Research Article

J Sci Discov (2020); 4(2):jsd20037; DOI:10.24262/jsd.4.2.20037; 
Received August 10th, 2020, Revised October 10th, 2020, Accepted October 29th, 2020, Published November 10th, 2020.

“To gel or not to gel”– process variables investigation of polylactide-based nano-organogel suggests the missing link

Frank O. Ohwoavworhua^1,2,*, James W. Mitchell²

¹Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington DC, USA

²Department of Chemical and Biomolecular Engineering, College of Engineering and Architecture, Howard University, Washington DC, USA

* Correspondence:Dr. Frank O. Ohwoavworhua, Department of Chemical and Biomolecular Engineering, College of Engineering and Architecture, Howard University, Washington DC, USA. Email: frankohwo@gmail.com.

“To gel or not to gel” in supramolecular gel science is shroud with mixed frustration-to-mysteries even after over two decades of vigorous research. Efforts to resolve the gel puzzle came strongly when major players in this field correlated molecular gelation with solvent properties, while adopting solvent-gelator – a two-phase system as the rational way – an approach that led to the reassessment of over 100’s of individual gelators by various groups using Meta analysis. Despite the several efforts, the gel puzzle still exists. It is our believe that understanding the effect of process variables in a few case-by-case studies of “privileged” scaffolds gelators using the design of experiments approach will provide a useful insight into the gelation mechanisms. Hence in this study, we have used simple 3² factorial designs to examine the effect of process variables of an in-situ formed PLA-based nano-organogel. We found that low stirring rate, the presence of tert-butyl catechol (TBC) and continuous gas flow (in this case nitrogen) are necessary experimental conditions for the nano-organogel to form. We concluded that the presence of continuous nitrogen gas flow for gel formation, suggests that gelation should also be viewed as a three-phase system (solvent-gelator-gas), rather than, entirely, the solvent-gelator two-phase system that has always been adopted. 

Keywords:Gel, supramolecular gel, factorial designs, nano-organogel, process variables

*Frank O. Ohwoavworhua (corresponding author: frankohwo@gmail.com) carried out the experimental synthesis, characterizations and investigation of the effects of process variables, as well as wrote the main manuscript. James W. Mitchell supervised all aspects of the work. Both authors reviewed the manuscript.

The authors declare no competing interests

None

1. Wang, Y., Lovrak, M., Liu, Q., Maity, C., Le Sage V. A. A., Guo, X., Eelkema, R. & van Esch, J. H. Hierachically compartmentalized supramolecular gels through multilevel self-sorting. JACS2018; 141(7): 2847-2851.
2. Basu N, Chakraborty A and Ghosh R. Carbohydrate derived organogelators and the corresponding functional gels developed in recent time. Gel2018; 4(2): 52.
3. Singh PW and Singh RS. A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation. Beilstein J. Organic Chem.2017; 13: 138-149.
4. Nikiforidis CV and Scholten E. Self-assemblies of lecithin and alpha tocopherol as gelators of liquid materialsRSC Adv 2014; 4: 2466-2473 (2014).
5. Ajayaghosh A and Praveen VK. π – Organogels of self-assembled p – phenylenevinylenes: soft materials with distinct size, shape and functions. Chem. Res.2007; 40: 644-656.
6. George M and Weiss RG. Molecular organogels. Soft matter comprised of low molecular mass organic gelators and organic liquids. Chem. Res.2006; 39:489-497.
7. Debnath S. et al. Tunable supramolecular gels by varying thermal history. Chemistry: A Europ. J.2019; doi: 10. 1002/chem.201806281.
8. Weiss RG. Controlling variables in molecular gel science: how can we improve the state of the art?Gel 2018; 4(2): 25.
9. Lan Y, Corradini MG, Weiss RG, Raghavan SR, Rogers MA. To gel or not to gel: correlating molecular gelation with solvent parameters. Chem Soc Rev2015; DOI: 10.1039/c5cs00136f.
10. Dastidar P. Designing supramolecular gelators: challenges, frustrations and hopes. Gels2019; 5:15.
11. Edwards W and Smith KD. Chiral assembly preferences and directing effects in supramolecular two-component organogels. Gels2018; 4:31-48.
12. Sundararajan K. “Design of Experiments – a primer – iSixSigma. (2016).
13. Armstrong NA. Pharmaceutical Experimental Design and Interpretation. 2^nd New York: Informa Healthcare. 2010; 83p.
14. Dillen K, Vandervoort J, Van den GM, Verheyden L, Ludwig A. Factorial design, physicochemical characterization and activity of ciprofloxacin-PLGA nanoparticles. Int J Pharm2004; 275:171-187.
15. Zambaux FM, Bonneaux F, Gref R, Maincent P, Dellacherie E, Alonso JM, Labrude P, Vigneron C. Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by double emulsion method. J Control Release1998; 50: 31-40.
16. Ohwoavworhua FO and Mitchell JW. Synthesis and spectroscopic signatures of a novel polylactide-based nano-organogel. Drug Discov (in press).
17. Mallia CJ and Baxendale IR. The use of gases in flow synthesis. Organic Process Res Dev 2016; 20(2):327-360.
18. Birdi KS. Surface Chemistry Essentials. FL: CRC Press. 2014; 211-236p.
19. Florence AT, Attwood D. Physicochemical Principles of Pharmacy. 5^th London: Pharmaceutical Press. 2011; 347 p.
20. dos Santos S, Antunes EF, Medronho B, dos Santos T. Amphiphilic molecules in drug delivery systems. In: Coelho J (ed), Drug Delivery Systems: Advanced Technologies Potentially Applicable in Personalised Treatment, Advances in Predictive, Preventive and Personalised Medicine 2013; 4, DOI 10.1007/978-94-007-6010-3_2, Springer Science+Business Media Dordrecht.
21. Huang S, Onyari JM. Multicomponent polymers poly (lactic acid) macromonomers with methacrylate terminal and copolymers of poly (2-hydroxyethyl methacrylate). JMS Pure Appl Chem1996; A33: 571-584.
22. Eguiburu JL, Fernandez-Berridi MJ, San Roman J. Functionalization of poly(L- lactide) macromonomers by ring-opening polymerization of L-lactide initiated with hydroxyethyl methacrylate-aluminium alkoxides. Polymer1995; 36:173-179.
23. Eguiburu JL, Fernandez-Berridi MJ, Cossio FP, San Roman J. Ring-opening polymerization of L-lactide initiated by (2-Mathacryloxy) ethyloxy-aluminium trialkoxides. 1. Kinetics. Macromolecules1999; 32:8252-8258.
24. Pavia LD, Lampman MG, Kriz SG, Vyvyan AJ. Introduction to Spectroscopy, 4^th CA, Belmont: Cengage Learning. 2009; 15-125p.
25. Kawaguchi S, Ito K. Dispersion polymerization. Adv Polym Sci2005; 175:299-328.
26. Langer K, Marburger C, Berthold A, Kreuter J, Stieneker F. Methylmethacrylate sulfopropylmethacrylate copolymer nanoparticles for drug delivery. Part 1: preparation and physicochemical characterization. Int J Pharm1996; 137:67-74.

© This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/