Click Reaction in the Synthesis of Dendrimer Drug-delivery Systems.
Current medicinal chemistry
Drug delivery systems are designed for the targeted delivery and controlled release of medicinal agents. Among the materials employed as drug delivery systems, dendrimers have gained increasing interest in recent years because of their properties and structural characteristics. The use of dendrimer-nanocarrier formulations enhances the safety and bioavailability, increases the solubility in water, improves stability and pharmacokinetic profile, and enables efficient delivery of the target drug to a specific site. However, the synthesis of dendritic architectures through convergent or divergent methods has drawbacks and limitations that disrupt aspects related to design and construction, and consequently, slow down the transfer from academia to industry. In that sense, the implementation of click chemistry has received increasing attention in the last years, as it offers new efficient approaches to obtain dendritic species in good yields and higher monodispersity. This review focuses on recent strategies for building dendrimer drug delivery systems using click reactions from 2015 to early 2021. The dendritic structures showed in this review are based on β -cyclodextrins (β-CD), poly(amidoamine) (PAMAM), dendritic poly (lysine) (PLLD), dimethylolpropionic acid (bis-MPA), phosphoramidate (PAD), and poly(propargyl alcohol-4-mercaptobutyric (PPMA).
Recent advances of dendrimer in targeted delivery of drugs and genes to stem cells as cellular vehicles.
Pishavar Elham,Oroojalian Fatemeh,Salmasi Zahra,Hashemi Ezzat,Hashemi Maryam
Stem cells can be used to repair dysfunctional and injured (or cancerous) tissues by delivering therapeutics. However, in comparison with other cells, it is harder to transfect drugs or genes into stem cells. Dendrimers have been considered as efficient vectors to deliver both genes and drugs to stem cells due to their unique properties including adjustable molecular weight and size, low toxicity, high loading capacity, and having multiple peripheral chemical agents which can be functionalized to improve deliverance efficiency. In this review, we discuss dendrimer-mediated drug and gene delivery to stem cells as cellular vehicles and the role of this strategy in treating a variety of disorders via regenerative medicine approaches.
Recent Advances in Preclinical Research Using PAMAM Dendrimers for Cancer Gene Therapy.
Tarach Piotr,Janaszewska Anna
International journal of molecular sciences
Carriers of genetic material are divided into vectors of viral and non-viral origin. Viral carriers are already successfully used in experimental gene therapies, but despite advantages such as their high transfection efficiency and the wide knowledge of their practical potential, the remaining disadvantages, namely, their low capacity and complex manufacturing process, based on biological systems, are major limitations prior to their broad implementation in the clinical setting. The application of non-viral carriers in gene therapy is one of the available approaches. Poly(amidoamine) (PAMAM) dendrimers are repetitively branched, three-dimensional molecules, made of amide and amine subunits, possessing unique physiochemical properties. Surface and internal modifications improve their physicochemical properties, enabling the increase in cellular specificity and transfection efficiency and a reduction in cytotoxicity toward healthy cells. During the last 10 years of research on PAMAM dendrimers, three modification strategies have commonly been used: (1) surface modification with functional groups; (2) hybrid vector formation; (3) creation of supramolecular self-assemblies. This review describes and summarizes recent studies exploring the development of PAMAM dendrimers in anticancer gene therapies, evaluating the advantages and disadvantages of the modification approaches and the nanomedicine regulatory issues preventing their translation into the clinical setting, and highlighting important areas for further development and possible steps that seem promising in terms of development of PAMAM as a carrier of genetic material.
Dendrimer-based drug delivery systems: history, challenges, and latest developments.
Journal of biological engineering
Since the first dendrimer was reported in 1978 by Fritz Vögtle, dendrimer research has grown exponentially, from synthesis to application in the past four decades. The distinct structure characteristics of dendrimers include nanoscopic size, multi-functionalized surface, high branching, cavernous interior, and so on, making dendrimers themselves ideal drug delivery vehicles. This mini review article provides a brief overview of dendrimer's history and properties and the latest developments of dendrimers as drug delivery systems. This review focuses on the latest progress in the applications of dendrimers as drug and gene carriers, including 1) active drug release strategies to dissociate drug/gene from dendrimer in response to stimuli; 2) size-adaptive and charge reversal dendrimer delivery systems that can better take advantage of the size and surface properties of dendrimer; 3) bulk and micro/nano dendrimer gel delivery systems. The recent advances in dendrimer formulations may lead to the generation of new drug and gene products and enable the development of novel combination therapies.
Surface decorations of poly(amidoamine) dendrimer by various pendant moieties for improved delivery of nucleic acid materials.
Dehshahri Ali,Sadeghpour Hossein
Colloids and surfaces. B, Biointerfaces
In recent years, the discovery of novel nucleic acid-based drug candidates (e.g., siRNA and miRNA) and the groundbreaking studies for somatic cell reprogramming into a state of pluripotency have led to reconsideration for the use of human gene therapy as a new paradigm with great therapeutic potential. However, the success of gene therapy is dependent on overcoming intra- and extracellular barriers hampering the efficient delivery of nucleic acid therapeutics into the target cells or tissues. Despite relatively low transfection efficiency, great attention has been directed to cationic polymers and dendrimers due to their ability to condense DNA and RNA molecules into nano-sized particles which is a necessary prerequisite for efficient transfer of nucleic acids into cells. These gene carriers show remarkable adaptability and significant capacity to transfer larger sizes of nucleic acid materials. Polyamidoamine (PAMAM) dendrimer has been employed as non-viral gene carrier due to its globular shape and well-defined structure containing abundant amino surface groups which provide possibility for surface decoration of the dendrimer via the conjugation of various moieties. In this review, we have brought out the various functionalization strategies of the PAMAM surface amines using different pendant moieties such as amino acids, proteins, cyclodextrins, and hydrophobic units in order to overcome intra- and extracellular barriers. These surface-decorated dendrimers possessing favorable properties provide substantial information and insight for redesigning existing dendrimers and polymers. By understanding the role played by the conjugated moieties, more efficient and novel designs of gene vehicles may be possible.
Recent Progress and Advances of Multi-Stimuli-Responsive Dendrimers in Drug Delivery for Cancer Treatment.
Le Ngoc Thuy Trang,Nguyen Thi Nhu Quynh,Cao Van Du,Hoang Duc Thuan,Ngo Van Cuong,Hoang Thi Thai Thanh
Despite the fact that nanocarriers as drug delivery systems overcome the limitation of chemotherapy, the leakage of encapsulated drugs during the delivery process to the target site can still cause toxic effects to healthy cells in other tissues and organs in the body. Controlling drug release at the target site, responding to stimuli that originated from internal changes within the body, as well as stimuli manipulated by external sources has recently received significant attention. Owning to the spherical shape and porous structure, dendrimer is utilized as a material for drug delivery. Moreover, the surface region of dendrimer has various moieties facilitating the surface functionalization to develop the desired material. Therefore, multi-stimuli-responsive dendrimers or 'smart' dendrimers that respond to more than two stimuli will be an inspired attempt to achieve the site-specific release and reduce as much as possible the side effects of the drug. The aim of this review was to delve much deeper into the recent progress of multi-stimuli-responsive dendrimers in the delivery of anticancer drugs in addition to the major potential challenges.