Liposomes hold great potential as gene and drug delivery vehicles due to their biocompatibility and modular properties, coupled with the major advantage of attenuating the risk of systemic toxicity from your encapsulated therapeutic agent. removal. Additionally, due to the pharmacokinetics of liposomes in blood circulation, drugs can find yourself sequestered in organs of the mononuclear phagocyte system, affecting liver and spleen function. Importantly, liposomal brokers can also stimulate or suppress the immune system depending on their physiochemical properties, such as size, lipid composition, pegylation, and surface charge. Despite the surge in the clinical use of liposomal brokers since 1995, there are still several drawbacks that limit their range of applications. This review presents a focused analysis of these limitations, with an emphasis on ADOS toxicity to healthy tissues and unfavorable immune responses, to shed light on key considerations that should be factored into the design and clinical use of liposomal formulations. activation-related pseudoallergy (CARPA), can be reduced by slowing the rate of infusion, diluting the Doxil dose, or premedicating with a corticosteroid . In a 4-patient study, grade 3 HSR induced by Doxil occurred almost immediately after the start of infusion in all patients and treatment was halted. Premedication with ranitidine and hydroxyzine prior to the resumption of Doxil infusion eliminated HSR in 3 of the 4 patients . Similarly, data analysis performed by Chanan-Khan et al. showed that, on average, 8% of people who received Doxil experienced HSR . Additionally, 3% of refractory ovarian malignancy patients who were pretreated with corticosteroids and antihistamines to minimize adverse reactions still experienced HSR. Chanan-Khan et al. further showed that HSR occurrence can be as high as 45% for patients receiving Doxil. Within this Phase 1 clinical study, 92% of the patients who experienced HSR experienced significantly elevated Plasma SC5b-9 levels . HSR have been suggested to be caused by the liposomal vehicle of Doxil rather than the encapsulated drug, as these reactions are not known to occur with ADOS ADOS standard doxorubicin [161,162]. It should also be noted that other chemotherapies, such as Taxol (paclitaxel), which relies on a formulation vehicle, and carboplatin, are known to cause HSR [176,177]. Using pig models, Szebeni et al. showed that pulmonary hypertension reactions are dependent on the composition, size, and administration method of liposomes . Large, neutral, multilamellar liposomes composed of 1,2-dimyristoyl-< 0.0001) from the 1st through the 3rd cycle of pegylated liposomal doxorubicin in humans . The wide use of PEG in healthcare, hygiene, and beauty products suggests that most patients will likely have pre-existing anti-PEG antibodies , which could potentially impact the degree of ABC in patients. Other parameters that have been shown to impact the ABC of liposomes are lipid dose, with increasing amounts of the prior dose altering the pharmacokinetics of the subsequent injections in a sigmoid manner , liposome composition (with unsaturated lipids causing a more pronounced ABC ), and the time and frequency of injections [192,194,195,207]. 4. Conclusions For two and a half decades, liposomal drug formulations have been administered in the medical center for the treatment of a variety of ailments, ranging from malignancy to fungal disease. They boast an array of Slc4a1 advantageous features, including biocompatibility, tunable properties, and capacity for loading hydrophilic and hydrophobic brokers, making them convenient drug delivery vehicles. However, despite their clinical relevance and therapeutic potential, there is still a scarcity of knowledge regarding the downsides associated with the administration of liposomes. This mini-review presents a summary of existing knowledge regarding such limitations, divided into two main sections: (1) Toxicological Evaluation of Liposomes and their Building Blocks, and (2) Activation of the Immune System. One of the main toxicological concerns is usually that cationic liposomes, which are primarily utilized for nucleic acid delivery, can be harmful to macrophages and reduce their secretion of important immunomodulators. Additionally, following IV injection, liposomes find yourself sequestered in the organs of the MPS, such.