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Magnetically Controlled Targeted Chemotherapy
Published in Neville Willmott, John Daly, Microspheres and Regional Cancer Therapy, 2020
One of the important characteristics of an ideal targetable drug delivery system is its ability to traverse the target tissue endothelium and release the included chemotherapeutic agent at cellular and/or subcellular level.19,20 Indeed, it is also essential that the pharmacodynamic characteristics of the drug are not altered at any stage prior to reaching the target cells.13 Although some studies have suggested the possibility of extravascular transport of submicron drug carriers through the vasculature of malignant tumor tissue due to their increased permeability,45 from the therapeutic’s standpoint, extremely small fractions of the administered dose of drug carrier ever reaches the target tissue interstitium. Even with monoclonal antibody-based delivery systems, the peak drug concentrations in tumor tissue are rarely 2- to 3-fold higher than the surrounding normal tissues.46 In most instances the majority of carrier-delivered drug or macromolecular-conjugated drug is efficiently removed by the RES. Contrary to this standard in vivo deposition pattern, magnetic drug delivery systems offer unique characteristics in that they minimize drug carrier uptake by RES, facilitate its extravasation across the target tissue vasculature, and thus increase the probability of intracellular or third-order drug targeting.19,43,45,47,48
The science of biotechnology
Published in Ronald P. Evens, Biotechnology, 2020
Also, specialized biotechnology-related molecular manipulation and formulations have been employed to enhance product delivery, which has been done for liposomes and polymers. Liposomes are biological molecules comprised usually of layers of lipids with a drug or biological incorporated into the center or a specific layer in the liposome structure. The goal is improved drug delivery to and activity in tissues because of the carrier function and lipid nature of the liposome, which in association with the lipid cell walls of the target tissue fosters more penetration into cells. Pegylation of the liposomal molecule is often used as well, to reduce potential immunogenicity of the product. Hopefully, adverse events from off-target tissue activity can be reduced through liposomes or pegylation. Polymers serve as carriers of a drug or biological to enhance product delivery to the tissue site, for example, a carmustine-polymer product allows placement of a cancer drug in the brain post-surgery.
Farnesyltransferase Inhibitors: Current and Prospective Development for Hematologic Malignancies
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Hematologic malignancies provide a fertile testing ground for antitumor agents because of the relative ease with which tumor tissue can be obtained throughout the therapeutic course. The ability to obtain target tissue in a longitudinal fashion provides a unique opportunity to define the relevant molecular components that may be modulated by these compounds and to relate those molecular effects to the clinical outcome. At present, there are three nonpeptidomimetic FTIs being tested clinically in a broad spectrum of hematologic malignancies: tipifarnib (R115777, Zarnestra), lonafarnib (SCH66336), and BMS-214662. Tipifarnib and lonafarnib are given orally, whereas BMS-214662 is administered intravenously because of dose-dependent gastrointestinal toxicities. To date, all three exhibit clinical and molecular biologic activities in diverse myeloid malignancies and MM with modest and acceptable toxicities (Table 2).
Low-intensity ultrasound promotes uterine involution after cesarean section: the first multicenter, randomized, controlled clinical trial
Published in International Journal of Hyperthermia, 2022
Yi Qin, Xiaobo Zhao, Xiaojing Dong, Juntao Liu, Longqiong Wang, Xiaohua Wu, Bin Peng, Chengzhi Li
Ultrasound is a kind of mechanical wave with a frequency of above 20 kHz [21,22], which has good tissue penetration, positioning performance and energy deposition. In addition, it can penetrate the surface tissue and focus on the target tissue at a specific depth to produce biological effects. Depending on the sound energy applied, ultrasonic waves can produce thermal or non-thermal effects, both of which have their own application ranges. Through instant hyperthermia, coagulation necrosis, protein denaturation, and cell apoptosis appear in the tissues in the target area [23]. High-intensity ultrasound does not damage the normal tissues around the target area, which is mainly used in the treatment of solid tumors, such as gynecological tumors [24,25]. LIUS is a kind of ultrasound with low frequency and intensity. That mainly provides non-thermal effects, including cavitation, mechanical stimulation and shock waves [26]. It is not destructive and is often used to promote bone healing [27], cartilage healing and regeneration [28], inflammation inhibition [29]. Moreover, LIUS has been clinically proven effective in promoting uterine contractions. However, its underlying mechanisms have not been fully depicted.
Nerve Growth Factor as an Ocular Therapy: Applications, Challenges, and Future Directions
Published in Seminars in Ophthalmology, 2021
Poor stability also affects the ability of NGF to exert effects on target tissue. rhNGF becomes unstable in plasma at physiologic temperatures after approximately four days.95 Pharmacokinetic studies of rhNGF have found that after subcutaneous injections, the molecule achieves wide distribution, preferentially to highly perfused and neuronal cell types throughout the body.96 Because of extensive protein redistribution as well as enzymatic degradation, even delivering the drug directly to the target tissue may be limited in long-term effect. For example, in a study of an intracranial polymeric rhNGF delivery system, drug concentration in brain tissue decreased exponentially with distance from the device, and tissue half-life was estimated at approximately 1.7 hours.97 NGF in topical eye drops permeates into various ocular tissues, including the cornea, retina, and optic nerve, and even reaches tissue as distant as neurons in the forebrain.30,98 However, peak levels of NGF are seen six hours after administration, necessitating frequent administration to achieve a desired local effect.99 Stability and duration of effect are reflected in the dosage instructions for Oxervate™, which require eye drop administration six times daily.
Recent advances in the combination delivery of drug for leukemia and other cancers
Published in Expert Opinion on Drug Delivery, 2020
Thikrayat Al-Attar, Sundararajan V. Madihally
When individual drugs are used, it has been recognized that higher doses are required, which carries the burden of side effects. An approach to reducing the dosage is to explore a combination of two drugs with the intent of reducing the dosage of each drug. One drug can be administrated systemically in series with local drug delivery, where cells are primed for the targeted treatment [78]. When selecting a delivery method, it is advantageous to consider the following steps: Define the target tissue/organ/cells, and have an understanding of the target microenvironment.Define the chemical and physical properties- such as molecular weight, size, charge, and hydrophilicity of the therapeutic agents.Select the required scale; nanosystems or microsystems can be selected based on medical needs, drug loading requirements, and level of release control.