are chosen, due to their properties, as starting materials for SLNs design. In order to have dermatological formulations and further modulate drug release, SLNs are incorporated in several topical vehicles obtaining gels with different degree of lipophilicity. Potential applications for psoriasis treatment were evaluated by considering the encapsulation efficiency, release profiles, in vitro skin permeation, and anti-inflammatory effects.

scholarly journals Anti-Inflammatory Effect of Very High Dose Local Vessel Wall Statin Administration: Poly(L,L-Lactide) Biodegradable Microspheres with Simvastatin for Drug Delivery System (DDS)

2021 ◽  
Vol 22 (14) ◽  
pp. 7486
Author(s):  
Piotr Wacinski ◽  
Mariusz Gadzinowski ◽  
Wojciech Dabrowski ◽  
Justyna Szumilo ◽  
Jakub Wacinski ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Delivery System ◽  
Delivery System ◽  
Vessel Wall ◽  
Systemic Side Effects ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Atherosclerosis involves an ongoing inflammatory response of the vascular endothelium and vessel wall of the aorta and vein. The pleiotropic effects of statins have been well described in many in vitro and in vivo studies, but these effects are difficult to achieve in clinical practice due to the low bioavailability of statins and their first-pass metabolism in the liver. The aim of this study was to test a vessel wall local drug delivery system (DDS) using PLA microstructures loaded with simvastatin. Wistar rats were fed high cholesterol chow as a model. The rat vessels were chemically injured by repeated injections of perivascular paclitaxel and 5-fluorouracil. The vessels were then cultured and treated by the injection of several concentrations of poly(L,L-lactide) microparticles loaded with the high local HMG-CoA inhibitor simvastatin (0.58 mg/kg) concentration (SVPLA). Histopathological examinations of the harvested vessels and vital organs after 24 h, 7 days and 4 weeks were performed. Microcirculation in mice as an additional test was performed to demonstrate the safety of this approach. A single dose of SVPLA microspheres with an average diameter of 6.4 μm and a drug concentration equal to 8.1% of particles limited the inflammatory reaction of the endothelium and vessel wall and had no influence on microcirculation in vivo or in vitro. A potent pleiotropic (anti-inflammatory) effect of simvastatin after local SVPLA administration was observed. Moreover, significant concentrations of free simvastatin were observed in the vessel wall (compared to the maximum serum level). In addition, it appeared that simvastatin, once locally administered as SVPLA particles, exerted potent pleiotropic effects on chemically injured vessels and presented anti-inflammatory action. Presumably, this effect was due to the high local concentrations of simvastatin. No local or systemic side effects were observed. This approach could be useful for local simvastatin DDSs when high, local drug concentrations are difficult to obtain, or systemic side effects are present.

scholarly journals Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in Mice

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 154 ◽  
Author(s):  
Hua Wang ◽  
Lifeng Xiao ◽  
Jianguo Tao ◽  
Venkat Srinivasan ◽  
Brendan Boyce ◽  
...  
Keyword(s):  
Side Effects ◽  
Proteasome Inhibitor ◽  
Tumor Burden ◽  
Novel Therapies ◽  
Common Cancer ◽  
Discontinuation Of Treatment ◽  
Systemic Side Effects ◽  
Novel Therapeutic

Multiple myeloma (MM) is the most common cancer affecting the bone and bone marrow and remains incurable for most patients; novel therapies are therefore needed. Bortezomib (Btz) is an FDA-approved drug for the treatment of patients with MM. However, its severe side effects require a dose reduction or the potential discontinuation of treatment. To overcome this limitation, we conjugated Btz to a bisphosphonate (BP) residue lacking anti-osteoclastic activity using a novel chemical linker and generated a new bone-targeted Btz-based (BP-Btz) proteasome inhibitor. We demonstrated that BP-Btz, but not Btz, bound to bone slices and inhibited the growth of MM cells in vitro. In a mouse model of MM, BP-Btz more effectively reduced tumor burden and bone loss with less systemic side effects than Btz. Thus, BP-Btz may represent a novel therapeutic approach to treat patients with MM.

scholarly journals Developing inhaled protein therapeutics for lung diseases

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Abigail A. Matthews ◽  
Pui Lai Rachel Ee ◽  
Ruowen Ge
Keyword(s):  
Side Effects ◽  
Protein Stability ◽  
Potential Risk ◽  
Lung Diseases ◽  
Structural Changes ◽  
Systemic Circulation ◽  
Protein Therapeutics ◽  
Inhalation Device ◽  
Drug Deposition ◽  
Systemic Side Effects

Abstract Biologic therapeutics such as protein/polypeptide drugs are conventionally administered systemically via intravenous injection for the treatment of diseases including lung diseases, although this approach leads to low target site accumulation and the potential risk for systemic side effects. In comparison, topical delivery of protein drugs to the lung via inhalation is deemed to be a more effective approach for lung diseases, as proteins would directly reach the target in the lung while exhibiting poor diffusion into the systemic circulation, leading to higher lung drug retention and efficacy while minimising toxicity to other organs. This review examines the important considerations and challenges in designing an inhaled protein therapeutics for local lung delivery: the choice of inhalation device, structural changes affecting drug deposition in diseased lungs, clearance mechanisms affecting an inhaled protein drug’s lung accumulation, protein stability, and immunogenicity. Possible approaches to overcoming these issues will also be discussed.

Ancylostoma caninum Anticoagulant Peptide Blocks Metastasis In Vivo and Inhibits Factor Xa Binding to Melanoma Cells In Vitro

1998 ◽  
Vol 79 (05) ◽  
pp. 1041-1047 ◽  
Author(s):  
Kathleen M. Donnelly ◽  
Michael E. Bromberg ◽  
Aaron Milstone ◽  
Jennifer Madison McNiff ◽  
Gordon Terwilliger ◽  
...  
Keyword(s):  
Active Site ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Melanoma Cells ◽  
Factor V ◽  
Ancylostoma Caninum ◽  
Metastatic Activity

SummaryWe evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP’s anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme’s active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP’s antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

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