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P123
P123
P123
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P123
Names
IUPAC name
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)
Other names
PEG-PPG-PEG, Pluronic P-123
Identifiers
UNII
Properties
HO(CH2CH2O)20(CH2CH(CH3)O)70(CH2CH2O)20H
Molar mass ~5800 g/mol
Appearance Waxy Paste
Density 1.018 g/mL at 25 °C
Melting point -24,99 °C at 1.013 hPa
Boiling point > 149 °C
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

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.

The nominal chemical formula of P123 is HO(CH2CH2O)20(CH2CH(CH3)O)70(CH2CH2O)20H, which corresponds to a molecular weight of around 5800 g/mol. Triblock copolymers based on PEO-PPO-PEO chains are known generically as poloxamer.

Poloxamers have behaviors similar to those of hydrocarbon surfactants, and will form micelles when placed in a selective solvent such as water. They can form both spherical and cylindrical micelles [1]

Uses

[edit]

P123 has been used in the synthesis of mesoporous materials including FDU-14.[2] Dissolved P-123 forms micelles that are used as the backbone to make structured mesoporous materials such as SBA-15.

References

[edit]
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P123

View on Grokipedia
from Grokipedia
Pluronic P123 (also known as 403) is a nonionic triblock manufactured by , characterized by a hydrophilic-hydrophobic-hydrophilic structure consisting of two poly() (PEO) blocks flanking a central poly() (PPO) block, with the specific composition represented as EO20PO70EO20. This arrangement yields a molecular weight of approximately 5800 g/mol and an content of about 30% by weight, rendering it amphiphilic with the PPO block providing hydrophobicity and the PEO blocks ensuring . As a difunctional terminating in primary hydroxyl groups, it is 100% active, relatively nontoxic, and stable in acidic or basic conditions, with low foaming properties that make it suitable for various industrial and biomedical formulations. The behavior of Pluronic P123 in aqueous solutions is a defining feature, where it forms micelles above its (CMC) of approximately 0.313 mM at 20°C, driven by the hydrophobic interactions of the PPO core encapsulating water-insoluble compounds while the PEO corona stabilizes the structure in hydrophilic environments. This micellar formation is temperature-sensitive, with increased hydrophobicity at elevated temperatures enhancing aggregation, and the overall low toxicity (LD50 > 5 g/kg in rats) supports its for applications. Additionally, its paste-like consistency at and in and organic solvents like facilitate easy processing in formulations. These properties position Pluronic P123 as a versatile in pharmaceutical and sciences, minimizing and enabling controlled release mechanisms. Pluronic P123 has gained prominence in systems, particularly for solubilizing and stabilizing hydrophobic therapeutics like or JS-K through mixed micellar formulations with other Pluronics such as F127, which enhance and exhibit superior antitumor efficacy in multidrug-resistant models compared to free s. In materials synthesis, it serves as a structure-directing agent (template) in sol-gel processes to produce ordered mesoporous silicas like SBA-15, where its block copolymer architecture controls pore size (typically 6-10 nm) and uniformity, enabling applications in and adsorption. Recent advancements include its use in lyotropic crystals for incorporating anti-inflammatory s like ibuprofen and as a modifier for MXene-based adsorbents in (as of July 2025), as well as in dual-function systems combining photodynamic and photothermal (as of October 2025) and intelligent delivery platforms for improved drug solubility and targeting, highlighting its evolving role in and sustainable technologies.

Chemical Structure

Composition and Nomenclature

P123 is a nonionic triblock copolymer composed of two hydrophilic poly(ethylene oxide) (PEO) blocks flanking a central hydrophobic poly(propylene oxide) (PPO) block, with the general structure denoted as PEOx-PPOy-PEOx, where x ≈ 20 and y ≈ 70. The repeating units consist of ethylene oxide (EO) monomers (–CH2–CH2–O–) in the outer PEO blocks and propylene oxide (PO) monomers (–CH2–CH(CH3)–O–) in the inner PPO block, yielding the chemical formula HO–(CH2CH2O)20–(CH2CH(CH3)O)70–(CH2CH2O)20–H. As part of the Pluronic series developed by , P123 follows a where the prefix "P" denotes its pasty physical form at , the first two digits ("12") approximate the molecular weight of the central PPO block divided by 100 (indicating ~1200 g/mol), and the final digit ("3") represents the approximate percentage of PEO divided by 10 (indicating ~30%).

Molecular Weight and Architecture

P123 possesses an average molecular weight of approximately 5800 Da. The polydispersity index (PDI) is typically 1.1–1.2, signifying a narrow molecular weight distribution resulting from the controlled anionic used in its synthesis. In dilute solutions below the , P123 exhibits an extended chain conformation, where the hydrophobic poly(propylene oxide) (PPO) block tends to collapse in aqueous environments owing to its low in . The for the polymer chain is approximately 2–3 nm when measured in solvents such as mixtures of and organic cosolvents that minimize polymer-solvent interactions. The triblock copolymer terminates in primary hydroxyl groups at both ends, providing reactive sites for chemical modifications, including esterification or etherification to attach functional groups for tailored applications.

Physical and Thermodynamic Properties

Solubility and Phase Behavior

P123, a triblock copolymer consisting of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) blocks, displays pronounced amphiphilicity that governs its profile across solvents. It is highly soluble in , achieving concentrations greater than 10 wt% at , as well as in polar organic solvents such as and . This stems from the hydrophilic PEO end blocks interacting favorably with polar media, while the hydrophobic PPO middle block limits dissolution in non-polar environments; consequently, P123 is insoluble in solvents like . A key aspect of P123's phase behavior in aqueous solutions is the cloud point, defined as the temperature at which the solution turns turbid due to macroscopic . For 10 wt% solutions, this occurs at approximately 90–100°C, driven primarily by the thermal dehydration of the PPO blocks, which reduces their affinity for and promotes aggregation. The cloud point exhibits modest dependence on concentration, decreasing slightly at higher loadings owing to enhanced interchain interactions. At elevated concentrations, P123 undergoes thermoreversible gelation, transitioning from a sol to a state upon heating, which is fully reversible on cooling. This phenomenon is observed above 20 wt%, with the sol-gel transition temperature for 20 wt% solutions typically ranging from 15–25°C, where increased temperature induces micellar packing into ordered structures like cubic or hexagonal phases. Overall, these properties reflect (LCST) behavior, wherein rising temperature enhances PPO block hydrophobicity through dehydration, culminating in and formation.

Micellization and Critical Micelle Concentration

Pluronic P123, a triblock copolymer with the structure poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO), undergoes micellization in aqueous solutions to form spherical micelles featuring a hydrophobic PPO core that encapsulates hydrophobic solutes and a hydrophilic PEO corona that stabilizes the assembly in . The hydrodynamic radius of these micelles is approximately 10–20 nm, as determined by techniques such as . The (CMC) of P123, above which micellization occurs, is 0.03–0.05 wt% (≈0.05–0.09 mM) at 25°C. This value decreases with increasing temperature due to enhanced dehydration of the PPO block or with the addition of salts that screen electrostatic repulsions in the corona. Similarly, incorporation of ionic liquids lowers the CMC by altering structuring around the chains. Thermodynamically, micellization is spontaneous, with the standard change (ΔG_mic) ranging from -20 to -30 kJ/mol, reflecting favorable aggregation driven by the . The process is entropy-dominated (positive ΔS), particularly at lower temperatures, while the change (ΔH) is endothermic; at higher temperatures, enthalpic contributions become more significant. The temperature dependence of the CMC follows the empirical relation log⁡(CMC)=A−B/T\log(\mathrm{CMC}) = A - B/T, where AA and BB are constants derived from van't Hoff analysis, capturing the entropy-driven nature of the transition. Certain cosolvents can lower the CMC by modulating the solvophobicity of the PPO block, though effects vary with solvent type.

Synthesis and Production

Polymerization Process

The polymerization of P123, a poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer, is primarily accomplished via anionic (AROP). This method employs sequential monomer addition to precisely control the block architecture, starting with the polymerization of (PO) to form the central hydrophobic PPO block, followed by (EO) to grow the hydrophilic PEO end blocks. A difunctional initiator, such as a (e.g., dipotassium ethyleneglycolate derived from and KOH) or a double metal (DMC) catalyst like hexacyanocobaltate, is used to ensure bifunctional chain growth in an inert solvent such as or (THF). The reaction is typically carried out at 50–100°C under a dry atmosphere to prevent moisture-induced termination, with PO addition first at higher temperatures (e.g., 80°C) for 12–24 hours to achieve 70–90% conversion, followed by EO at lower temperatures (e.g., 40°C) for controlled incorporation and high conversion (90–95%). This sequential approach leverages the differing reactivities of PO and EO, with EO polymerizing more rapidly, to yield the targeted ABA structure with low polydispersity (PDI ≈ 1.1–1.3). Post-polymerization purification is essential to isolate the product from catalysts and residuals. The mixture is filtered to remove heterogeneous catalysts like DMC complexes, then the polymer is precipitated into a non-solvent such as or , washed with water and dilute acid (e.g., 0.1 N HCl) to neutralize ends, dried over , and finally subjected to vacuum drying at reduced pressure to eliminate unreacted monomers and solvents. Key challenges in this process include minimizing and reactions, particularly with PO, which can lead to allylic termination and broader molecular weight distributions; these are mitigated by using crown ethers as complexing agents with initiators or opting for DMC catalysts that enable living without transfer. Achieving low PDI requires precise control of and monomer purity, as impurities can cause premature termination.

Commercial Manufacturing

Pluronic P123, a triblock of polyethylene oxide and polypropylene oxide, is primarily manufactured by under the Pluronic® brand name through industrial-scale processes. This production utilizes continuous reactors to synthesize the on a large scale, enabling annual output in the range of tons to meet demands across industrial and pharmaceutical sectors. 's facilities adhere to (GMP) standards for pharmaceutical-grade variants, ensuring consistency and compliance with regulatory requirements for excipients. The polymer is also distributed by suppliers such as (now part of Merck) for research and commercial applications, often under the generic name Poloxamer 403. Pharmaceutical-grade P123 meets (USP)/National Formulary (NF) specifications, including at least 99% active content, not exceeding 20 ppm, and limits on free , , and 1,4-dioxane to ensure safety and purity. Microbial limits conform to USP <61> standards for nonsterile excipients, typically requiring total aerobic microbial count ≤ 10³ CFU/g and total combined yeasts and molds ≤ 10² CFU/g, with absence of specified pathogens. P123 is packaged in forms such as prills, flakes, or powder to facilitate handling and storage, with options for bulk quantities ranging from kilograms to metric tons for industrial use. Pricing varies by purity grade and volume but generally falls in the range of $50–100 per kg for standard commercial supplies.

Applications

Pharmaceutical and Drug Delivery

Pluronic P123, a triblock copolymer composed of polyethylene glycol (PEG) and polypropylene glycol (PPO), plays a significant role in pharmaceutical formulations due to its amphiphilic nature, enabling the formation of micelles that encapsulate hydrophobic drugs for improved solubility and targeted delivery. The hydrophobic PPO core of P123 micelles effectively solubilizes poorly water-soluble therapeutics, such as the anticancer agents paclitaxel and doxorubicin, facilitating their transport in aqueous environments without the need for toxic surfactants like Cremophor EL. In micelle-based systems, P123's core-shell architecture allows for high drug loading capacities, with examples including up to 16.8 wt% for in P123-modified mixed micelles, enhancing intracellular accumulation in tumor cells. Additionally, P123 inhibits (P-gp), a key responsible for multidrug resistance (MDR), by depleting cellular ATP and disrupting membrane lipid rafts, thereby reversing resistance and potentiating the cytotoxicity of drugs like and by 2–3 orders of magnitude in MDR cancer cells. This P-gp modulation not only increases drug retention but also sensitizes resistant tumors, as demonstrated in preclinical models of and ovarian cancers. Mixed micelles combining P123 with Pluronic F127 offer sustained release profiles and improved stability, particularly for oral or intravenous administration of hydrophobic drugs. For instance, sorafenib-loaded P123/F127 micelles exhibit enhanced cytotoxicity in cancer cells compared to free drug, with lower IC50 values (7.7 μM vs. 14.8 μM) due to prolonged release and better cellular uptake; similar formulations with paclitaxel have shown 2–3-fold increases in bioavailability in vivo, attributed to reduced clearance and enhanced absorption. These mixed systems leverage P123's solubilization with F127's longer hydrophilic chains for prolonged circulation. In clinical applications, P123-based micelles serve as analogs to approved formulations like Genexol-PM, a polymeric for in and , providing cremophor-free delivery with reduced risks. P123/F127 mixtures also enable thermogelling for injectable depots, forming gels at body (around 37°C) for localized sustained release in tumors, as seen in intratumoral delivery systems with gel strengths up to 6524 N·m⁻² and tunable release rates of 0.3–2.2 μg/h·cm². Key advantages of P123 in include its low systemic and , with no significant or in preclinical models, alongside its status as an FDA-approved for pharmaceutical use. These properties minimize hemolytic activity associated with free hydrophobic drugs by encapsulation, supporting safer profiles in cancer chemotherapy.

and Templating

Pluronic P123 serves as a soft template in the sol-gel synthesis of ordered mesoporous silica materials, particularly SBA-15, where its amphiphilic triblock structure directs the formation of hexagonal arrays of cylindrical micelles that template uniform pores upon silica condensation around tetraethyl orthosilicate (TEOS). The template is subsequently removed via calcination at elevated temperatures (typically 500–550°C), yielding a highly ordered hexagonal pore structure with tunable pore diameters ranging from 2 to 10 nm, depending on synthesis conditions such as aging time and temperature. This templating approach, first demonstrated using P123 as the structure-directing agent, has enabled the production of SBA-15 with exceptional thermal stability and large surface areas (up to 1000 m²/g), making it a cornerstone for applications in catalysis and adsorption. In nanoparticle stabilization, P123's hydrophobic poly(propylene oxide) core and hydrophilic poly(ethylene oxide) shells facilitate the dispersion of hydrophobic like and metal oxides in aqueous media by adsorbing onto particle surfaces and imparting steric repulsion to prevent aggregation. For instance, P123 stabilizes reduced graphene oxide sheets at concentrations up to 1 mg/mL in water, maintaining colloidal stability for weeks, which is leveraged in formulating conductive inks for and electrochemical sensors with enhanced sensitivity. Similarly, P123 coats metal oxide nanoparticles such as or , enabling their uniform dispersion in aqueous solutions and improving performance in sensor devices by reducing agglomeration-induced signal noise. P123 is blended or coated onto (PVDF) matrices to modify membranes, where its hydrophilic segments migrate to the surface during phase inversion, significantly enhancing wettability and water flux. This surface modification increases pure water flux by 50–100% compared to unmodified PVDF membranes, attributed to reduced (from ~90° to ~40°) and improved antifouling properties without compromising mechanical integrity. Such enhancements are particularly valuable for , where higher permeability sustains long-term operation. In polymer composites, P123 incorporation into polyurethane networks tunes hydrophilicity and phase separation, thereby enhancing shape memory properties by facilitating reversible hydrogen bonding and microphase transitions. For example, blending P123 with cross-linked polyurethane and poly(L-lactide) results in biocomposites exhibiting shape fixity and recovery ratios exceeding 94%, driven by the copolymer’s ability to modulate surface energy and water uptake for thermo-responsive actuation. This approach expands the utility of polyurethane-based materials in smart textiles and biomedical devices requiring adaptive deformation. Recent developments as of 2025 include the use of P123 to modify MXene nanosheets, enhancing their adsorption capacity for heavy metal ions and organic pollutants in water remediation. P123-functionalized Ti3C2Tx MXene achieves removal efficiencies over 90% for Pb(II) and , attributed to improved dispersibility and surface interactions, supporting sustainable environmental technologies.

Biological and Safety Aspects

Biocompatibility and Toxicity

Pluronic P123, a triblock of polyethylene oxide and polypropylene oxide, is recognized by the U.S. (FDA) as a safe pharmaceutical for use in drug formulations, owing to its established profile. This status stems from extensive toxicological evaluations of s, including P123, which demonstrate low across various mammalian cell lines, with negligible effects observed at concentrations up to 0.8 μM in HL-60 and U-937 cells using MTS assays. studies further confirm minimal interference with cell viability, supporting its suitability for biological applications without significant adverse cellular responses. The toxicity profile of Pluronic P123 is characterized by low acute oral toxicity, with an LD50 exceeding 5 g/kg in rats, indicating a wide safety margin for systemic exposure. is minimal, typically below 5% at concentrations of 1 wt% in human erythrocytes, attributable to the amphiphilic structure that limits membrane disruption. Genotoxicity assessments, including the , show no mutagenic potential for closely related poloxamers like , with analogous results expected for P123 based on structural similarity. In vivo studies reveal that Pluronic P123 is biodegradable primarily through oxidation and pathways, facilitating its clearance via renal with rapid urinary elimination following intravenous administration in animal models. Subcutaneous injections in elicit minimal , as evidenced by low foreign body reactions and no significant histopathological changes in surrounding tissues. Regarding sensitization, allergic reactions to Pluronic P123 are rare, with confirming it is not a dermal sensitizer. Its safety extends to ocular and topical applications in , where it acts as a minimal irritant without inducing adverse responses in models.

Environmental Considerations

P123, a triblock consisting of poly() (PEO) and poly() (PPO) blocks, demonstrates slow biodegradability under aerobic conditions in standardized 301 tests. The central PPO block exhibits resistance to microbial degradation due to its hydrophobic nature and lack of readily oxidizable groups, limiting overall breakdown and contributing to environmental persistence. In terms of ecotoxicity, P123 shows low to aquatic organisms, with an LC50 of 649 mg/L for in 48-hour exposure tests, indicating minimal short-term harm to invertebrates at environmentally relevant concentrations. Furthermore, its micellar form exhibits no significant potential due to high solubility and polymeric structure. P123 is registered under the European Union's REACH regulation as a non-hazardous substance for industrial uses, reflecting its assessed low environmental risk profile. In wastewater treatment processes, over 90% removal efficiency is typically achieved through adsorption onto sludge and settling, preventing substantial release into receiving waters. Regarding sustainability, P123 is derived from petroleum-based monomers such as and , with limited progress in developing fully bio-based alternatives for Pluronic-type copolymers due to challenges in replicating their amphiphilic properties from renewable feedstocks. Its characteristics aid in environmental dispersion but do not mitigate persistence concerns addressed elsewhere.

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