Investigations about the feasibility of delivery systems with unmanned aerial vehicles (UAVs) or drones have been recently expanded, owing to the exponential demand for goods to be delivered in the recent years, which has been further increased by the COVID-19 pandemic. UAV delivery can provide new contactless delivery strategies, in addition to applications for medical items, such as blood, medicines, or vaccines. The safe delivery of goods is paramount for such applications, which is facilitated if the payload is embedded in the main drone body. In this paper, we investigate payload solutions for medium and small package delivery (up to 5 kg) with a medium-sized UAV (maximum takeoff of less than 25 kg), focusing on (i) embedded solutions (packaging hosted in the drone fuselage), (ii) compatibility with transportation of medical items, and (iii) user-oriented design (usability and safety). We evaluate the design process for possible payload solutions, from an analysis of the package design (material selection, shape definition, and product industrialization) to package integration with the drone fuselage (possible solutions and comparison of quick-release systems). We present a prototype for an industrialized package, a right prism with an octagonal section made of high-performance double-wall cardboard, and introduce a set of concepts for a quick-release system, which are compared with a set of six functional parameters (mass, realization, accessibility, locking, protection, and resistance). Further analyses are already ongoing, with the aim of integrating monitoring and control capabilities into the package design to assess the condition of the delivered goods during transportation.