Likewise, data analysis performed simply by Chanan-Khan et al. in the scientific usage of liposomal realtors since 1995, you may still find many disadvantages that limit their selection of applications. This review presents a focused analysis of these limitations, with an emphasis on toxicity to healthy tissues and unfavorable immune responses, to GSK2973980A shed light on key considerations that should be factored into the design and clinical use of liposomal formulations. Keywords:liposomes, toxicity, immunomodulation, cancer, gene and drug delivery == 1. Introduction == Liposomes are vesicular structures composed of one or more concentric lipid bilayers surrounding an aqueous cavity [1,2,3,4]. The bilayers are predominantly composed of phospholipids, where the polar head groups interface with the outer and inner aqueous phases and the hydrophilic tails are sequestered within the bilayer [4]. Since their discovery by Alec Bangham in the 1960s [5,6], liposomes have been studied extensively as drug delivery vehicles due to their capacity to load both hydrophilic and hydrophobic brokers, as well as their high biocompatibility and tunable size, charge, and surface properties [1,2,3,4]. Liposomal encapsulated drugs first reached the clinic in 1995 with the US Food and Drug Administration (FDA)-approval of Doxil (liposomal doxorubicin) for the treatment of AIDS-related Kaposis sarcoma, and Doxil was later approved to treat ovarian cancer and multiple myeloma [7]. Since the FDA approval of Doxil, numerous liposomal formulations have been employed in the clinic for a wide array of applications, including cancer therapeutics, fungal disease treatment, analgesics, photodynamic therapy, and viral vaccine delivery [8,9]. However, despite the increasing prominence of liposomal drugs in the clinic, there is still limited knowledge regarding their toxicological effects on healthy cells and tissues, as well as the immunological responses they can elicit. Phospholipids, the primary building blocks of liposomes, are amphipathic molecules, meaning they have a hydrophilic region (e.g., polar phosphate head) and a hydrophobic section (e.g., non-polar fatty acid tail). When hydrated in an aqueous answer under artificial conditions, phospholipids spontaneously organize into liposomes due to their thermodynamic phase properties and self-assembling characteristics [10]. The physio-biochemical characteristics of liposomes can be altered by altering the types and ratios of phospholipids, as well as incorporating cholesterol into the bilayer and decorating the liposomal surface with polyethylene glycol (PEG). These modifications can have drastic effects on healthy cells and tissues, as well as activate or suppress the immune system. These complex interactions GSK2973980A therefore have immense implications for the clinical use of liposomal formulations and will be discussed in depth later GSK2973980A in this review. Extensive research has been done to develop a variety of techniques to achieve optimized liposome formation and drug loading. Incorporating therapeutic brokers into liposomes can be achieved either during liposome formation (e.g., passive loading) or after liposome formation (e.g., active loading). Passive loading can be further divided into three categories: mechanical dispersion methods, solvent dispersion methods, and detergent removal methods [2,11,12]. Alternatively, active loading can be accomplished by establishing a pH gradient, causing the unionized drugs that penetrate the lipid bilayer to become ionized due to the low GSK2973980A pH within the liposome, resulting in entrapment [13,14]. FDA approval has been granted for both passively loaded liposomal brokers (e.g., Visudyne and Rabbit Polyclonal to RASA3 AmBisome) and actively loaded liposomal brokers (e.g., Doxil, Myocet, and Onivyde) [15]. Most of the clinically used liposome-based products are administered by intravenous (IV) injection, though some are also given by intramuscular injection (e.g., Inflexal V and Epaxal), by epidural injection (e.g., DepoDur), or by intrathecal injection (e.g., Depocyt) [8]. Liposomes are particularly useful for delivering hydrophobic brokers, which otherwise have poor solubility in aqueous solutions and limited bioavailability [16,17]. Verteporfin (also known as benzoporphyrin derivative), for example, is usually a hydrophobic photosensitizer that is used for photodynamic therapy, a light-based therapeutic modality. While verteporfin self-aggregates in aqueous solutions, liposomal verteporfin (marketed as Visudyne) has improved solubility for IV administration and is FDA-approved to treat wet age-related macular degeneration [18,19]. To date, Visudyne is being evaluated in multiple clinical trials for photodynamic therapy of cancer due in part.
