Over the last few decades, the field of polymer therapeutics has been revolutionized and the immense potential of polymer drugs in the field of drug delivery systems is attracting the scientific community around the globe. Hurdles like poor pharmacokinetics and toxic profile can be easily overcome by the use of drug–polymer bioconjugates. Ester and ortho-ester linkage are widely utilized in the conjugation as ester linkages are easily hydrolyzed by the esterase enzyme at the physiological pH making them an attractive target for conjugation between drug and polymer. In this chapter, the bioconjugates tailored by the ester and ortho-ester linkers are explored and discussed. It covers the understanding of the tailoring mechanism of conjugate formation, hydrolysis of ester bond, and ortho-ester bond along with an elaborated data collection of its applications so that it can help the scientific fraternity to understand the etiology of these bioconjugates as potential chemotherapeutic agents.

Dendrimers have been emerged as a potential carrier for therapeutic agents due to the unique properties they possess, i.e., well-defined structure, monodispersity, and pliability for surface functionalization with ligands or therapeutic molecule. Dendrimers have been explored as scaffold for delivery of therapeutic agents. The presence of functional surface groups over periphery of dendrimers has been employed for conjugating the therapeutic entities through covalent bonding to improve drug release kinetics via stimuli-responsive, controlled, and targeted release of attached therapeutic moieties. The stimuli-responsive functionality allows the release of drug in response to the specific trigger (acid, redox potentials, or enzyme) at the targeted site. For the development of dendrimer–drug conjugates (DDCs), linker chemistry plays an important role in determining the optimal drug delivery at the targeted sites by conserving efficacy of therapeutic agent and influencing desired drug release pattern. DDCs have emerged as a promising delivery system with improved drug stability during systemic circulation, better pharmacokinetic profile, and targeted drug delivery. The DDCs have received a considerable attention for the delivery of various therapeutic agents including anticancer, antiinflammatory, and antimicrobial drugs. This chapter discusses the functionalization of dendrimers with drug either directly or via different linkers and highlights the significance of chemical nature of bonds for the controlled release of the free drug at the targeted site.

Poor pharmacokinetic and biopharmaceutical properties are the biggest challenges for newly discovered chemical entities as well as for existing therapeutic molecules. Although conventional formulation development remains a primary strategy for pharmaceutical industries due to its ease of manufacturing. However, these are associated with active pharmaceutical ingredient (API) access to nontargeted tissue/cells, metabolic inactivation, reticuloendothelial system (RES) uptake, low permeability, and bioavailability leading to lower therapeutic efficacy with increased chances of toxicity. In order to counteract such complications related to APIs, there is an urgent need to develop an appropriate drug delivery system that dispenses therapeutic molecules into a specific tissue or organ without any interactions with normal tissue or organs. Targeting is generally achieved via active or passive mechanisms. In passive targeting, the carrier system prolongs residence time and leads to higher bioavailability, whereas active targeting involves the selective binding of drug molecules to receptors of the targeted sites. The targeted drug delivery system is mostly applied for the treatment of cancer, parasite, neurodegenerative, cardiovascular, or infectious diseases. This chapter primarily emphasizes the mechanism and significance of active or passive targeting approaches in drug delivery with their salient features and fundamentals through different routes of administration.

By increasing the number of drug molecules while decreasing systemic drug exposure, targeted drug delivery seeks to improve the therapeutic efficacy. Since the 1990s, a number of polymeric–drug and polymer–protein conjugates have been available on the market. However, while being in clinical trials currently, polymer–drug conjugates still need to achieve this ultimate objective. A stronger understanding of cell biology, together with the tremendous advancements in polymer chemistry and bioconjugation strategies, has created an array of new, fascinating problems and opportunities. This book chapter highlights drug–polymer conjugation, tracing its development and outlining its potential. The “technology platform” of polymer therapeutics enables the creation of unique and intriguing polymeric materials as well as their combination with novel bioactive agents to meet current advancements in drug therapy.

The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer–drug conjugates with a wide variety of architectures and chemical properties. Various polymers which act as a carrier such as hydroxy propyl methacrylamide/methacrylic acid, polyethylene glycol, poly (organo) phosphazenes, poly (l-glutamic) acid, poly (ortho) esters, polyphosphoesters and polyurethanes have been translated to use in the clinical practice. These functionalized polymer–drug conjugates are increasingly being utilized to obtain stimuli-responsive and targeted systems in an attempt to enhance the localized delivery of the drug. In this chapter, various copolymers used for preparing the polymer–drug conjugates and their therapeutic applications have been discussed. In addition, various types of linkages involved in the polymer–drug conjugate, followed by a review of the chemistry behind the conjugation of polymer–drug and its implication in the drug delivery, have also been summarized in this chapter.

Polymer science has enriched the domain and practice of modified/controlled drug delivery systems over the last decade. The newer and novel polymeric systems are catering the ever-changing canvass of drug delivery system. Polymers have shown a great promise in the field of drug delivery technology. Some of the recently developed novel polymeric systems have inherent properties of sustained and controlled release profile of medicinal substances over a longer period of time, localized therapeutic effect, and a synchronized release pattern of both hydrophilic and lipophilic drugs. The novel polymeric systems have opened newer frontiers in various disease therapies. It has turned out to be a multidisciplinary science where a well-coordinated knowledge of biology, chemistry, and engineering is required. With the advent of various synthetic polymers having self-tunable and assembly properties, it has revolutionized the drug delivery systems and dosage form design. The recently developed polymers have not only the unique ability of intracellular delivery of therapeutics but also have stimuli-responsive property, gene delivery ability, and biomimicking ability. This chapter encompasses some of the recently developed polymer-linker systems as well as their structural and functional consideration in nitty-gritty details.

In this chapter, the author focuses on the drug–polymer conjugate tailoring by a disulfide linkage. This involves using a medicine conjugate that takes advantage of the fact that this unique covalent bond can be broken and put back together again. This method was just recently approved for human use. Many studies have concluded that disulfide linkages are now used to connect drug polymers for drug delivery in the next generation of pharmaceuticals. This chapter also covered how the problems with some cancer or virus treatments, such as nonselective cytotoxicity and short half-lives, have been fixed. All of these problems can be fixed by tailoring the drug–polymer conjugate with a disulfide linkage. This chapter also explains how and where tailoring by disulfide bonds in drug polymers affects the design of the delivery and how the delivery strategies are interpreted. In some sections of the chapter, we talked briefly about a few promising disulfide-containing prodrugs and brought up some major problems with studying and making disulfide-containing prodrugs: that the release of the active ingredient only happens in tumors, which factors affect how disulfide bonds burn in living things? And What problems do disulfide-containing prodrugs face now and, in the future, when they go from the lab to the clinic? This chapter concluded with the applications of drug-polymer conjugates in drug delivery.

The amide group is referred to as a peptide bond when it is found in the main chain of a protein, and an amide bond (isopeptide) bond when it is located in the side chain of a protein, as in the amino acids asparagine and glutamine. The amide bond is the most fundamental functional group in many areas of chemistry, pharmacy, and bioengineering, such as chemical synthesis, drug discovery, polymers, and biochemistry. The amide functional group is important in the composition of biomolecules, including several therapeutically approved drugs. Bioisosterism is frequently employed in the rational modification of lead compounds to improve potency, selectivity, pharmacokinetic characteristics, reduce toxicity, and protect intellectual property by obtaining novel chemical space. The most common covalent connections for conjugating drugs to superparamagnetic iron oxide nanoparticles are amide bonds, which are created by reacting the drug with an amine. The reaction of an amine group with an N-hydroxysuccinimide (NHS)–activated carboxylic molecule to form an amide bond is a favored direct conjugation approach. By reacting a carboxylic molecule with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and NHS, a carboxylic molecule becomes an acyl amino ester.

Targeted and controlled drug delivery systems are widely utilized nowadays to deliver drugs for the treatment of various diseases. A targeted drug delivery system in biomedicals essentially deals with polymer–drug conjugates (PDCs), which have superior effects in terms of bioavailability, reduced toxicity, and biocompatibility, when compared to traditional drug delivery systems. The most important component in the production of the PDC is a linker, which is responsible for joining two molecules and releasing the active molecule at the target location in response to external and internal stimuli. This chapter discusses the rational design of linkers in PDCs, followed by a study of the various classes of linkers involved in polymer conjugates.

Carbamates or carbamate linkage owns a significant place in pharmaceutical field due to their wide range of applications viz. intermediate or linkers in various organic reactions, in improving pharmacokinetic as well as pharmacodynamic profile of the compounds, in designing of prodrugs, herbicides, etc. Being highly stable and potent with good drug interactions, incorporation of carbamate linkage is highly preferable these days to modulate the existing drugs as well as designing of new drug molecules with better efficacy, stability, and physicochemical properties. Carbamate–drug conjugates have extensive applications in cancer therapy, in diabetes, in asthma, in CNS disorders, in angina, inflammation, etc. Therefore, this chapter is designed to highlight the applications of carbamates in drug delivery with brief insight of their mode of action and structural considerations.