Unilamellar vesicles or "liposomes" are commonly used as simple cell models and as drug delivery vehicles. A major limitation of unilamellar liposomes in these applications has been premature contents release in physiological environments. This premature release is likely due to enzyme degradation or protein insertion into the liposome membrane, which significantly increases the bilayer permeability. Encapsulating unilamellar liposomes within a second bilayer to form multicompartment "vesosomes" extends contents retention by 2 orders of magnitude by preventing enzymes and/or proteins from reaching the interior bilayers. The multicompartment structure of the vesosome can also allow for independent optimization of the interior compartments and exterior bilayer; however, just the bilayer-within-a-bilayer structure of the vesosome is sufficient to increase drug retention from minutes to hours. The vesosome is a better mimic of eukaryotic cell structure and demonstrates the benefits of multiple internal bilayer-enclosed compartments.