The keywords comprised liposome, synthesis, functionalization, nanoparticle, cancer, chemotherapy, anticancer, stealth, surface, PEGylation, targeting, and nanomedicine.. The consequent accumulation of liposomes in solid tumours provides improvements in drug delivery as there are higher local drug concentrations available [4]. Hydrophilic anticancer drugs entrapped within the aqueous cores of liposomes are released gradually over the span of several hours and days. However, the optimal strategy discovered was first described by scientists in the 1990s. produced diacerein (DN) loaded liposomes (DNL) conjugated with a synthetic analogue of somatostatin as the targeting ligand (SST-DNL). One issue liposomes face includes the premature leakage of liposomal contents prior to uptake and binding at target sites. Due to the short-lived retention associated with liposomes after in vivo administration, several strategies have been implemented to resolve this issue. Various chemical activation approaches such as pH, redox, light, and enzyme have been employed to provide liposomes with stimuli-responsive features [7]. In order to attain targeted delivery of modified liposomes with SPAAC, complementary functional groups are incorporated into cancer cells to provide a target site for azide binding. Drug release occurs once ligands conjugated to liposomes bind to specific target cell receptors via active targeting. This method involves placing MLV into a bath sonicator or disrupting them with the use of a probe sonicator. This is due to the fact that PEG chains form a hydrophilic film comprised of tightly bound water molecules that protect the liposomal surface by repelling serum protein interactions [16, 25, 26]. Similarly, aptamers are promising targeting ligands that can enhance the efficiency of PEGylated-liposomal doxorubicin (PLD). Furthermore, reductions in the biodistribution of liposomes are one of the consequences of clearance [20, 25]. researched the toxicity of doxorubicin-loaded PEGylated liposomes against FR+tumour cells, and they demonstrated that incubated cultures containing targeted doxorubicin-loaded PEGylated liposomes had a 45-fold greater uptake compared to untargeted liposomes [62]. that discovered that liposomes prepared with saturated phospholipids increased drug retention and blood circulation when compared with liposomes prepared with unsaturated phospholipids. As previously mentioned, liposomes encapsulate both hydrophobic and hydrophilic drugs. The encapsulation of drugs in liposomes changes their pharmacokinetics and biodistribution, greatly increasing treatment efficacy and reducing toxic effects. The issues concerning the off-target side effects may be resolved by liposomes as they enhance the pharmacological and pharmacokinetic profile of anticancer drugs [24]. According to a report conducted by Hamilton et al., 90 percent of the final solution produced contained the desired SUV when the first suspension was passed through the orifice again. Therefore, drug release rates are vital aspects of drug delivery [25]. The double emulsion method is analogous to ethanol injection, as it creates liposomes utilizing solvents. Liposomes are small spherically shaped artificial vesicles containing one or more concentric lipid bilayers that encapsulate an aqueous core with particle sizes that range between 30 nanometres and several micrometres (Figure 1). Liposomes enable sustained drug release and produce less systemic toxicity in comparison with free drug [27]. The most widely recognized example is Doxil, which is PLD [15]. Conversely, the hydrophobic fatty acid chains face inwards as they are repelled by water, thus creating a hydrophobic environment. Coupling of DSPE-PEG-MAL micelles with DTT reduced antibodies was achieved via incubation for twenty-four hours at room temperature. Liposomes have been esteemed for their favourable attributes; they provide a wealth of opportunities for their extensive therapeutic pharmaceutical applications as drug delivery systems, particularly in the treatment and diagnosis of cancer. In contrast to the ethanol injection method, the ether injection method requires that phospholipid and cholesterol are dissolved in an ether solution. For these reasons, liposomes are favoured for their advantageous properties as drug delivery systems for the in vitro and in vivo delivery of biologically active substances [26]. A. Rosenkranz, and A. S. Sobolev, Current approaches for improving intratumoral accumulation and distribution of nanomedicines,, R. Fanciullino and J. Ciccolini, Liposome-encapsulated anticancer drugs: still waiting for the magic bullet?, T. Subramani and H. Ganapathyswamy, An overview of liposomal nano-encapsulation techniques and its applications in food and nutraceutical,, J. Gubernator, Active methods of drug loading into liposomes: recent strategies for stable drug entrapment and increasedin vivoactivity,, L. Sercombe, T. Veerati, F. Moheimani, S. Y. Wu, A. K. Sood, and S. Hua, Advances and challenges of liposome assisted drug delivery,, R. Mendez and S. Banerjee, Sonication-based basic protocol for liposome synthesis,, H. Zhang, Thin-film hydration followed by extrusion method for liposome preparation,, P. Guo, J. Huang, Y. Zhao, C. R. Martin, R. N. Zare, and M. A. Moses, Nanomaterial preparation by extrusion through nanoporous membranes,, C. Jaafar-Maalej, R. Diab, V. Andrieu, A. Elaissari, and H. Fessi, Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation,, M. Sala, K. Miladi, G. Agusti, A. Elaissari, and H. Fessi, Preparation of liposomes: a comparative study between the double solvent displacement and the conventional ethanol injection-From laboratory scale to large scale,, R. Schubert, Liposome preparation by detergent removal,, M. Gaumet, A. Vargas, R. Gurny, and F. Delie, Nanoparticles for drug delivery: the need for precision in reporting particle size parameters,, A. S. Hoffman, The origins and evolution of controlled drug delivery systems,, W. Lee, S. Sarkar, H. Ahn et al., PEGylated liposome encapsulating nido-carborane showed significant tumor suppression in boron neutron capture therapy (BNCT),, T. Asai and N. Oku, Angiogenic vessel-targeting DDS by liposomalized oligopeptides,, A. Gabizon, D. Tzemach, J. Gorin et al., Improved therapeutic activity of folate-targeted liposomal doxorubicin in folate receptor-expressing tumor models,, A. Garg, A. W. Tisdale, E. Haidari, and E. Kokkoli, Targeting colon cancer cells using PEGylated liposomes modified with a fibronectin-mimetic peptide,, K. R. Vega-Villa, J. K. Takemoto, J. In order to further minimize off-target side effects, different strategies have been employed to design actively targeted liposomes [27]. Passive loading refers to the direct encapsulation of lipophilic drugs into liposomes during vesicle formation [18]. demonstrated that indium 111-labelled liposomes could accumulate within solid tumours such as malignant lymphoma and Kaposis sarcoma [25]. These challenges include the mononuclear-phagocyte system (MPS) and the surrounding hypoxic environment [9]. pH-sensitive liposomes formulated with lipid palmitoyl homocysteine can enhance drug release in local triggers such as primary tumour regions with a mildly acidic pH [25]. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. One example of the most widely utilized polymers is polyethylene glycol (PEG); liposomes functionalized with this hydrophilic polymer are referred to as stealth liposomes as they sterically stabilize the liposome, decreasing particle aggregation and recognition by opsonins [7]. Reduced liposomal uptake into the liver and prolonged circulation half-lives were achieved with the replacement of sphingomyelin with egg phosphatidylcholine. The boronated liposomes exhibited profound tumour tissue penetration and demonstrated localization within the tumour cell cytoplasm. Furthermore, the liposomes modified with R8 delivered more doxorubicin to the site of action which culminated in increased in vitro apoptosis of cancer cells, tumour growth suppression, and enhanced cytotoxicity in mice[55]. Novel coupling strategies have been developed that involve the attachment of ligands to the terminus of PEG molecules on the surface of liposomes which resulted in enhanced in vivo mice lung tumour cell survival in comparison to nontargeted liposomal drugs [25]. Moderate improvements were observed in circulation half-lives when liposomal vesicle sizes were reduced during initial approaches. For the purpose of this review, passive loading techniques shall be discussed, these are subdivided into mechanical dispersion methods, solvent dispersion methods, and detergent removal methods. Consequently, ideal targeting can be obtained if liposomes are prepared with a size range appropriate for extravasation into tumour tissues and not normal tissues. However, the aforementioned preparation methods employ the use of toxic solvents including ethanol, ether solution, methanol, chloroform, and detergents to enhance the solubility of hydrophilic and hydrophobic ingredients [35, 36]. Solid tumours have both physiological and biological factors that demand the formulation of an effective drug delivery system. Furthermore, the deaths caused by cancer are projected to increase with 12 million deaths estimated to occur in 2030. A. Yez, C. M. Remsberg, M. L. Forrest, and N. M. Davies, Clinical toxicities of nanocarrier systems,, Z. Yang, B. C. K. Wong, H. Zhang et al., Carbonic anhydrase IX-directed immunoliposomes for targeted drug delivery to human lung cancer cells in vitro,, J. W. Park, K. Hong, D. B. Kirpotin et al., Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery,, A. Wicki, C. Rochlitz, A. Orleth et al., Targeting tumor-associated endothelial cells: anti-VEGFR2 immunoliposomes mediate tumor vessel disruption and inhibit tumor growth,, Y. K. Lee, T. S. Lee, I. H. Song et al., Inhibition of pulmonary cancer progression by epidermal growth factor receptor-targeted transfection with Bcl-2 and survivin siRNAs,, S. Biswas, N. S. Dodwadkar, P. P. Deshpande, S. Parab, and V. P. Torchilin, Surface functionalization of doxorubicin-loaded liposomes with octa-arginine for enhanced anticancer activity,, S. Moosavian, K. Abnous, A. Badiee, and M. Jaafari, Improvement in the drug delivery and anti-tumor efficacy of PEGylated liposomal doxorubicin by targeting RNA aptamers in mice bearing breast tumor model,, H. Maeda, H. Nakamura, and J. Fang, The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo,, V. P. Torchilin, Passive and active drug targeting: drug delivery to tumors as an example,, V. P. Torchilin, Targeted pharmaceutical nanocarriers for cancer therapy and imaging,, J. D. Byrne, T. Betancourt, and L. Brannon-Peppas, Active targeting schemes for nanoparticle systems in cancer therapeutics,, S. P. Egusquiaguirre, M. Igartua, R. M. Hernndez, and J. L. Pedraz, Nanoparticle delivery systems for cancer therapy: advances in clinical and preclinical research,, P. S. Low, W. A. Henne, and D. D. Doorneweerd, Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases,, R. Bharti, G. Dey, I. Banerjee et al., Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy,, J.-H. Park, H.-J.