Lipid-based nanocarriers challenging the ocular biological barriers: Current paradigm and future perspectives

Abla, Kawthar K.; Mehanna, Mohammed M.

doi:10.1016/j.jconrel.2023.08.018

Cited by 5 publications

(3 citation statements)

References 197 publications

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“…White solid, yield 65%. 1 (14). 13 To a solution of 4,4′-(6-chloro-1,3,5-triazine-2,4-diyl)dimorpholine (13, 0.6 g, 2.1 mmol) in DME/H 2 O (5:1, 6.0 mL) were added 4aminophenylboronic acid pinacol ester (2.5 g, 2.4 mmol), K 2 CO 3 (0.72 g, 5.2 mmol), and Pd(PPh 3 ) 4 (0.12 g, 0.1 mmol).…”

Section: Synthesis Of Intermediates 7c−d and 8a−dmentioning

confidence: 99%

“…In addition, because of a variety of pharmaceutical benefits of lipid-based nanocarriers, including encapsulation of hydrophobic and hydrophilic chemical fractions, improved solubility and stability, better protection in biological environments, and site-specific delivery of chemotherapeutic agents, − lipid-based nanocarriers have been accepted as promising nanosystems for the delivery of candidates with poor drug-like properties. Herein, we further prepared lipodisc-based nanocarriers for efficient encapsulation and in vivo delivery of both PT-88 and PT-1 , and their in vivo pharmacokinetic profiles, biosafety, and antibreast cancer effects were systematically evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer

Sun,

Chu,

Zhang

et al. 2024

J. Med. Chem.

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The aberrant activation of the PI3K/mTOR signaling pathway is implicated in various human cancers. Thus, the development of inhibitors targeting mTOR has attracted considerable attention. In this study, we used a structure-based drug design strategy to discover a highly potent and kinaseselective mTOR inhibitor 24 (PT-88), which demonstrated an mTOR inhibitory IC 50 value of 1.2 nM without obvious inhibition against another 195 kinases from the kinase profiling screening. PT-88 displayed selective inhibition against MCF-7 cells (IC 50 : 0.74 μM) with high biosafety against normal cells, in which autophagy induced by mTOR inhibition was implicated. After successful encapsulation in a lipodisc formulation, PT-88 demonstrated favorable pharmacokinetic and biosafety profiles and exerted a large antitumor effect in an MCF-7 subcutaneous bearing nude mice model. Our study shows the discovery of a highly selective mTOR inhibitor using a structure-based drug discovery strategy and provides a promising antitumor candidate for future study and development.

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Section: Synthesis Of Intermediates 7c−d and 8a−dmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer

Sun,

Chu,

Zhang

et al. 2024

J. Med. Chem.

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“…Examples of such additives are stearic acid, glycerol monostearate, methyl heptanoate, ethyl heptanoate, and ethylnonanoate [ 72 , 73 , 74 ]. Moreover, it is known that some hydrophobic excipients (for example, lipid-based nanoparticles) can increase bioavailability upon exposure and use on mucous membranes and intact skin [ 75 , 76 ].…”

Section: Possible Causes Of the “Burst Release” Problemmentioning

confidence: 99%

Burst Release from In Situ Forming PLGA-Based Implants: 12 Effectors and Ways of Correction

Bakhrushina,

Sakharova,

Konogorova

et al. 2024

Pharmaceutics

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In modern pharmaceutical technology, modified-release dosage forms, such as in situ formed implants, are gaining rapidly in popularity. These dosage forms are created based on a configurable matrix consisting of phase-sensitive polymers capable of biodegradation, a hydrophilic solvent, and the active substance suspended or dissolved in it. The most used phase-sensitive implants are based on a biocompatible and biodegradable polymer, poly(DL-lactide-co-glycolide) (PLGA). Objective: This systematic review examines the reasons for the phenomenon of active ingredient “burst” release, which is a major drawback of PLGA-based in situ formed implants, and the likely ways to correct this phenomenon to improve the quality of in situ formed implants with a poly(DL-lactide-co-glycolide) matrix. Data sources: Actual and relevant publications in PubMed and Google Scholar databases were studied. Study selection: The concept of the review was based on the theory developed during literature analysis of 12 effectors on burst release from in situ forming implants based on PLGA. Only those studies that sufficiently fully disclosed one or another component of the theory were included. Results: The analysis resulted in development of a systematic approach called the “12 Factor System”, which considers various constant and variable, endogenous and exogenous factors that can influence the nature of ‘burst release’ of active ingredients from PLGA polymer-based in situ formed implants. These factors include matrix porosity, polymer swelling, LA:GA ratio, PLGA end groups, polymer molecular weight, active ingredient structure, polymer concentration, polymer loading with active ingredients, polymer combination, use of co-solvents, addition of excipients, and change of dissolution conditions. This review also considered different types of kinetics of active ingredient release from in situ formed implants and the possibility of using the “burst release” phenomenon to modify the active ingredient release profile at the site of application of this dosage form.

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Fostering the unleashing potential of nanocarriers-mediated delivery of ocular therapeutics

Datta,

Priyanka Bandi,

Colaco

et al. 2024

International Journal of Pharmaceutics

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Lipid-based nanocarriers challenging the ocular biological barriers: Current paradigm and future perspectives

Cited by 5 publications

References 197 publications

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer

Burst Release from In Situ Forming PLGA-Based Implants: 12 Effectors and Ways of Correction

Fostering the unleashing potential of nanocarriers-mediated delivery of ocular therapeutics

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