## 3 In Vivo Applications of MIP-Based DDS  
MIPs are promising DDSs due to their ability to provide sustained or controlled release and targeted delivery of a selected drug, related to their high binding affinity to the template. To date, various MIP-DDS have been developed for oral, intravenous, ocular, or transdermal administration. They were effective in various pathologies, such as: cancer, arrhythmias, avitaminosis, cardiovascular and brain disease, inflammatory disorders and addiction therapy [1]. Using MIPs as controlled DDS has a number of advantages, such as the administration of lower drug doses due to the high drug loading or targeted delivery,thus reducing any useless spread in the body. This leads to fewer side effects, along with the possibility of attaining high concentrations of the drug in the targeted tissues [24]. Their advantages are illustrated in Figure 3.  
Oncology is one of the major fields in which functional polymers can bring significant benefits. The use of MIPs plays an important role in the efficacy of chemotherapy as it can assure a targeted and controlled delivery of antitumor agents. By incorporating chemotherapy agents into MIPs, their release kinetics is significantly improved [11]. There are three possible mechanisms of drug release from polymeric matrices: diffusion, erosion, and desorption of a surface-adsorbed drug. When the drug is homogenously dispersed in the matrix, release occurs due to diffusion, while erosion takes place when using a (bio)degradable matrix. An initial burst release of the drug occurs through a fast initial desorption process from MIP's surface [25]. Imprinted drug reservoirs can provide a sustained zero-order release, for a long period of time, while protecting the active ingredient from enzymatic, hydrolytic or photo-degradation, thus increasing its bioavailability [4]. Most conventional DDS show major limitations that negatively affect the activity of chemotherapeutic agents for various reasons, such as a decreased loading capacity or burst release of the embedded molecule [26]. MIPs, however, can be designed to release their payload as feed-back to external stimuli [5]. A smart MIP-based DDS can be fabricated using chemicals with magnetic properties, materials sensitive to pH, temperature, biological macromolecules or even UV light. Combining MIT and stimuli-responsiveness can improve the absorption and release profile through changes in the environment [1]. Variations in the pH is the most commonly used strategy for the development of MIP-DDS for cancer therapy. Acidic pH values in the tumor environment can be exploited to break the bonds in the DDS, finally leading to an increased drug release [11]. As highlighted by [PERSON] et. al. in their most recent review, MIPs have become promising platforms for both the in vitro and in vivo administration of therapeutical agents. They exceed the limitations of \"natural antibodies\" in terms of synthesis costs, immunogenicity and stability, thus being preferred for potential clinical applications [5]. From a fit-for-purpose perspective, MIPs employed in drug delivery applications can be broadly divided into two categories: MIP-based reservoirs and imprinted injectable nano-systems. Their critical characteristics are summarized and compared in Table 1. The first type of DDS is represented by the conventional bulk solid MIPs or hydrogels, or by the micron-sized imprinted particles that are not carried out by the vascular system. Whether  
Figure 3: Features of an ideal MIP as DDS. This illustration shows the most important features for MIPs as DDS, which include their biocompatibility, biodegradability, low immunogenicity, controlled release, high drug loading, target specificity and stimuli-responsiveness. external to the body or implanted, this type of DDS is generally intended to be administered once or sporadically in a specific region of the body, for a long-term local or systemic activity. High drug loading capacities are desirable, so that lower amounts of vehicles need to be implanted.