Levels of Drug Targeting

Yadav, Khushwant S.; Mishra, Dinesh Kumar; Deshpande, Ashwini; Pethe, Anil M.

doi:10.1016/b978-0-12-817909-3.00007-8

Cited by 22 publications

(11 citation statements)

References 101 publications

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“…Nanocarriers have the capacity to increase the concentration of the drug without causing drug toxicity. The supply of the drug to the specified compartments of the tissues within the cells is called cellular and intracellular targets [ 73 ]. Nanocarriers are used to deliver the drug to the sites where drug penetration is difficult due to the anatomical barriers.…”

Section: Nanocarriers In Controlled and Targeted Drug Deliverymentioning

confidence: 99%

“…In the active mode, the specific marker, which is expressed exclusively in the diseased cells but not in the normal cells, is targeted [ 75 ]. This targeting can be accomplished by allowing a molecule to bind with folate receptors that are over-expressed in the diseased cells [ 73 ]. For instance, CA-125 is one of the biomarkers that is overexpressed in ovarian cancer and can be targeted for active targeting mechanisms.…”

Section: Nanocarriers In Controlled and Targeted Drug Deliverymentioning

confidence: 99%

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Controlled Drug Delivery Systems: Current Status and Future Directions

2021

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The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma drug level and are unable to achieve sustained release. Without an efficient delivery mechanism, the whole therapeutic process can be rendered useless. Moreover, the drug has to be delivered at a specified controlled rate and at the target site as precisely as possible to achieve maximum efficacy and safety. Controlled drug delivery systems are developed to combat the problems associated with conventional drug delivery. There has been a tremendous evolution in controlled drug delivery systems from the past two decades ranging from macro scale and nano scale to intelligent targeted delivery. The initial part of this review provides a basic understanding of drug delivery systems with an emphasis on the pharmacokinetics of the drug. It also discusses the conventional drug delivery systems and their limitations. Further, controlled drug delivery systems are discussed in detail with the design considerations, classifications and drawings. In addition, nano-drug delivery, targeted and smart drug delivery using stimuli-responsive and intelligent biomaterials is discussed with recent key findings. The paper concludes with the challenges faced and future directions in controlled drug delivery.

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Section: Nanocarriers In Controlled and Targeted Drug Deliverymentioning

confidence: 99%

Section: Nanocarriers In Controlled and Targeted Drug Deliverymentioning

confidence: 99%

Controlled Drug Delivery Systems: Current Status and Future Directions

2021

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“…Despite ongoing nanomedicine research based on nano-based drug delivery systems (DDSs), the journey to clinical approval is arduous . Challenging obstacles such as the ease of preparation, safety, and cost of the materials, scalability, batch-to-batch reproducibility, and the stability, biocompatibility, and biodegradation of the final product need to be considered. − Since Doxil, the first FDA-approved nanodrug, several formulations for passive and active targeting can be found in the market . These DDSs produce biologically reproducible activities but lack precise control over the type, number, and location of the biologically relevant cargo within the carrier.…”

Section: Introductionmentioning

confidence: 99%

“…6−8 Since Doxil, the first FDA-approved nanodrug, several formulations for passive and active targeting can be found in the market. 9 These DDSs produce biologically reproducible activities but lack precise control over the type, number, and location of the biologically relevant cargo within the carrier. This would provide critical information about the therapeutic response of such materials and enable personalized treatment.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Heterofunctional Polyester Dendrimers with Internal and External Functionalities as Versatile Multipurpose Platforms

et al. 2020

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Heterofunctional dendrimers with internal and external representations of functionalities are considered as the ultimate dendritic frameworks. This is reflected by their unprecedented scaffolding, such as precise control over the structure, molecular weight, number, and location of different cargos across the whole dendritic skeleton. Consequently, these dendrimers with multipurpose characters are the pinnacle of precision polymers and thereof are highly attractive to the scientific community as they can find use in a great number of cutting-edge applications, especially as discrete unimolecular carriers for therapeutic exploitation. Unfortunately, most established dendrimer families display external functionalities but lack internal scaffolding ability, which leads to inherent limitations to their full potential use as precision carriers. Consequently, here, we embark on a novel synthetic strategy facilitating the introduction of internal functionalization of established dendrimers. As a proof of concept, a new class of internally and externally functionalized multipurpose dendrimers based on the established 2,2-bis(methylol)propionic acid (bis-MPA) was successfully obtained by the elegant and simple design of AB2C monomers, amalgamated from two traditional AB2 monomers. Utilizing fluoride-promoted esterification (FPE), straightforward layer-by-layer divergent growth up to the fourth generation was successful in less than one day of reaction time, with a molecular weight of 15 kDa, and displaying 93 reactive groups divided by 45 internal and 48 external functionalities. The feasibility of postfunctionalization through click reactions is demonstrated, where the fast and effective attachment of drugs, dyes, and PEG chains is achieved, as well as cross-linking into multifunctional hydrogels. The simplicity and versatility of the presented strategy can easily be transferred to generate a myriad of functional materials such as polymers, surfaces, nanoparticles, or biomolecules.

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“…For the active targeting, there has to be appropriate receptor inside the body. Substantial presence of such receptors, that is, higher expression, is mandatory for good targeting ability (Soni & Yadav, 2015; Yadav et al, 2011; Yadav, Mishra, Deshpande, & Pethe, 2019). The folate receptor (FR), overexpressed in many types of cancers, is one of the most commonly known biomarkers amenable for targeted delivery (Farran et al, 2019; Ledermann, Canevari, & Thigpen, 2015).…”

Section: Introductionmentioning

confidence: 99%

An outlook on procedures of conjugating folate to (co)polymers and drugs for effective cancer targeting

Kharkar

Soni

Rathod

et al. 2020

Drug Development Research

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Folate receptors (FRs) are expressed in vast majority of cancers. Selective targeting of the FRs is, therefore, one of the most popular and sought‐after strategies for improving the efficacy of cancer therapeutics. Variety of approaches involving folate conjugation to several well‐known and novel, nontoxic, biodegradable, and biocompatible (co)polymers have been attempted and successfully applied to a large number of nanoparticulate drug delivery systems (micelles, liposomes, nanoparticles, quantum dots, mesoporous silica‐based materials, and others) in the last decade‐and‐a‐half. Standard and novel synthetic approaches were utilized for the conjugation, followed by the formulation of the drug delivery modality. In most of the cases, the targeted system lived up to its reputation, validating its usefulness in targeted cancer therapeutics. The present review summarizes the progress and state‐of‐the‐art synthetic methodologies for folate conjugation to (co)polymers, drugs, and nucleic acids. The limitations of the FR targeting are discussed in brief to give the reader the other side of the story. Finally, the information on marketed folic acid conjugates highlight their industrial applications.

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Levels of Drug Targeting

Cited by 22 publications

References 101 publications

Controlled Drug Delivery Systems: Current Status and Future Directions

Controlled Drug Delivery Systems: Current Status and Future Directions

Synthesis of Heterofunctional Polyester Dendrimers with Internal and External Functionalities as Versatile Multipurpose Platforms

An outlook on procedures of conjugating folate to (co)polymers and drugs for effective cancer targeting

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