Unusual Enthalpy Driven Self Assembly at Room Temperature with Chitosan Amphiphiles

Author(s): Uchechukwu Odunze, Fionn O'Brien, Lisa Godfrey, Andreas Schätzlein, Ijeoma Uchegbu*.

Journal Name: Pharmaceutical Nanotechnology

Volume 7 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: GCPQ (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl- 6-O-glycolchitosan) is a self-assembling polymer being investigated as a pharmaceutical nano-carrier. GCPQ nanoparticles shuttle drugs across biological barriers, improving drug performance. The exact chemistry of GCPQ is varied by the relative proportion of hydrophobic (N-palmitoyl) and hydrophilic (quaternary ammonium) groups and molecular weight.

Objective: We hypothesised that the thermodynamics of self-assembly is controlled by the polymer molecular weight and hydrophobicity.

Method: The thermodynamics of self-assembly was investigated using isothermal calorimetry.

Results: GCPQs (Mw = 8-15 kDa) formed micellar aggregates at critical micellar concentrations of 1-2.4 µM at 25°C and micellisation was unusually enthalpy driven. There was a positive correlation between ΔHmic and mole% quaternary groups (Q): ΔHmic = 3.8 Q- 159 (r2 = 0.93) and a negative correlation between ΔHmic and molecular weight (Mw): ΔHmic = -13.5 Mw-26.3 (r2 = 0.99).

Conclusion: These findings provide insights into the positive drivers of stable selfassemblies, namely hydrophobicity and molecular weight, as both hydrophobicity and molecular weight are associated with an increased enthalpy contribution to micellisation.

Keywords: Colloids, critical micelle concentration (CMC), endothermic, enthalpy, entropy, exothermic, GCPQ, micelle, nanomedicine, polymer, thermodynamics.

[1]
Borisov OV, Halperin A. Micelles of Polysoaps. Langmuir 1995; 11(8): 2911-9.
[2]
Wang W, Qu XZ, Gray AI, Tetley L, Uchegbu IF. Self-assembly of cetyl linear polyethylenimine to give micelles, vesicles, and dense nanoparticles. Macromolecules 2004; 37(24): 9114-22.
[3]
Discher B, Won YY, Ege JCM, Bates FS, Discher D, Hammer DA. Polymersomes: tough vesicles made from diblock copolymers. Science 1999; 284: 1143-6.
[4]
Wang W, Tetley L, Uchegbu IF. The level of hydrophobic substitution and the molecular weight of amphiphilic poly-L-lysine-based polymers strongly affects their assembly into polymeric bilayer vesicles. J Colloid Interface Sci 2001; 237(2): 200-7.
[5]
Uchegbu IF, Carlos M, McKay C, Hou XL, Schatzlein AG. Chitosan amphiphiles provide new drug delivery opportunities. Polym Int 2014; 63(7): 1145-53.
[6]
Martin C, Aibani N, Callan JF, Callan B. Recent advances in amphiphilic polymers for simultaneous delivery of hydrophobic and hydrophilic drugs. Ther Deliv 2016; 7(1): 15-31.
[7]
Akiyoshi K, Nishikawa T, Mitsui Y, Miyata T, Kodama M, Sunamoto J. Self-assembly of polymer amphiphiles: thermodynamics of complexation between bovine serum albumin and self-aggregate of cholesterol-bearing pullulan. Colloids Surf A Physicochem Eng Asp 1996; 112(2-3): 91-5.
[8]
Suwa M, Hashidzume A, Morishima Y, Nakato T, Tomida M. Self-association behavior of hydrophobically modified poly (aspartic acid) in water studied by fluorescence and dynamic light scattering techniques. Macromolecules 2000; 33(21): 7884-92.
[9]
Sharma KS, Durand G, Gabel F, et al. Non-ionic amphiphilic homopolymers: synthesis, solution properties, and biochemical validation. Langmuir 2012; 28(10): 4625-39.
[10]
Diab C, Winnik FM, Tribet C. Enthalpy of interaction and binding isotherms of non-ionic surfactants onto micellar amphiphilic polymers (amphipols). Langmuir 2007; 23(6): 3025-35.
[11]
Chandler D. Interfaces and the driving force of hydrophobic assembly. Nature 2005; 437(7059): 640-7.
[12]
Florence AT, Attwood D. Physicochemical principles of pharmacy. 4th ed. London: McMillan Press Ltd 2006.
[13]
Siew A, Le H, Thiovolet M, Gellert P, Schatzlein A, Uchegbu I. Enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles. Mol Pharm 2012; 9(1): 14-28.
[14]
Cheng WP, Gray AI, Tetley L, Hang TLB, Schatzlein AG, Uchegbu IF. Polyelectrolyte nanoparticles with high drug loading enhance the oral uptake of hydrophobic compounds. Biomacromolecules 2006; 7(5): 1509-20.
[15]
Chooi KW, Simao Carlos MI, Soundararajan R, et al. Physical characterisation and long-term stability studies on quaternary ammonium palmitoyl glycol chitosan (GCPQ)--a new drug delivery polymer. J Pharm Sci 2014; 103(8): 2296-306.
[16]
Serrano DR, Lalatsa A. Dea-Ayuela, et al. Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles. Mol Pharm 2015; 12(2): 420-31.
[17]
Qu XZ, Khutoryanskiy VV, Stewart A, Rahman S, et al. Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. Biomacromolecules 2006; 7(12): 3452-9.
[18]
Godfrey L, Garrett NL, Lalatsa A, Soundararajan R, et al. Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia. J Control Release 2018; 270: 135-44.
[19]
Paula S, Sus W, Tuchtenhagen J, Blume A. Thermodynamics of micelle formation as a function of temperature - a high-sensitivity titration calorimetry study. J Phys Chem 1995; 99(30): 11742-51.
[20]
Chooi KW, Gray AI, Tetley L, Fan YL, Uchegbu IF. The molecular shape of poly(propylenimine) dendrimers has a profound effect on their self assembly. Langmuir 2010; 26: 2301-16.
[21]
Marsh D. Thermodynamics of phospholipid self-assembly. Biophys J 2012; 102(5): 1079-87.
[22]
Matulis D, Bloomfield VA. Thermodynamics of the hydrophobic effect. II. Calorimetric measurement of enthalpy, entropy, and heat capacity of aggregation of alkylamines and long aliphatic chains. Biophys Chem 2001; 93(1): 53-65.
[23]
Chatterjee A, Moulik S, Sanyal S, Mishra B, Puri P. Thermodynamics of micelle formation of ionic surfactants: a critical assessment for sodium dodecyl sulfate, cetyl pyridinium chloride and dioctyl sulfosuccinate (Na salt) by microcalorimetric, conductometric, and tensiometric measurements. J Phys Chem 2001; 105(51): 12823-31.
[24]
Tanford C. The hydrophobic effect: formation of micelles and biological membranes. New York: John Wiley and Sons 1980.
[25]
Gill SJ, Wadso I. Equation of state describing hydrophobic interactions. Proc Natl Acad Sci USA 1976; 73(9): 2955-8.
[26]
Kronberg B, Costas M, Silveston R. Thermodynamics of the hydrophobic effect in surfactant solutions- micellization and adsorption: 13th IUPAC International Conference on Chemical Thermodynamics; 1994 Jul 17-22; Clermont Ferrand, France. Berlin: Walter de Gruyter GmbH 1995.
[27]
Shimizu S, Pires PAR, El Seoud OA. Thermodynamics of micellization of benzyl(2-acylaminoethyl) dimethylammonium chloride surfactants in aqueous solutions: a conductivity and titration calorimetry study. Langmuir 2004; 20(22): 9551-9.
[28]
Ahmad S, Johnston BF, Mackay SP, et al. In silico modelling of drug-polymer interactions for pharmaceutical formulations. J R Soc Interface 2010; 7: S423-33.
[29]
Ma CD, Wang C, Acevedo-Velez C, Gellman SH, Abbott NL. Modulation of hydrophobic interactions by proximally immobilized ions. Nature 2015; 517(7534): 347-50.
[30]
Davis JG, Gierszal KP, Wang P, Ben-Amotz D. Water structural transformation at molecular hydrophobic interfaces. Nature 2012; 491(7425): 582-5.
[31]
Stodghill SP, Smith AE, O’Haver JH. Thermodynamics of micellization and adsorption of three alkyltrimethylammonium bromides using isothermal titration calorimetry. Langmuir 2004; 20(26): 11387-92.
[32]
Corkill J, Goodman J, Harrold S, Tate J. Thermodynamics of comicellization of ionic detergents. T Faraday Soc 1966; 62: 994-1001.
[33]
Tong W, Zheng Q, Shao S, Lei Q, Fang W. Critical micellar concentrations of quaternary ammonium surfactants with hydroxyethyl substituents on headgroups determined by isothermal titration calorimetry. J Chem Eng Data 2010; 55(9): 3766-71.
[34]
Alexandridis P, Nivaggioli T, Hatton TA. Temperature effects on structural properties of pluronic P104 and F108 PEO-PPO-PEO block copolymer solutions. Langmuir 1995; 11(5): 1468-76.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 7
ISSUE: 1
Year: 2019
Page: [57 - 71]
Pages: 15
DOI: 10.2174/2211738507666190311123401

Article Metrics

PDF: 26
HTML: 7
EPUB: 1