Fatty Acid Esters of G<sub>0</sub>-(Propyl Ether Imine) Dendron as Bicephalous Heterolipids for Permeation Enhancement in Transdermal Drug Delivery

Chaudhari, Kapil S.; Akamanchi, Krishnacharya G.

doi:10.1021/acsbiomaterials.8b00953

Cited by 6 publications

(3 citation statements)

References 54 publications

(181 reference statements)

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“…56 Similar transdermal carriers have been reported with inward-directed PAMAM dendrons with poly(lauryl methacrylate) on the branch ends 82 and with poly(propyl ether imine) dendron− lipid micelles. 83 A high density of functional groups on the hydrophilic shell of a micelle can also be leveraged for targeting. Ultimately, targeted nanomedicines enhance the tissue-specific delivery, opening the door to higher doses with few side effects.…”

Section: ■ Dendron Micelles In Cancer Drug Loading Transport Targetin...mentioning

confidence: 99%

“…Yang et al used PCL-G3 PAMAM dendron–PEG micelles to encapsulate the estrogen receptor modulator endoxifen for topical delivery to breast tumors . Similar transdermal carriers have been reported with inward-directed PAMAM dendrons with poly(lauryl methacrylate) on the branch ends and with poly(propyl ether imine) dendron–lipid micelles …”

Section: Dendron Micelles In Cancer Drug Loading Transport Targeting ...mentioning

confidence: 99%

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Dendritic–Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery

et al. 2022

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Polymers constitute a diverse class of macromolecules that have demonstrated their unique advantages to be utilized for drug or gene delivery applications. In particular, polymers with a highly ordered, hyperbranched structure“dendrons”offer significant benefits to the design of such nanomedicines. The incorporation of dendrons into block copolymer micelles can endow various unique properties that are not typically observed from linear polymer counterparts. Specifically, the dendritic structure induces the conical shape of unimers that form micelles, thereby improving the thermodynamic stability and achieving a low critical micelle concentration (CMC). Furthermore, through a high density of highly ordered functional groups, dendrons can enhance gene complexation, drug loading, and stimuli-responsive behavior. In addition, outward-branching dendrons can support a high density of nonfouling polymers, such as poly(ethylene glycol), for serum stability and variable densities of multifunctional groups for multivalent cellular targeting and interactions. In this paper, we review the design considerations for dendron–lipid nanoparticles and dendron micelles formed from amphiphilic block copolymers intended for gene transfection and cancer drug delivery applications. These technologies are early in preclinical development and, as with other nanomedicines, face many obstacles on the way to clinical adoption. Nevertheless, the utility of dendron micelles for drug delivery remains relatively underexplored, and we believe there are significant and dramatic advancements to be made in tumor targeting with these platforms.

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Section: ■ Dendron Micelles In Cancer Drug Loading Transport Targetin...mentioning

confidence: 99%

Section: Dendron Micelles In Cancer Drug Loading Transport Targeting ...mentioning

confidence: 99%

Dendritic–Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery

et al. 2022

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“…Our group has been involved in designing and developing new amine-containing heterolipid-based carriers for delivery of therapeutic molecules. − In the present work, by employing a data set from the literature, a quantitative structure–activity relationship (QSAR) model has been developed using a partial least-squares regression (PLSR) technique for prediction of surface p K a . The developed model has been further validated by synthesizing selected newly designed heterolipids and comparing their predicted versus experimentally determined p K a values.…”

Section: Introductionmentioning

confidence: 99%

Experimentally Validated QSAR Model for Surface pK_a Prediction of Heterolipids Having Potential as Delivery Materials for Nucleic Acid Therapeutics

et al. 2020

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The application of lipid-based drug delivery technologies for bioavailability enhancement of drugs has led to many successful products in the market for clinical use. Recent studies on amine-containing heterolipid-based synthetic vectors for delivery of siRNA have witnessed the United States Food and Drug Administration (USFDA) approval of the first siRNA drug in the year 2018. The studies on various synthetic lipids investigated for delivery of such nucleic acid therapeutics have revealed that the surface pK a of the constructed nanoparticles plays an important role. The nanoparticles showing pK a values within the range of 6−7 have performed very well. The development of high-performing lipid vectors with structural diversity and falling within the desired surface pK a is by no means trivial and requires tedious trial and error efforts; therefore, a practical solution is called for. Herein, an attempt to is made provide a solution by predicting the statistically significant pK a through a predictive quantitative structure−activity relationship (QSAR) model. The QSAR model has been constructed using a series of 56 amine-containing heterolipids having measured pK a values as a data set and employing a partial least-squares regression coupled with stepwise (SW-PLSR) forward algorithm technique. The model was tested using statistical parameters such as r 2 , q 2 , and pred_r 2 , and the model equation explains 97.2% (r 2 = 0.972) of the total variance in the training set and it has an internal (q 2 ) and an external (pred_r 2 ) predictive ability of ∼83 and ∼63%, respectively. The model was validated by synthesizing a series of designed heterolipids and comparing measured surface pK a values of their nanoparticle assembly using a 2-(p-toluidino)-6-napthalenesulfonic acid (TNS) assay. Predicted and measured surface pK a values of the synthesized heterolipids were in good agreement with a correlation coefficient of 93.3%, demonstrating the effectiveness of this QSAR model. Therefore, we foresee that our developed model would be useful as a tool to cut short tedious trial and error processes in designing new amine-containing heterolipid vectors for delivery of nucleic acid therapeutics, especially siRNA.

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Micro‐ and Nanosystems for Advanced Transdermal Delivery

Alba

Tabassum

et al. 2019

Advanced Therapeutics

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The skin is the largest and most accessible organ in the human body and, as such, it appears as the most convenient portal for drug delivery. However, the skin is also a formidable barrier which, while protecting us from physical, chemical, and immunological agents, requires appropriate technology for effective delivery. Today, the most effective administration method for large, lipophobic, and polar molecules continues to be hypodermic injection, which is associated with pain, needle phobia, and stick injury. As an alternative, a range of advanced strategies to overcome the skin barrier have been established over the last few decades including chemical enhancement, sonophoresis, iontophoresis, electroporation, thermal ablation, and mechanical approaches. Encouraged by the advances in nanotechnology, micro-and nanosystems have emerged as powerful tools to overcome the skin barrier, enabling significant advances on the existing methods. In particular, microneedle-and nanoparticle-assisted transdermal delivery has gained significant traction and will most likely have a strong impact in the field. In this review, the most recent progress in the field of transdermal delivery based on microneedle and nanoparticle delivery systems is discussed and examples of key therapeutic application are provided. Finally, a critical summary is presented alongside a vision for future research directions.

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Fatty Acid Esters of G₀-(Propyl Ether Imine) Dendron as Bicephalous Heterolipids for Permeation Enhancement in Transdermal Drug Delivery

Cited by 6 publications

References 54 publications

Dendritic–Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery

Dendritic–Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery

Experimentally Validated QSAR Model for Surface pK_a Prediction of Heterolipids Having Potential as Delivery Materials for Nucleic Acid Therapeutics

Micro‐ and Nanosystems for Advanced Transdermal Delivery

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Fatty Acid Esters of G0-(Propyl Ether Imine) Dendron as Bicephalous Heterolipids for Permeation Enhancement in Transdermal Drug Delivery

Cited by 6 publications

References 54 publications

Dendritic–Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery

Dendritic–Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery

Experimentally Validated QSAR Model for Surface pKa Prediction of Heterolipids Having Potential as Delivery Materials for Nucleic Acid Therapeutics

Micro‐ and Nanosystems for Advanced Transdermal Delivery

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Product

Resources

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Fatty Acid Esters of G₀-(Propyl Ether Imine) Dendron as Bicephalous Heterolipids for Permeation Enhancement in Transdermal Drug Delivery

Experimentally Validated QSAR Model for Surface pK_a Prediction of Heterolipids Having Potential as Delivery Materials for Nucleic Acid Therapeutics