Explore chapters and articles related to this topic
Exosomes in Cancer Disease, Progression, and Drug Resistance
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Taraka Sai Pavan Grandhi, Rajeshwar Nitiyanandan, Kaushal Rege
Morse et al. [120] used dendritic cells isolated from peripheral blood mononuclear cells (PBMCs) of late stage non-small cell lung cancer patients to derive exosomes expressing MAGE A3 (class 1 or class 2), A4, A10, or control peptides. The patients were injected weekly twice with different treatment conditions consisting of a mixture of exosomes manufactured previously. The patients were separated into three cohorts: A (MAGE A3, A4, A10, CMV and tetanus toxoid), B (MAGE A3, A4, A10, A3 class 2, CMV and tetanus toxoid), and C (MAGE A3 class I and class II, A4 and A10). The immune response triggered by these peptides was studied and was observed to primarily mediate a NK cell response rather than a T-cell response (Fig. 7.10), likely because of T-regulatory cell activity. Survival of the patients from different cohorts was found to be in a range of 52–309 days in the case of cohort A, 280 more than 665 days in the case of cohort B and 244 to 502 days in the case of cohort C. The researchers concluded that an extended stabilization of the disease was observed in patients as compared to regular treatments in which case the disease progressed within 3 months. This small trial also showed the practicality of producing these exosomes from patient PBMCs and the efficacy of such treatments in human patients.
Poly(Alkyl Cyanoacrylate) Nanoparticles for Delivery of Anti-Cancer Drugs
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
R. S. R. Murthy, L. Harivardhan Reddy
Birrenbach and Speiser5 described the polymerization process for the preparation of hydrophilic micelles containing solubilized drug molecules including labile proteins in a colloidal aqueous system of dissolved monomers. The hydrocarbon medium constituted the outer phase. After secondary solubilization with the aid of selected surfactants, the polymerization of micelles under different conditions was performed. The entrapped tagged material (human 125I-immunoglobulin G) showed a stable fixation in the nanoparticles during long-term in vitro liberation trials. Nanoparticles were spherical in shape, 80 nm in diameter, and embedded with antigenic material (tetanus toxoid and human immunoglobulin G) for parenteral use. These preparations showed intact biological activity and high antibody production in animals.
Biologic Drug Substance and Drug Product Manufacture
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Ajit S. Narang, Mary E. Krause, Shelly Pizarro, Joon Chong Yee
In lyophilized formulations, the role of residual moisture in protein stability can be complex. The amount of moisture adsorbed on each protein as a monolayer can be determined by the Brunauer-Emmett-Teller method. Lyophilized protein needs a closely bound water layer to shield its highly polar groups, which would otherwise be exposed, leading to aggregation and opalescence upon reconstitution. High moisture content, on the other hand, could increase plasticity in the system leading to high reactivity and compromising the physicochemical stability. For example, insulin, tetanus toxoid, somatotrophin, and human albumin aggregate in the presence of moisture, which can lead to reduced activity, stability, and diffusion.
An effective, simple and low-cost pretreatment for culture clarification in tetanus toxoid production
Published in Preparative Biochemistry and Biotechnology, 2018
Lucía Avila, Osvaldo Cascone, Mirtha Biscoglio, Matías Fingermann
Tetanus toxin, produced by Clostridium tetani, is the responsible of a severe disease known as tetanus.2 This toxin, one of the most potent known, is an heterodimeric protein composed of one heavy chain (100 kDa) linked by a single disulfide bond to a light chain (50 kDa).3 Tetanus still remains a serious threat to public health, with over 200,000 fatal cases per year around the world.4 Chemically inactivated tetanus toxin (tetanus toxoid, TT), produced during the culture of a virulent C. tetani strain, is an active pharmaceutical ingredient (API) of anti-tetanus vaccines.5,6 Tetanus toxin expression during bacterial growth is the consequence of the activation of the lytic cycle of a lysogenized-phage. Biomass removal from the fermented broth is most commonly performed by filtration.7–11 Lowering clarification costs could thus help making a more affordable production of this important API. In this direction, flocculants, a class of materials that favor solid-liquid separation, increase the efficacy of filtration trains without adversely impacting on the recovery of biopharmaceuticals.12–14 Chitosan stands out from other flocculants due to its characteristic low-cost, high accessibility, non-toxicity, and biodegradability.15 Its safety is exemplified by its increasing use as an adjuvant during the development of new vaccine formulations.16,17 In this work, chitosan is assessed for the first time as part of a primary clarification operation, with an aim on reducing membrane filtration needs and therefore the costs for secondary clarification operations, during TT production.