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The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Marveh Rahmati, Saeid Amanpour, Hadiseh Mohammadpour
The size and blood circulation time of NPS as well as vasculature and micro-environment of tumors are the most important factors in passive targeting. This targeting approach could increase the drug bioavailability and efficacy. Indeed, nanodrugs use the differences between normal and tumor vasculature to reach the targeted site. These differences include angiogenic blood vessels which have large gaps in tumor tissues between adjacent endothelial cells. In addition, the vasculature of tumors is leaky and defective, so an increased level of some mediators, such as nitric oxide, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF) and prostaglandins, is secreted. These properties of tumor vasculature are named enhanced permeability and retention (EPR) effect. This effect enables nanodrugs or other macromolecules to accumulate in tumors [55]. The microenvironment surrounding tumor cells are also different from that of normal cells. The fast-growing cancer cells have a high metabolic rate, and the level of oxygen and nutrients is usually not sufficient for them. Therefore, tumor cells depend on glycolysis pathway for their nutrient and energy supply, thus creating an acidic environment. The liposomes are pH sensitive and release their contents into this microenvironment. In addition, cancer cells express and release some unique enzymes, such as matrix metalloproteinases, which are important for the movement and survival of tumor cells [56].
Improved Silymarin Characteristics for Clinical Applications by Novel Drug Delivery Systems
Published in Madhu Gupta, Durgesh Nandini Chauhan, Vikas Sharma, Nagendra Singh Chauhan, Novel Drug Delivery Systems for Phytoconstituents, 2020
Maryam Tabarzad, Fatemeh Ghorbani-Bidkorbeh, Tahereh Hosseinabadi
Successful niosomal formulations containing sorbitan monostearate (Sp 60) or sorbitan monopalmitate (Sp 40) as non-ionic surfactant, and cholesterol were prepared with efficient encapsulation of silymarin that showed spherical shape and a bilayered structure. In vitro biphasic release profiles with an initial fast release followed by a period of slow release were observed. On rats, an in vivo study proved the significantly improved hepatoprotective effect of niosomal formulations. Subcutaneous administration of these formulations might increase drug bioavailability. Histopathological investigation confirmed the safety of these niosomal formulations (El-Ridy et al., 2012).
Bioavailability of inhaled compounds
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Throughout the years, aerosols of therapeutic compounds have been generated from liquid or solid formulations employing nebulizers, metered-dose inhalers (MDIs), and dry powder inhalers (DPIs). The complexity of these formulations has increased over the years, with dry powder formulations affording the use of a wider variety of excipients and methods of preparation, ranging from physical mixtures of micronized drug and lactose to sophisticated particle engineering approaches. The efficiency of aerosol delivery depends on the device, the aerodynamic diameter and size distribution of the aerosol, as well as the site of deposition in the airways. In turn, the site of aerosol deposition is influenced by the extent to which the disease state of the patient has modified the original airway structure, whereas drug residence time and action are contingent on the clearance mechanisms in that region of the lungs. The effects of these factors on drug bioavailability will be discussed in this chapter as well as the methods employed to determine bioavailability and bioequivalence as outlined by the United States Food and Drug Administration (U.S. FDA).
Role of hesperidin and fresh orange juice in altering the bioavailability of beta-blocker, metoprolol tartrate. An in vivo model
Published in Xenobiotica, 2022
Rabiha Salam, Syeda Nayyab Batool Rizvi, Naqi Hussain, Shama Firdous, Muhammad Zaheer, Muhammad Naeem
In recent years drug bioavailability has become a matter of keen interest in the development of drugs. In the nutritional study, the co-administration of fruit juice with a drug has a considerable effect on its bioavailability. Grapefruit juice has significantly altered the bioavailability of a number of drugs including fexofenadine, felodipine, lovastatin, cyclosporin, triazolam, silenafil, talinolol, simvastatin, acebutolol, and buspiron (Bailey et al. 1991; Hukkinen et al. 1995; Yee et al. 1995; Kantola et al. 1998; Lilja, Kivistö, Backman, et al. 1998; Lilja, Kivistö, Neuvonen 1998; Jetter et al. 2002; Schwarz et al. 2005; Lilja et al. 2005a; Glaeser et al. 2007). Orange juice has also been reported to suppress the bioavailability of drugs including ciprofloxacin, fexofenadine, and beta-blockers (celiprolol and atenolol) (Dresser et al. 2002; Neuhofel et al. 2002; Lilja et al. 2004; 2005b). Orange juice consumption does not affect cytochromes P450 activity in vivo (Takanaga et al. 2000). The decreased bioavailability of drugs with orange juice might be due to an indirect effect on OATPs (Organic anion transporting proteins) from enhanced intestinal fluid volume by the non-specific osmotic effects of the solutes. OATPs are the membrane transporter proteins that facilitates the sodium-independent uptake of substrate compounds through the gastrointestinal wall acting in opposing fashion to efflux transporter in the intestines such as p-glycoproteins. However the exact aetiology by which orange juice reduces the bioavailability of drugs is not known.
Sacubitril-valsartan cocrystal revisited: role of polymer excipients in the formulation
Published in Expert Opinion on Drug Delivery, 2021
Yingxi Zhang, Xiaoxiao Du, Hanxun Wang, Zhonggui He, Hongzhuo Liu
Drug solubility/dissolution in the gastrointestinal milieu and the effective permeability through the GI membrane are the two key processes of oral drug absorption [39]. Numerous studies highlighted that overall drug bioavailability might fail to increase even when the formulation improves apparent solubility significantly [46]. It indicated that the approaches with the aim to enhance the solubility of API are often accompanied by apparent permeability decrease, resulting in unexpected oral absorption. Present study demonstrated that the SAC-VAL calcium sodium salt cocrystal significantly enhanced oral absorption of drugs compared with the physical mixture in spite of the trade-off solubility-permeability characters. The excipient HPMC that has been used in Entresto® tablets appeared to decrease the overall oral absorption of cocrystals. Entresto® is recommended to replace angiotensin-converting enzyme inhibitors (ACEIs) to further reduce the risk of heart failure hospitalization and death in patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite of optimal treatment [47]. Unless contraindicated, all symptomatic patients with HFrEF should receive this medication, preferably at target maximally tolerated doses [48]. Elevated oral bioavailability can minimize the necessary dosage, resulting in the improvement of patient compliance and even clinical efficacy.
Nanonization techniques to overcome poor water-solubility with drugs
Published in Expert Opinion on Drug Discovery, 2020
Flávia Lidiane Oliveira Da Silva, Maria Betânia De Freitas Marques, Kelly Cristina Kato, Guilherme Carneiro
Solubility enhancement is then a priority in the pharmaceutical research and many techniques to overcome poor water solubility with drugs, rationally and systematically, have been proposed based on the change in the thermodynamics of the system [19]. According to the fundamental equation of thermodynamics, the thermodynamic binding affinity, defined as the free energy change upon the binding of the drug to its media, is dependent on the binding enthalpy and entropy. Water is the primary source of enthalpy-entropy compensation in the drug-receptor binding process, once it is the first contact of the drug in the physiological medium [20]. Therefore, except for intravenous formulations, the first limiting step to the drug bioavailability is the solubility in the physiological aqueous media.