# An Overview of Biopolymers for Drug Delivery Applications
## 5 Mechanisms Involved in Drug Delivery Systems  
Innovative drug delivery systems are widely studied nowadays due to the increasing demands on their quality [171]. DDSs are preferred due to reasons such as the fact that drugs can be administered in their active form or, on the other end, can be stabilized by the functionalization of the carrier. Moreover, the presence of a DDS ensures administration through body cavities that in other ways could be impractical. Therefore, these qualities lead these systems to be characterized by low costs, higher efficiency, and better therapies [172]. Drugs can be administrated using different systems depending on the necessities of the patient. The most common are the ones that ensure an immediate release or a controlled and prolonged release. An immediate release is accomplished through pills, capsules, and injections, and even though they have very important clinical applications, they do not have a good pharmacokinetic profile, meaning they cannot be used for different therapies [173]. A prolonged release is obtained using implantable devices that can allow the drug to be released over weeks, months, or even years. The most common applications are in contraception and cancer therapies. However, the installed devices are mostly made of non-biodegradable polymers, meaning that, after the end of the therapy, they need to be surgically removed [174]. The controlled release systems made of biopolymers or other biomolecules are preferred to the others due to their advantages compared to conventional ones, such as improved efficacy, improved patient compliance, and reduced toxicity [175; 176]. The first parameters to study in order to develop a highly efficient drug delivery system are the parameters that characterize the drug, such as its physicochemical properties, pharmacokinetics, and pharmacodynamics [177]. The study of the physicochemical properties of the drug is crucial for the optimization of the delivery system; some of the key properties are, for example, drug solubility, molecular weight, chemical stability, and surface tension. For instance, the diffusivity of a drug is strictly dependent on its molecular weight; thus, the carrier chosen for a small molecule and a polypeptide should differ to enhance the delivery capacity [178]. Once these parameters are studied, the right carrier must be found, and the drug must be loaded. One of the most crucial aspects of the system is drug loading, which is the process of integrating the medication into the carrier. The ideal loading strategies for the introduction have to be determined through a study of the compatibility between the elements that characterize the entire system (drug, carrier, and excipients), but release environment should be also taken into account for a better experiment yield. Therapeutics can be introduced by both covalent and non-covalent interactions, such as ionic interactions, dipole interactions, hydrogen bonding, etc., but also via physical encapsulation and surface absorption [179]. Covalent bond-based systems, which are used, for example, in small drug-drug complexes, linear polymer prodrugs, and dendritic drugs, are mostly used when the drug's solubility and biocompatibility need to be improved. These properties are achieved by linking hydrophobic or hydrophilic segments, forming an amphiphilic structure. Not all covalent bonds can be used for this strategy because, to ensure the release, these bonds must be susceptible to enzymes, pH, T, or other possible external stimulations [180]. Non-covalent systems are valid alternatives to covalent ones due to qualities such as their reversibility, biocompatibility, bioactivity, and their natural responsive behavior to stimuli, allowing the system to be adaptable to any changes in physiological conditions, offering targeted and stimuli-responsive release. Examples of these systems are micelles and dendrimers.