Poloxamer

Last updated
General structure with a = 2-130 and b = 15-67 Poloxamere General Formula V2.svg
General structure
with a = 2–130 and b = 15–67

Poloxamers are nonionic triblock copolymers composed of a central hydrophobic chain of polyoxypropylene (poly(propylene oxide)) flanked by two hydrophilic chains of polyoxyethylene (poly(ethylene oxide)). The word poloxamer was coined by BASF inventor, Irving Schmolka, who received the patent for these materials in 1973. [1] Poloxamers are also known by the trade names Pluronic, [2] Kolliphor (pharma grade), [3] and Synperonic. [4]

Contents

Because the lengths of the polymer blocks can be customized, many different poloxamers exist that have slightly different properties. For the generic term poloxamer, these copolymers are commonly named with the letter P (for poloxamer) followed by three digits: the first two digits multiplied by 100 give the approximate molecular mass of the polyoxypropylene core, and the last digit multiplied by 10 gives the percentage polyoxyethylene content (e.g. P407 = poloxamer with a polyoxypropylene molecular mass of 4000 g/mol and a 70% polyoxyethylene content). For the Pluronic and Synperonic tradenames, coding of these copolymers starts with a letter to define its physical form at room temperature (L = liquid, P = paste, F = flake (solid)) followed by two or three digits, The first digit (two digits in a three-digit number) in the numerical designation, multiplied by 300, indicates the approximate molecular weight of the hydrophobe; and the last digit x 10 gives the percentage polyoxyethylene content (e.g., L61 indicates a polyoxypropylene molecular mass of 1800 g/mol and a 10% polyoxyethylene content). In the example given, poloxamer 181 (P181) = Pluronic L61 and Synperonic PE/L 61.

Common poloxamer properties

PolaxamerFormulaMW (Da)HLBSource
L31PEO2PPO16PEO211001-7 [5]
L61PEO2PPO30PEO220003 [6] [7]
L81PEO3PPO43PEO327502 [7]
L101PEO4PPO59PEO438001 [7]
L121PEO5PPO68PEO544001 [7]
L42-16307-12 [8]
L62PEO8PPO30PEO825001-7 [8] [9]
L72-27501-7 [8]
L92PEO14PPO50PEO143650- [10]
L122-50001-7 [8]
L43-18507-12 [8]
L63-26507-12 [8]
P103PEO17PPO60PEO1749507-12 [8]
P123PEO20PPO69PEO2057507-12 [8]
L44-220012-18 [8]
L64PEO13PPO30PEO13290012-18 [8]
P84PEO19PPO43PEO19420012-18 [8]
P104PEO27PPO61PEO27590012-18 [8]
L35PEO11PPO16PEO11190018-23 [8] [5]
P65PEO18PPO25PEO18340012-18 [8]
P75-415012-18 [8]
P85PEO26PPO40PEO26460012-18 [8]
P105PEO37PPO56PEO37650012-18 [8]
F77-6600>24 [8]
F87PEO61PPO40PEO617700>24 [8] [7]
F127PEO100PPO65PEO1001260018-23 [8]
F38PEO42PPO16PEO424700>24 [8] [9]
F68PEO76PPO29PEO768400>24 [8] [9]
F88PEO103PPO39PEO10311400>24 [8] [9]
F98PEO118PPO45PEO11813000>24 [8] [9]
F108PEO132PPO50PEO13214600>24 [8]

Micellization and phase transitions

An important characteristic of poloxamer solutions is their temperature dependent self-assembling and thermo-gelling behavior. Concentrated aqueous solutions of poloxamers are liquid at low temperature and form a gel at higher temperature in a reversible process. The transitions that occur in these systems depend on the polymer composition (molecular weight and hydrophilic/hydrophobic molar ratio).

At low temperatures and concentrations (below the critical micelle temperature and critical micelle concentration) individual block copolymers (unimers) are present in solution. Above these values, aggregation of individual unimers occurs in a process called micellization. This aggregation is driven by the dehydration of the hydrophobic polyoxypropylene block that becomes progressively less soluble as the polymer concentration or temperature increases. The aggregation of several unimers occurs to minimize the interactions of the PPO blocks with the solvent. Thus, the core of the aggregates is made from the insoluble blocks (polyoxypropylene) while the soluble portion (polyoxyethylene) forms the shell of the micelles.

The mechanisms on the micellization at equilibrium have shown to depend on two relaxation times: (1) the first and fastest (tens of the microseconds scale) corresponds to the unimers exchange between micelles and the bulk solution and follows the Aniansson-Wall model (step-by-step insertion and expulsion of single polymer chains), [11] and (2) the second and much slower one (in the millisecond range) is attributed to the formation and breakdown of whole micellar units leading to the final micellar size equilibration.

Besides spherical micelles, elongated or worm-like micelles can also be formed. The final geometry will depend on the entropy costs of stretching the blocks, which is directly related to their composition (size and polyoxypropylene/polyoxyethylene ratio). [12] The mechanisms involved in the shape transformation are different compared to the dynamics of micellization. Two mechanisms were proposed for the sphere-to-rod transitions of block copolymer micelles, in which the micellar growth can occur by (A) fusion/fragmentation of micelles or (B) concomitant fusion/fragmentation of micelles and unimer exchange, followed by smoothing of the rod-like structures. [13]

With higher increments of the temperature and/or concentration, other phenomena can occur such as the formation of highly ordered mesophases (cubic, hexagonal and lamellar). Eventually, a complete dehydration of the polyoxypropylene blocks and the collapse of the polyoxyethylene chains will lead to clouding and/or macroscopic phase separation. This is due to the fact that hydrogen bonding between the polyoxyethylene and the water molecules breaks down at high temperature and polyoxyethylene becomes also insoluble in water.

The phase transitions can also be largely influenced by the use of additives such as salts and alcohols. The interactions with salts are related to their ability to act as water structure makers (salting-out) or water structure breakers (salting-in). Salting-out salts increase the self-hydration of water through hydrogen bonding and reduce the hydration of the copolymers, thus reducing the critical micelle temperature and critical micelle concentration. Salting-in electrolytes reduce the water self-hydration and increase the polymer hydration, therefore increasing the critical micelle temperature and critical micelle concentration. The different salts have been categorized by the Hofmeister series according to their ‘salting-out’ power. Different phase diagrams characterizing all these transitions have been constructed for most poloxamers using a great variety of experimental techniques (e.g. SAXS, Differential scanning calorimetry, viscosity measurements, light scattering).

Uses

Because of their amphiphilic structures, the polymers have surfactant properties that make them useful in industrial applications. Among other things, they can be used to increase the water solubility of hydrophobic, oily substances or otherwise increase the miscibility of two substances with different hydrophobicities. For this reason, these polymers are commonly used in industrial applications, cosmetics, and pharmaceuticals. They have also been evaluated for various drug delivery applications and were shown to sensitize drug-resistant cancers to chemotherapy.

In bioprocess applications, poloxamers are used in cell culture media for their cell cushioning effects because their addition leads to less stressful shear conditions for cells in reactors. There are grades of poloxamers commercially available specifically for cell culture, including Kolliphor P 188 Bio. [14]

In materials science, the poloxamer P123 has recently been used in the synthesis of mesoporous materials, including SBA-15.

In colloidal science, certain poloxamers such as Pluronic F-108 or Pluronic F-127, are used as steric stabilizers to prevent coalescence and/or reduce aggregation. [15] In the case of hydrophobic colloids, the poloxamer's interior hydrophobic block is absorbed into the colloid while the two hydrophilic tails remain suspended in solution, creating a steric barrier.

When mixed with water, concentrated solutions of poloxamers can form hydrogels. These gels can be extruded easily, acting as a carrier for other particles, and used for robocasting. [16]

Biological effect

Work led by Kabanov has recently shown that some of these polymers, originally thought to be inert carrier molecules, have a very real effect on biological systems independently of the drug they are transporting. [17] [18] [19] [20] The poloxamers have been shown to incorporate into cellular membranes affecting the microviscosity of the membranes. The polymers seem to have the greatest effect when absorbed by the cell as an unimer rather than as a micelle. [21]

On multi drug resistant cancer cells

Poloxamers have been shown to preferentially target cancer cells, due to differences in the membrane of these cells when compared to noncancer cells. Poloxamers have also been shown to inhibit MDR proteins and other drug efflux transporters on the surface of cancer cells; the MDR proteins are responsible for the efflux of drugs from the cells and hence increase the susceptibility of cancer cells to chemotherapeutic agents such as doxorubicin.

Another effect of the polymers upon cancer cells is the inhibition of the production of ATP in multi-drug resistant (MDR) cancer cells. The polymers seem to inhibit respiratory proteins I and IV, and the effect on respiration seems to be selective for MDR cancer cells, which may be explained by the difference in fuel sources between MDR and sensitive cells (fatty acids and glucose respectively).

The poloxamers have also been shown to enhance proto-apoptotic signaling, decrease anti-apoptoic defense in MDR cells, inhibit the glutathione/glutathione S-transferase detoxification system, induce the release of cytochrome C, increase reactive oxygen species in the cytoplasm, and abolish drug sequestering within cytoplasmic vesicles.

On nuclear factor kappa B

Certain poloxamers such as P85 have been shown not only to be able to transport target genes to target cells, but also to increase gene expression. Certain poloxamers, such as P85 and L61, have also been shown to stimulate transcription of NF kappaB genes, although the mechanism by which this is achieved is currently unknown, bar that P85 has been shown to induce phosphorylation of the inhibitory kappa.

Potential degradation by sonication

Wang et al. reported that aqueous solutions of poloxamer 188 (Pluronic F-68) and poloxamer 407 (Pluronic F-127) sonicated in the presence or absence of multi-walled carbon nanotubes (MWNTs) can became highly toxic to cultured cells. Moreover, toxicity correlated with the sonolytic degradation of the polymers. [22]

Related Research Articles

<span class="mw-page-title-main">Polyethylene glycol</span> Chemical compound

Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular weight. The structure of PEG is commonly expressed as H−(O−CH2−CH2)n−OH.

<span class="mw-page-title-main">Micelle</span> Group of fatty molecules suspended in liquid by soaps and/or detergents

A micelle or micella is an aggregate of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension. A typical micelle in water forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single-tail regions in the micelle centre.

Poloxamer 407 is a hydrophilic non-ionic surfactant of the more general class of copolymers known as poloxamers. Poloxamer 407 is a triblock copolymer consisting of a central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol (PEG). The approximate lengths of the two PEG blocks is 101 repeat units, while the approximate length of the propylene glycol block is 56 repeat units. This particular compound is also known by the BASF trade name Pluronic F-127 or by the Croda trade name Synperonic PE/F 127. BASF also offers a pharmaceutical grade, under trade name Kolliphor P 407.

A drug carrier or drug vehicle is a substrate used in the process of drug delivery which serves to improve the selectivity, effectiveness, and/or safety of drug administration. Drug carriers are primarily used to control the release of drugs into systemic circulation. This can be accomplished either by slow release of a particular drug over a long period of time or by triggered release at the drug's target by some stimulus, such as changes in pH, application of heat, and activation by light. Drug carriers are also used to improve the pharmacokinetic properties, specifically the bioavailability, of many drugs with poor water solubility and/or membrane permeability.

Small-angle X-ray scattering (SAXS) is a small-angle scattering technique by which nanoscale density differences in a sample can be quantified. This means that it can determine nanoparticle size distributions, resolve the size and shape of (monodisperse) macromolecules, determine pore sizes, characteristic distances of partially ordered materials, and much more. This is achieved by analyzing the elastic scattering behaviour of X-rays when travelling through the material, recording their scattering at small angles. It belongs to the family of small-angle scattering (SAS) techniques along with small-angle neutron scattering, and is typically done using hard X-rays with a wavelength of 0.07 – 0.2 nm. Depending on the angular range in which a clear scattering signal can be recorded, SAXS is capable of delivering structural information of dimensions between 1 and 100 nm, and of repeat distances in partially ordered systems of up to 150 nm. USAXS can resolve even larger dimensions, as the smaller the recorded angle, the larger the object dimensions that are probed.

Poly(N-isopropylacrylamide) (variously abbreviated PNIPA, PNIPAM, PNIPAAm, NIPA, PNIPAA or PNIPAm) is a temperature-responsive polymer that was first synthesized in the 1950s. It can be synthesized from N-isopropylacrylamide which is commercially available. It is synthesized via free-radical polymerization and is readily functionalized making it useful in a variety of applications.

<span class="mw-page-title-main">Temperature-responsive polymer</span> Polymer showing drastic changes in physical properties with temperature

Temperature-responsive polymers or thermoresponsive polymers are polymers that exhibit drastic and discontinuous changes in their physical properties with temperature. The term is commonly used when the property concerned is solubility in a given solvent, but it may also be used when other properties are affected. Thermoresponsive polymers belong to the class of stimuli-responsive materials, in contrast to temperature-sensitive materials, which change their properties continuously with environmental conditions. In a stricter sense, thermoresponsive polymers display a miscibility gap in their temperature-composition diagram. Depending on whether the miscibility gap is found at high or low temperatures, either an upper critical solution temperature (UCST) or a lower critical solution temperature (LCST) exists.

Pluronic P123 is a symmetric triblock copolymer comprising poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) in an alternating linear fashion, PEO-PPO-PEO. The unique characteristic of PPO block, which is hydrophobic at temperatures above 288 K and is soluble in water at temperatures below 288 K, leads to the formation of micelle consisting of PEO-PPO-PEO triblock copolymers. Some studies report that the hydrophobic core contains PPO block, and a hydrophilic corona consists of PEO block. In 30wt% aqueous solution Pluronic P123 forms a cubic gel phase.

A nanogel is a polymer-based, crosslinked hydrogel particle on the sub-micron scale. These complex networks of polymers present a unique opportunity in the field of drug delivery at the intersection of nanoparticles and hydrogel synthesis. Nanogels can be natural, synthetic, or a combination of the two and have a high degree of tunability in terms of their size, shape, surface functionalization, and degradation mechanisms. Given these inherent characteristics in addition to their biocompatibility and capacity to encapsulate small drugs and molecules, nanogels are a promising strategy to treat disease and dysfunction by serving as delivery vehicles capable of navigating across challenging physiological barriers within the body. 

<span class="mw-page-title-main">Peptide amphiphile</span>

Peptide amphiphiles (PAs) are peptide-based molecules that self-assemble into supramolecular nanostructures including; spherical micelles, twisted ribbons, and high-aspect-ratio nanofibers. A peptide amphiphile typically comprises a hydrophilic peptide sequence attached to a lipid tail, i.e. a hydrophobic alkyl chain with 10 to 16 carbons. Therefore, they can be considered a type of lipopeptide. A special type of PA, is constituted by alternating charged and neutral residues, in a repeated pattern, such as RADA16-I. The PAs were developed in the 1990s and the early 2000s and could be used in various medical areas including: nanocarriers, nanodrugs, and imaging agents. However, perhaps their main potential is in regenerative medicine to culture and deliver cells and growth factors.

Micellar solubilization (solubilization) is the process of incorporating the solubilizate into or onto micelles. Solubilization may occur in a system consisting of a solvent, an association colloid, and at least one other solubilizate.

In colloidal chemistry, the critical micelle concentration (CMC) of a surfactant is one of the parameters in the Gibbs free energy of micellization. The concentration at which the monomeric surfactants self-assemble into thermodynamically stable aggregates is the CMC. The Krafft temperature of a surfactant is the lowest temperature required for micellization to take place. There are many parameters that affect the CMC. The interaction between the hydrophilic heads and the hydrophobic tails play a part, as well as the concentration of salt within the solution and surfactants.

<span class="mw-page-title-main">Nanocarrier</span>

A nanocarrier is nanomaterial being used as a transport module for another substance, such as a drug. Commonly used nanocarriers include micelles, polymers, carbon-based materials, liposomes and other substances. Nanocarriers are currently being studied for their use in drug delivery and their unique characteristics demonstrate potential use in chemotherapy. This class of materials was first reported by a team of researchers of University of Évora, Alentejo in early 1960's, and grew exponentially in relevance since then.

The behavior of quantum dots (QDs) in solution and their interaction with other surfaces is of great importance to biological and industrial applications, such as optical displays, animal tagging, anti-counterfeiting dyes and paints, chemical sensing, and fluorescent tagging. However, unmodified quantum dots tend to be hydrophobic, which precludes their use in stable, water-based colloids. Furthermore, because the ratio of surface area to volume in a quantum dot is much higher than for larger particles, the thermodynamic free energy associated with dangling bonds on the surface is sufficient to impede the quantum confinement of excitons. Once solubilized by encapsulation in either a hydrophobic interior micelle or a hydrophilic exterior micelle, the QDs can be successfully introduced into an aqueous medium, in which they form an extended hydrogel network. In this form, quantum dots can be utilized in several applications that benefit from their unique properties, such as medical imaging and thermal destruction of malignant cancers.

<span class="mw-page-title-main">Steven Armes</span> Professor of Polymer Chemistry and Colloid Chemistry at the University of Sheffield

Steven Peter Armes is a Professor of polymer chemistry and colloid chemistry at the University of Sheffield.

Elastin-like polypeptides (ELPs) are synthetic biopolymers with potential applications in the fields of cancer therapy, tissue scaffolding, metal recovery, and protein purification. For cancer therapy, the addition of functional groups to ELPs can enable them to conjugate with cytotoxic drugs. Also, ELPs may be able to function as polymeric scaffolds, which promote tissue regeneration. This capacity of ELPs has been studied particularly in the context of bone growth. ELPs can also be engineered to recognize specific proteins in solution. The ability of ELPs to undergo morphological changes at certain temperatures enables specific proteins that are bound to the ELPs to be separated out from the rest of the solution via experimental techniques such as centrifugation.

Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. The modern form of a drug delivery system should minimize side-effects and reduce both dosage and dosage frequency. Recently, nanoparticles have aroused attention due to their potential application for effective drug delivery.

<span class="mw-page-title-main">Pentaerythritol tetraacrylate</span> Chemical compound

Pentaerythritol tetraacrylate is an organic compound. It is a tetrafunctional acrylate ester used as a monomer in the manufacture of polymers. As it is a polymerizable acrylate monomer, it is nearly always supplied with an added polymerisation inhibitor, such as MEHQ.

<span class="mw-page-title-main">Polysulfobetaine</span> Dipolar ion polymer

Polysulfobetaines are zwitterionic polymers that contain a positively charged quaternary ammonium and a negatively charged sulfonate group within one constitutional repeat unit. In recent years, polysulfobetaines have received increasing attention owing to their good biotolerance and ultralow-fouling behavior towards surfaces. These properties are mainly referred to a tightly bound hydration layer around each zwitterionic group, which effectively suppresses protein adsorption and thus, improves anti-fouling behavior. Therefore, polysulfobetaines have been typically employed as ultrafiltration membranes, blood-contacting devices, and drug delivery materials.

<span class="mw-page-title-main">Alexander Kabanov (chemist)</span>

Alexander Viktorovich Kabanov, is a Russian and American chemist, an educator, an entrepreneur, and a researcher in the fields of drug delivery and nanomedicine.

References

  1. ↑ US 3740421,Schmolka IR,"Polyoxyethylene-polyoxypropylene aqueous gels",published 1973-06-19, assigned to BASF Wyandotte Corp.
  2. ↑ "BASF - Product information the chemicals catalog - Pluronics". BASF Corporation Website. Retrieved 2008-12-09.
  3. ↑ "Poloxamers". BASF Pharma Solutions.
  4. ↑ "Synperonic". Croda.
  5. 1 2 Patel, Dhruvi; Vaswani, Payal; Sengupta, Sumana; Ray, Debes; Bhatia, Dhiraj; Choudhury, Sharmistha Dutta; Aswal, Vinod K.; Kuperkar, Ketan; Bahadur, Pratap (February 2023). "Thermoresponsive phase behavior and nanoscale self-assembly generation in normal and reverse Pluronics®". Colloid and Polymer Science. 301 (2): 75–92. doi:10.1007/s00396-022-05039-0.
  6. ↑ Pérez-Sánchez, Germán; Vicente, Filipa A.; Schaeffer, Nicolas; Cardoso, Inês S.; Ventura, Sónia P. M.; Jorge, Miguel; Coutinho, João A. P. (29 August 2019). "Rationalizing the Phase Behavior of Triblock Copolymers through Experiments and Molecular Simulations" (PDF). The Journal of Physical Chemistry C. 123 (34): 21224–21236. doi:10.1021/acs.jpcc.9b04099.
  7. 1 2 3 4 5 Oh, Kyung T; Bronich, Tatiana K; Kabanov, Alexander V (February 2004). "Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic® block copolymers". Journal of Controlled Release. 94 (2–3): 411–422. doi:10.1016/j.jconrel.2003.10.018. PMID   14744491.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Alexandridis, Paschalis; Alan Hatton, T (March 1995). "Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling". Colloids and Surfaces A: Physicochemical and Engineering Aspects. 96 (1–2): 1–46. doi:10.1016/0927-7757(94)03028-X.
  9. 1 2 3 4 5 Tsui, Hung-Wei; Wang, Jing-Han; Hsu, Ya-Hui; Chen, Li-Jen (December 2010). "Study of heat of micellization and phase separation for Pluronic aqueous solutions by using a high sensitivity differential scanning calorimetry". Colloid and Polymer Science. 288 (18): 1687–1696. doi:10.1007/s00396-010-2308-5.
  10. ↑ Guo, Chen; Liu, Hui-Zhou; Chen, Jia-Yong (December 2000). "A Fourier transform infrared study on water-induced reverse micelle formation of block copoly(oxyethylene–oxypropylene–oxyethylene) in organic solvent". Colloids and Surfaces A: Physicochemical and Engineering Aspects. 175 (1–2): 193–202. doi:10.1016/S0927-7757(00)00457-X.
  11. ↑ Aniansson EA, Wall SN (May 1974). "Kinetics of step-wise micelle association". The Journal of Physical Chemistry. 78 (10): 1024–1030. doi:10.1021/j100603a016.
  12. ↑ Alexandridis P, Hatton T (March 1995). "Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling". Colloids and Surfaces A. 96 (1–2): 1–46. doi:10.1016/0927-7757(94)03028-X.
  13. ↑ Denkova AG, Mendes E, Coppens MO (2010). "Non-equilibrium dynamics of block copolymer micelles in solution: recent insights and open questions". Soft Matter. 6 (11): 2351–2357. Bibcode:2010SMat....6.2351D. doi:10.1039/C001175B.
  14. ↑ "Poloxamers for Pharmaceutical Applications". BASF Pharma. Retrieved 2022-06-11.
  15. ↑ Kamp, Marlous; Sacanna, Stefano; Dullens, Roel P. A. (13 May 2024). "Spearheading a new era in complex colloid synthesis with TPM and other silanes". Nature Reviews Chemistry. 8 (6): 433–453. doi:10.1038/s41570-024-00603-4. PMID   38740891 . Retrieved 15 July 2024.
  16. ↑ Feilden E (2016). "Robocasting of structural ceramic parts with hydrogel inks". Journal of the European Ceramic Society. 36 (10): 2525–2533. doi:10.1016/j.jeurceramsoc.2016.03.001. hdl: 10044/1/29973 .
  17. ↑ Pitto-Barry A, Barry NP (2014-04-15). "Pluronic® block-copolymers in medicine: from chemical and biological versatility to rationalisation and clinical advances". Polymer Chemistry. 5 (10): 3291–3297. doi:10.1039/C4PY00039K. hdl: 10454/11223 . ISSN   1759-9962. S2CID   98592847.
  18. ↑ Li J, Yu F, Chen Y, Oupický D (December 2015). "Polymeric drugs: Advances in the development of pharmacologically active polymers". Journal of Controlled Release. 219: 369–382. doi:10.1016/j.jconrel.2015.09.043. PMC   4656093 . PMID   26410809.
  19. ↑ Nugraha DH, Anggadiredja K, Rachmawati H (2023-01-16). "Mini-Review of Poloxamer as a Biocompatible Polymer for Advanced Drug Delivery". Brazilian Journal of Pharmaceutical Sciences. 58. doi: 10.1590/s2175-97902022e21125 . ISSN   2175-9790. S2CID   256177315.
  20. ↑ de Castro KC, Coco JC, Dos Santos ÉM, Ataide JA, Martinez RM, do Nascimento MH, et al. (December 2022). "Pluronic® triblock copolymer-based nanoformulations for cancer therapy: A 10-year overview". Journal of Controlled Release. 353: 802–822. doi:10.1016/j.jconrel.2022.12.017. PMID   36521691. S2CID   254851024.
  21. ↑ Batrakova EV, Kabanov AV (September 2008). "Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers". Journal of Controlled Release. 130 (2): 98–106. doi:10.1016/j.jconrel.2008.04.013. PMC   2678942 . PMID   18534704.
  22. ↑ Wang R, Hughes T, Beck S, Vakil S, Li S, Pantano P, Draper RK (November 2013). "Generation of toxic degradation products by sonication of Pluronic® dispersants: implications for nanotoxicity testing". Nanotoxicology. 7 (7): 1272–1281. doi:10.3109/17435390.2012.736547. PMC   3657567 . PMID   23030523.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.