HPMA Copolymer-Based Nanomedicines in Controlled Drug Delivery

Recently, numerous polymer materials have been employed as drug carrier systems in medicinal research, and their detailed properties have been thoroughly evaluated. Water-soluble polymer carriers play a significant role between these studied polymer systems as they are advantageously applied as carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, antimicrobial molecules, or multidrug resistance inhibitors. Covalent attachment of carried molecules using a biodegradable spacer is strongly preferred, as such design ensures the controlled release of the drug in the place of a desired pharmacological effect in a reasonable time-dependent manner. Importantly, the synthetic polymer biomaterials based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are recognized drug carriers with unique properties that nominate them among the most serious nanomedicines candidates for human clinical trials. This review focuses on advances in the development of HPMA copolymer-based nanomedicines within the passive and active targeting into the place of desired pharmacological effect, tumors, inflammation or bacterial infection sites. Specifically, this review highlights the safety issues of HPMA polymer-based drug carriers concerning the structure of nanomedicines. The main impact consists of the improvement of targeting ability, especially concerning the enhanced and permeability retention (EPR) effect.

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Multifunctional NaLnF4@MOF-Ln Nanocomposites with Dual-Mode Luminescence for Drug Delivery and Cell Imaging

Nanomaterials ◽

10.3390/nano9091274 ◽

2019 ◽

Vol 9 (9) ◽

pp. 1274 ◽

Cited By ~ 6

Author(s):

Wang ◽

Zhao ◽

Gao ◽

Xu ◽

Wang ◽

...

Keyword(s):

Drug Delivery ◽

Cell Imaging ◽

Drug Carrier ◽

Drug Carriers ◽

Water Soluble ◽

Dual Mode ◽

Metal Organic ◽

Lanthanide Metal ◽

Good Biocompatibility ◽

Anti Stokes

Multifunctional nanomaterials for bioprobe and drug carrier have drawn great attention for their applications in the early monitoring the progression and treatment of cancers. In this work, we have developed new multifunctional water-soluble NaLnF4@MOF-Ln nanocomposites with dual-mode luminescence, which is based on stokes luminescent mesoporous lanthanide metal–organic frameworks (MOFs-Y:Eu3+) and anti-stokes luminescent NaYF4:Tm3+/Yb3+ nanoparticles. The fluorescence mechanism and dynamics are investigated and the applications of these nanocomposites as bioprobes and drug carriers in the cancer imaging and treatment are explored. Our results demonstrate that these nanocomposites with the excellent two-color emission show great potential in drug delivery, cancer cell imaging, and treatment, which are attributed to the unique spatial structure and good biocompatibility characteristics of NaLnF4@MOF-Ln nanocomposites.

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Improved pH-Controlled Release of Phenformin from Low-Defect Graphene Compared to Graphene Oxide

10.26434/chemrxiv.14731695 ◽

2021 ◽

Author(s):

Abdelnour Alhourani ◽

Jan-Lukas Førde ◽

Lutz Eichacker ◽

Lars Herfindal ◽

Hanne Hagland

Keyword(s):

Graphene Oxide ◽

Controlled Release ◽

Graphene Nanosheets ◽

Drug Carrier ◽

Chemical Vapor ◽

Drug Carriers ◽

Covalent Attachment ◽

Cancer Drug ◽

Delivery Options ◽

Ph Controlled

Graphene-based drug carriers provide a promising addition to current cancer drug 8 delivery options. Increased accessibility of high-quality graphene made by plasma- enhanced chemical vapor deposition (PE-CVD) makes it an attractive material to re-visit in comparison to the widely studied graphene oxide (GO) in drug delivery. Here we show the potential of re-purposing the metabolic drug phenformin for cancer treatment in terms of stability, binding, and pH-controlled release. Using covalent attachment of polyethylene glycol (PEG) onto pristine (PE-CVD) graphene, we show that the PEG stabilized graphene nanosheets (PGNS) drug carrier is stable in aqueous solutions, exhibit a higher binding affinity towards phenformin than conventional GO. Moreover, we experimentally demonstrate an improved drug release in PGNS than GO in pH levels lower than physiological conditions comparable to an acidic tumor microenvironment.

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Polymer-Dispersed Liquid Crystals: Boojums at Work

MRS Bulletin ◽

10.1557/s0883769400057869 ◽

1991 ◽

Vol 16 (1) ◽

pp. 22-28 ◽

Cited By ~ 55

Author(s):

J. William Doane

Keyword(s):

Refractive Index ◽

Liquid Crystal ◽

Liquid Crystals ◽

Polarized Light ◽

Solid Particles ◽

Water Soluble ◽

The Other ◽

Polymer Materials ◽

Water Soluble Polymer ◽

Polymer Dispersed

The idea of dispersing micron-size birefringent particles in a polymer to selectively scatter light is not new. In the 1930s Land patented a light polarizing material in which small, oriented solid crystallites were suspended in a clear polymer. The polymer material was selected so that its refractive index matched one of the principal refractive indices of the crystallites while the other did not. The resuit was a light polarizer tha t would pass one component of polarized light but scatter the other component out of the beam path.This idea was substantially expanded by the introduction of liquid crystals as the birefringent material. The orientation of the particles (in this case droplets), and hence the refractive index match and the scattering, could be controlled by an electric field. Such a material could be used as a light shutter for either unpolarized or polarized light. In the mid-1970s this basic concept was applied by Hilsum, but having no way to disperse droplets of liquid crystals in a polymer, he did the opposite and put optically isotropic solid particles in the birefringent liquid crystal.Although Hilsum demonstrated the concept, no commercial device was produced, probably because the shutter contrast was limited. Since then several ways have been found to disperse droplets in a polymer: filling the pores of a microfilter; emulsifying the liquid crystal in a water soluble polymer; and using phase separation methods to create a dispersion of droplets in non-aqueous polymer materials.

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Water-soluble polymer materials as complexing reagents for the separation of metal ions using membrane filtration

Polymers for Advanced Technologies ◽

10.1002/pat.791 ◽

2006 ◽

Vol 17 (11-12) ◽

pp. 865-871 ◽

Cited By ~ 6

Author(s):

Bernabé L. Rivas ◽

S. Amalia Pooley ◽

Eduardo Pereira ◽

Erika Montoya ◽

Rocío Cid ◽

...

Keyword(s):

Metal Ions ◽

Membrane Filtration ◽

Water Soluble ◽

Polymer Materials ◽

Soluble Polymer ◽

Water Soluble Polymer ◽

Separation Of Metal Ions

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Molecular Dynamics Simulations of Glycyrrhizic Acid Aggregates as Drug-Carriers for Paclitaxel

Current Drug Delivery ◽

10.2174/1567201816666190313155117 ◽

2019 ◽

Vol 16 (7) ◽

pp. 618-627 ◽

Cited By ~ 3

Author(s):

Mumtaz Hussain

Keyword(s):

Molecular Dynamics ◽

Glycyrrhizic Acid ◽

Oral Absorption ◽

Drug Carrier ◽

Drug Carriers ◽

Water Soluble ◽

Aggregation Behavior ◽

Dynamics Simulation ◽

Aqueous Environment ◽

Dynamics Simulations

Background: Glycyrrhizic acid (GA) is a glycoside that has shown considerable promise as a penetration enhancer and drug carrier to improve the absorption of poorly water-soluble drugs. The aggregation behavior of GA and its ability to form large micelles at higher solution concentrations are thought to contribute to these bioavailability enhancing properties. The oral absorption of Paclitaxel (PTX) for example, an anti-cancer agent which exhibits poor oral bioavailability, has been found to significantly increase in the presence of GA. Methods: In an attempt to visualize the aggregation behavior of GA and its subsequent association with PTX, 100 ns molecular dynamics simulation of a 5 mM aqueous solution of GA with 10 molecules of PTX was conducted using GROMACS and an all-atom forcefield. Results: Aggregation of GA molecules was found to occur quickly at this level of saturation leading to two stable aggregates of 13 and 17 GA molecules with an effective radius of 10.17 nm to 10.92 nm. These aggregates form not in isolation, but together with PTX molecule embedded within the structures, which reduces the number of interactions and hydrogen-bonding with water. Conclusion: GA aggregation occurs around PTX molecules in solution, forming co-joined GA-PTX cluster units at a ratio of 3:1. These clusters remain stable for the remainder of the 100ns simulation and serve to isolate and protect PTX from the aqueous environment.

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Improved pH-Controlled Release of Phenformin from Low-Defect Graphene Compared to Graphene Oxide

10.26434/chemrxiv.14731695.v1 ◽

2021 ◽

Author(s):

Abdelnour Alhourani ◽

Jan-Lukas Førde ◽

Lutz Eichacker ◽

Lars Herfindal ◽

Hanne Hagland

Keyword(s):

Graphene Oxide ◽

Controlled Release ◽

Graphene Nanosheets ◽

Drug Carrier ◽

Chemical Vapor ◽

Drug Carriers ◽

Covalent Attachment ◽

Cancer Drug ◽

Delivery Options ◽

Ph Controlled

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Synthesis of Poly(ethylene glycol) Block Copolymers as Potential Water-Soluble Drug Carriers

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19951765 ◽

1995 ◽

Vol 60 (10) ◽

pp. 1765-1780 ◽

Cited By ~ 11

Author(s):

Michal Pechar ◽

Jiří Strohalm ◽

Karel Ulbrich

Keyword(s):

Block Copolymers ◽

Ethylene Glycol ◽

Glutamic Acid ◽

Drug Carrier ◽

Drug Carriers ◽

Water Soluble ◽

Poly Ethylene Glycol ◽

Water Soluble Drug ◽

Poly Ethylene ◽

The Relationship

The synthesis of a model water-soluble drug carrier based on poly(ethylene glycol) (PEG) block copolymers is described. In the copolymers, two blocks of PEG are linked by a biodegradable oligopeptide or amino acid linkage containing the glutamic acid residue. 4-Nitroaniline as a drug model is attached to the γ-carboxyl group of glutamic acid of the polymer carrier via an enzymatically degradable oligopeptide spacer. The oligopeptides used were potential substrates for chymotrypsin. The relationship between the structure of oligopeptides linking two PEG blocks and the rate of chymotrypsin-catalyzed polymer chain degradation as well as the relationship between the structure of the spacer and kinetics of drug model release from the carrier after incubation in chymotrypsin solution is discussed in detail. The results showed that by modifying the structure of oligopeptides in the polymer construct, changes in the rates of both polymer degradation and the drug model release can be achieved in a very broad range.

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Synthesis and Anchoring of Antineoplastic Ferrocene and Phthalocyanine Derivatives on Water-Soluble Polymeric Drug Carriers Derived from Lysine and Aspartic Acid

Metal-Based Drugs ◽

10.1155/2008/217573 ◽

2008 ◽

Vol 2008 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

M. David Maree ◽

Eberhard W. Neuse ◽

Elizabeth Erasmus ◽

Jannie C. Swarts

Keyword(s):

Aspartic Acid ◽

Drug Carrier ◽

Drug Carriers ◽

Water Soluble ◽

Amide Bond ◽

Drug Conjugates ◽

Synthetic Strategy ◽

Coupling Reagent ◽

Polymeric Drug ◽

Derivatives Of

The general synthetic strategy towards water-soluble biodegradable drug carriers and the properties that they must have are discussed. The syntheses of water-soluble biodegradable copolymers of lysine and aspartic acid as potential drug-delivering devices, having amine-functionalised side chains are then described. Covalent anchoring of carboxylic acid derivatives of the antineoplastic ferrocene and photodynamically active phthalocyanine moieties to the amine-containing drug carrier copolymers under mild coupling conditions has been achieved utilising the coupling reagent O-benzotriazolyl-N,N,N′,N′-tetramethyluronium hexafluorophosphate to promote formation of the biodegradable amide bond. Even though the parent antineoplastic ferrocene and phthalocyanine derivatives are themselves insoluble in water at pH < 7, the new carrier-drug conjugates that were obtained are well water-soluble.

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Neurotoxicity and Neuroprotective Effects of Polyimides (PI) and Polyphenylenevinylene (PPV) against Hydrogen Peroxide (H2O2)

Scientific Research Journal ◽

10.24191/srj.v8i2.5049 ◽

2011 ◽

Vol 8 (2) ◽

pp. 33

Author(s):

Norfaezah Mazalan ◽

Mazatulikhma Mat Zain ◽

Nor Saliyana Jumali ◽

Norhanim Mohalid ◽

Zurina Shaameri ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Drug Delivery Systems ◽

Neuronal Cells ◽

Water Soluble ◽

Brain Delivery ◽

Specific Therapy ◽

Neuroprotective Effects ◽

Water Soluble Polymer ◽

Site Specific ◽

Novel Drugs

Recently, research and development in the field of drug delivery systems (DDS) facilitating site-specific therapy has reached significant progression. DDS based on polymer micelles, coated micro- and nanoparticles, and various prodrug systems including water-soluble polymer have been prepared and extensively studied as novel drugs designed for cancer chemotherapy and brain delivery. Since polymers are going to be used in human, this study has the interest of testing two types of polymer, polyimides (PI) and polyphenylenevinylene (PPV) on neuronal cells. The objective of this study was to determine the possible neurotoxicity and potential neuroprotective effects of PI and PPV towards SH-SY5Y neuronal cells challenged by hydrogen peroxide (H2O2) as an oxidant. Cells were pretreated with either PI or PPV for 1 hour followed by incubation for 24 hour with 100 µM of H2O2. MTS assay was used to assess cell viability. Results show that PI and PPV are not harmful within the concentration up to 10 µM and 100 µM, respectively. However, PI and PPV do not protect neuronal cells against toxicity induced by H2O2 or further up the cell death.

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Pharmacognostical Standardization and Pharmacological Potential of Elaeocarpus ganitrus Leaves as an Antiulcer Agent

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.4.3 ◽

2018 ◽

Vol 11 (4) ◽

pp. 4162-4169

Author(s):

Mayank Kulshreshtha ◽

Manjul Pratap Singh

Keyword(s):

Skin Diseases ◽

Scientific Data ◽

Water Soluble ◽

Histopathological Analysis ◽

Phytochemical Analysis ◽

Dependent Manner ◽

Soluble Extract ◽

Biochemical Studies ◽

Pharmacological Potential ◽

Dose Dependent

Elaeocarpus ganitrus Roxb, (E. ganitrus) known as Rudraksha belongs to family- Eleocarpaceae. It has a reflecting position in Hinduism and Ayurveda whereas traditionally it has mentioned to cure various health problems like fever, skin diseases, mental problems, wound healing etc. The present study was designed to study the microscopic and macroscopic analysis, physiochemical parameters, quantitative microscopy, phytochemical screening of E. ganitrus leaves as per WHO guidelines and evaluate the antiulcer potential of aqueous extract of E. ganitrus (AEEG) and ethanolic extract of E. ganitrus (EEEG) at the doses of 200 mg/kg and 400 mg/kg using pylorus ligation induced ulcers model, biochemical parameters. Hepatic, cardiac, hematological parameters have also done to find out the effect of different extracts on other major organs. Microscopic analysis proved the presence of covering trichomes, upper epidermis, lower epidermis, stomata, phloem, xylem etc. Ash value, water soluble ash, acid soluble ash, water soluble extract, alcohol soluble extract, loss on drying, swelling index, foaming index found to be 4.3 ± 0.52, 0.2 ± 0.33, 2.0 ± 0.2, 13.7 ± 0.25, 12.5 ± 0.55, 9.8 ± 0.23, 3.6 ± 0.04, more than 100. Different quantitative parameters were found out. Phytochemical analysis of different extracts showed the presence of various primary and secondary metabolite like alkaloids, glycosides, tannin, phenolic compounds etc. Pharmacological potential showed that extracts treated, and sucralfate treated groups showed significantly decreases in ulcer index in all above-mentioned models, biochemical studies clearly showed significant decreases in volume, pH, free acidity, total acidity of gastric content and increases in gastric mucus parameters like protein, total hexoses, hexosamine, fucose, sialic acid and DNA level. The level of antioxidant enzymes like LPO (Lipid peroxidation), SOD (Superoxide dimutase) were decreased and CAT (Catalase) level was increased. Level of PC (Plasma corticosterone) was decreased. Hematological, hepatic, cardiac parameters found to be normal during extracts treatment. Histopathological analysis clearly supports the biochemical studies at various doses and it was found to be effective in dose dependent manner. The obtained scientific data may be helpful to prepare the monograph of the plant and E. ganitrus has antiulcer potential in a dose dependent. Detailed study needed for better exposure of plant.

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