Pharmapolymers in the 21st century: Synthetic polymers in drug delivery applications

Englert, Christoph; Brendel, Johannes C.; Majdanski, Tobias C.; Yildirim, Turgay; Schubert, Stephanie; Gottschaldt, Michael; Windhab, Norbert; Schubert, Ulrich S.

doi:10.1016/j.progpolymsci.2018.07.005

Cited by 207 publications

(108 citation statements)

References 590 publications

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“…The degradation studies of the NPs at different pH values were investigated to obtain a first impression on the release of the drug from the NPs. However, it should be noted that such degradation profiles differ from the more complex environment of the endolysosomes [36].…”

Section: Degradation Profile Of the Nanoparticlesmentioning

confidence: 98%

Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity

Shkodra

Kretzer

Jordan

et al. 2020

Preprint

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Background: Dual inhibitors of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E2 synthase-1 (mPGES-1) may exert better anti-inflammatory efficacy and lower risks of adverse effects versus non-steroidal anti-inflammatory drugs. Despite these advantages, many dual FLAP/mPGES-1 inhibitors are acidic lipophilic molecules with low solubility and strong tendency for plasma protein binding that limit their bioavailability and bioactivity. Here, we present the encapsulation of the dual FLAP/mPGES-1 inhibitor BRP-187 into the biocompatible polymers acetalated dextran (Acdex) and poly(lactic-co-glycolic acid) (PLGA) via nanoprecipitation.Results: The nanoparticles containing BRP-187 were prepared by the nanoprecipitation method and analyzed by dynamic light scattering regarding their hydrodynamic diameter, by scanning electron microscopy for morphology properties, and by UV-VIS spectroscopy for determination of the encapsulation efficiency of the drug. Moreover, we designed fluorescent BRP-187 particles, which showed high cellular uptake by leukocytes, as analyzed by flow cytometry. Finally, BRP-187 nanoparticles were tested in human polymorphonuclear leukocytes and macrophages to determine drug uptake, cytotoxicity, and efficiency to inhibit FLAP and mPGES-1.Conclusion: Our results demonstrate that encapsulation of BRP-187 into Acdex and PLGA is feasible, and both PLGA-and Acdex-based particles loaded with BRP-187 are more efficient in suppressing 5-lipooxygenase product formation and prostaglandin E2 biosynthesis in intact cells as compared to the free compound, particularly after prolonged preincubation periods.

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Section: Degradation Profile Of the Nanoparticlesmentioning

confidence: 98%

Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity

Shkodra

Kretzer

Jordan

et al. 2020

Preprint

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“…To overcome these limitations, biodegradable polymeric nanoparticles are preferred these days which can offer easy drug delivery and surface modifications. It has been shown that the biodegradable polymeric nanoparticles are metabolically converted to biocompatible lactic acid, butanol, and 6-hydroxycaproic acid, all of which are considered safe by the US-FDA [149]. * The numbers refer to the numbered references in the text.…”

Section: Limitations Of the Existing Routes Of Administrationmentioning

confidence: 99%

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices. Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neurodegenerative disease, leading to the development of bradykinesia and tremors of cardinal motor functions ( Figure 2) [3]. PD models specifically show a decrease in dopamine transporters, which are responsible for dopamine uptake by dopaminergic neurons and progression of neuronal communications. Reduced Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neuro...

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“…As discussed earlier, most pharmaceutical agents have inadequate bioavailability when administered directly [ 2 , 3 ], and thus, polymeric nanocarriers provide an important tool for drug delivery. Amphiphilic block copolymers and lipids have been extensively studied as potential platforms for loading and delivering drug cargo to targeted diseased sites within the body [ 7 , 117 ]. When introduced into aqueous media, the exposure to the newly polar environment forces amphiphilic polymers to undergo microphase separation, during which chains segregate into distinct polar and non-polar phases [ 118 ].…”

Section: Amphiphilic Miktoarm Star Polymers: Self-assemblymentioning

confidence: 99%

“…As mentioned earlier, most pharmaceutical agents have poor water-solubility and low bioavailability [ 2 , 3 ]. Loading drugs into self-assembled polymeric micelles can help resolve this issue by providing solvation, enabling prolonged gradual release, and through the EPR effect, facilitate passive targeting to disease sites [ 7 , 12 , 117 ]. Owing to their tailorable architecture, superior CMCs, improved drug loading, and sustained drug release, there has been much recent interest in miktoarm star polymer-based assemblies for drug delivery [ 21 , 25 , 26 ].…”

Section: Amphiphilic Miktoarm Star Polymers: Self-assemblymentioning

confidence: 99%

Miktoarm Star Polymers: Branched Architectures in Drug Delivery

Lotocki

Kakkar

2020

Pharmaceutics

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Delivering active pharmaceutical agents to disease sites using soft polymeric nanoparticles continues to be a topical area of research. It is becoming increasingly evident that the composition of amphiphilic macromolecules plays a significant role in developing efficient nanoformulations. Branched architectures with asymmetric polymeric arms emanating from a central core junction have provided a pivotal venue to tailor their key parameters. The build-up of miktoarm stars offers vast polymer arm tunability, aiding in the development of macromolecules with adjustable properties, and allows facile inclusion of endogenous stimulus-responsive entities. Miktoarm star-based micelles have been demonstrated to exhibit denser coronae, very low critical micelle concentrations, high drug loading contents, and sustained drug release profiles. With significant advances in chemical methodologies, synthetic articulation of miktoarm polymer architecture, and determination of their structure-property relationships, are now becoming streamlined. This is helping advance their implementation into formulating efficient therapeutic interventions. This review brings into focus the important discoveries in the syntheses of miktoarm stars of varied compositions, their aqueous self-assembly, and contributions their formulations are making in advancing the field of drug delivery.

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Pharmapolymers in the 21st century: Synthetic polymers in drug delivery applications

Cited by 207 publications

References 590 publications

Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity

Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Miktoarm Star Polymers: Branched Architectures in Drug Delivery

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