Dendrimer-based drug delivery systems: history, challenges, and latest developments

Wang, Juan; Li, Boxuan; Li, Qiu; Qiao, Xuguang; Yang, Hu

doi:10.1186/s13036-022-00298-5

Cited by 161 publications

(117 citation statements)

References 109 publications

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“…The use of a hydrophobic core enables noncovalent encapsulation of hydrophobic drugs, while surface functionalization enables targeting or multivalent display. Commonly used chemistries include poly(amidoamine) (PAMAM) [ 220 ], poly-2,2-bis(hydroxymethyl)propionic acid (bis-MPA) [ 221 ], and poly(L-lysine) dendrimers [ 222 ], but monodisperse, degradable PEG dendrimers have been recently reported as well [ 223 , 224 ]. Starpharma has several small molecule candidates in the clinic using their poly(L-lysine) dendrimer platform, but there are no protein or peptide dendrimer conjugates in the clinic to date.…”

Section: Protein/peptide Therapeutics That Are Enhanced Through Chemi...mentioning

confidence: 99%

A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future

Holz¹,

Darwish²,

Tesar³

et al. 2023

Pharmaceutics

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Over the past few decades, the complexity of molecular entities being advanced for therapeutic purposes has continued to evolve. A main propellent fueling innovation is the perpetual mandate within the pharmaceutical industry to meet the needs of novel disease areas and/or delivery challenges. As new mechanisms of action are uncovered, and as our understanding of existing mechanisms grows, the properties that are required and/or leveraged to enable therapeutic development continue to expand. One rapidly evolving area of interest is that of chemically enhanced peptide and protein therapeutics. While a variety of conjugate molecules such as antibody–drug conjugates, peptide/protein–PEG conjugates, and protein conjugate vaccines are already well established, others, such as antibody–oligonucleotide conjugates and peptide/protein conjugates using non-PEG polymers, are newer to clinical development. This review will evaluate the current development landscape of protein-based chemical conjugates with special attention to considerations such as modulation of pharmacokinetics, safety/tolerability, and entry into difficult to access targets, as well as bioavailability. Furthermore, for the purpose of this review, the types of molecules discussed are divided into two categories: (1) therapeutics that are enhanced by protein or peptide bioconjugation, and (2) protein and peptide therapeutics that require chemical modifications. Overall, the breadth of novel peptide- or protein-based therapeutics moving through the pipeline each year supports a path forward for the pursuit of even more complex therapeutic strategies.

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Section: Protein/peptide Therapeutics That Are Enhanced Through Chemi...mentioning

confidence: 99%

A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future

Holz¹,

Darwish²,

Tesar³

et al. 2023

Pharmaceutics

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“… Dendrimers were discovered later, at the end of the 1970s [ 64 ]. Their structure consists of a hydrophobic core, with chains of repeating units grafted onto it, branching off each other in a dendritic manner [ 65 ]. Functional groups can also be grafted at the periphery.…”

Section: Nanoparticlesmentioning

confidence: 99%

Nanosized Drug Delivery Systems to Fight Tuberculosis

2023

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Tuberculosis (TB) is currently the second deadliest infectious disease. Existing antitubercular therapies are long, complex, and have severe side effects that result in low patient compliance. In this context, nanosized drug delivery systems (DDSs) have the potential to optimize the treatment’s efficiency while reducing its toxicity. Hundreds of publications illustrate the growing interest in this field. In this review, the main challenges related to the use of drug nanocarriers to fight TB are overviewed. Relevant publications regarding DDSs for the treatment of TB are classified according to the encapsulated drugs, from first-line to second-line drugs. The physicochemical and biological properties of the investigated formulations are listed. DDSs could simultaneously (i) optimize the therapy’s antibacterial effects; (ii) reduce the doses; (iii) reduce the posology; (iv) diminish the toxicity; and as a global result, (v) mitigate the emergence of resistant strains. Moreover, we highlight that host-directed therapy using nanoparticles (NPs) is a recent promising trend. Although the research on nanosized DDSs for TB treatment is expanding, clinical applications have yet to be developed. Most studies are only dedicated to the development of new formulations, without the in vivo proof of concept. In the near future, it is expected that NPs prepared by “green” scalable methods, with intrinsic antibacterial properties and capable of co-encapsulating synergistic drugs, may find applications to fight TB.

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“…Among these, the family of dendritic polymers - highly branched macromolecules with nanosized dimensions consisting of repeating units and a large number of terminal functional groups - is one of the most studied categories of drug delivery systems ( Kurniasih et al., 2015 ; Paleos et al., 2016 ; Paleos et al., 2017 ; Sideratou et al., 2018 ; Cook and Perrier, 2019 ; Wang et al., 2022 ). Due to their three-dimensional architecture, nanocavities can efficiently encapsulate various bioactive compounds such as anticancer drugs, antibiotic drugs, etc.…”

Section: Introductionmentioning

confidence: 99%

Vancomycin-nanofunctionalized peptide-enriched silk fibroin to prevent methicillin-resistant Staphylococcus epidermidis-induced femoral nonunions in rats

Bottagisio

Palombella²,

Lopa³

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionImplant-related infections and infected fractures are significant burdens in orthopedics. Staphylococcus epidermidis is one of the main causes of bone infections related to biofilm formation upon implants. Current antibiotic prophylaxis/therapy is often inadequate to prevent biofilm formation and results in antibiotic resistance. The development of bioactive materials combining antimicrobial and osteoconductive properties offers great potential for the eradication of microorganisms and for the enhancement of bone deposition in the presence of infections. The purpose of this study is to prevent the development of methicillin-resistant S. epidermidis (MRSE)-infected nonunion in a rat model.MethodsTo this end, a recently developed in our laboratories bioactive material consisting of antibiotic-loaded nanoparticles based on carboxylic acid functionalized hyperbranched aliphatic polyester (CHAP) that are integrated into peptide-enriched silk fibroin sponges with osteoconductive properties (AFN-PSF) was employed, whose biocompatibility and microbiological tests provided proof of its potential for the treatment of both orthopedic and dental infections. In particular, non-critical femoral fractures fixed with plates and screws were performed in Wistar rats, which were then randomly divided into three groups: 1) the sham control (no infection, no treatment); 2) the control group, infected with MRSE and treated with peptide-enriched silk fibroin sponges incorporating non-drug-loaded functionalized nanoparticles (PSF); 3) the treated group, infected with MRSE and treated with peptide-enriched silk fibroin sponges incorporating vancomycin-loaded functionalized nanoparticles (AFN-PSF). After 8 weeks, bone healing and osteomyelitis were clinically assessed and evaluated by micro-CT, microbiological and histological analyses.ResultsThe sham group showed no signs of infection and complete bone healing. The PSF group failed to repair the infected fracture, displaying 75% of altered bone healing and severe signs of osteomyelitis. The AFN-PSF treated group reached 70% of fracture healing in the absence of signs of osteomyelitis, such as abscesses in the cortical and intraosseous compartments and bone necrosis with sequestra.DiscussionAFN-PSF sponges have proven effective in preventing the development of infected nonunion in vivo. The proposed nanotechnology for local administration of antibiotics can have a significant impact on patient health in the case of orthopedic infections.

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Dendrimer-based drug delivery systems: history, challenges, and latest developments

Cited by 161 publications

References 109 publications

A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future

A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future

Nanosized Drug Delivery Systems to Fight Tuberculosis

Vancomycin-nanofunctionalized peptide-enriched silk fibroin to prevent methicillin-resistant Staphylococcus epidermidis-induced femoral nonunions in rats

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