(M1530-04-20) Polymer Effects on Kolliphor P407's Mucoadhesion

Purpose: The poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, known as poloxamer (Pluronic®), are unique thermoresponsive amphiphilic polymers with many pharmaceutical and biomedical applications such as the development of drug delivery systems[1]. Though widely exploited in the healthcare sector, their use in clinical settings have been limited because they may either gel above or below the body temperature or possess poor mechanical properties [2]. The mechanical characteristics of Poloxamer gels can be modified by blending Poloxamers with other polymers, creating hybrid systems with tailored properties. The choice of polymer blends can influence parameters such as gel strength, elasticity, and adhesiveness, providing versatility in various applications[3]. Natural and synthetic polymers that could serve this purpose include chitosan, alginates, polyvinyl alcohol, poly(ethylene glycol), and poly(acrylic acid) derivatives like Carbopol. This investigation aimed to evaluate the effect of various polymer blends on mucoadhesive properties of Kolliphor® P 407 Geismer solutions.

Methods: Different Kolliphor P 407 Geismer concentrations were prepared using the cold method with deionized water as solvent. The different polymer blends containing 0.5% of Carbopol, Chitosan, Sodium Alginate, and Sodium carboxymethylcellulose were also prepared and stored in a refrigerator overnight. For the mucoadhesion tests, a Brookfield CT3-1000 Texture Analyzer equipped with an acrylic probe, a 1 Kg loading cell, and a TA-RT Kit was utilized. Mucin discs were affixed to the bottom of the acrylic probe, which was then lowered onto the surface of the gelled samples at a rate of 0.5 mm/sec, maintaining contact for 30 seconds. The maximum negative detachment force necessary to separate the mucin disc from the gel surface was measured, representing the adhesion force and adhesiveness. Additionally, the resilience was recorded.

Results: The adhesive forces (N) for the Kolliphor P407 Geismer solutions at concentrations of 20%, 17.5%, 15%, and 12.5% were 1.021±0.01, 0.852±0.02, 0.667±0.02, and 0.076±0.01, respectively. The adhesiveness (mJ) for the same concentrations were 2.27±0.03, 1.92±0.04, 1.51±0.02, and 0.35±0.02, respectively. Resilience values were 0.04±0.00 for the 20% solution, and 0.02±0.00 for the 17.5%, 15%, and 12.5% solutions. The adhesive forces (N) for the 0.5% Carbopol-Kolliphor P407 Geismer mixtures at concentrations of 20%, 17.5%, 15%, and 12.5% were 1.326±0.01, 1.107±0.01, 0.789±0.02, and 0.106±0.02, respectively. The adhesiveness (mJ) for these mixtures were 3.41±0.02, 2.98±0.01, 2.29±0.03, and 0.60±0.03, respectively. A resilience of 0.04±0.00 was recorded for all Carbopol-Kolliphor P407 mixtures. For the 0.5% Sodium Alginate-Kolliphor P407 Geismer mixtures, the adhesive forces (N) at 20%, 17.5%, 15%, and 12.5% concentrations were 0.7623±0.02, 0.6361±0.01, 0.489±0.03, and 0.0608±0.02, respectively. The adhesiveness (mJ) for these mixtures were 4.387±0.02, 3.72±0.02, 2.96±0.01, and 1.23±0.01, respectively. A resilience of 0.04±0.00 was recorded for all Sodium Alginate-Kolliphor P407 mixtures. The adhesive forces (N) for the 0.5% Chitosan-Kolliphor P407 Geismer mixtures at 20%, 17.5%, 15%, and 12.5% concentrations were 0.6324±0.02, 0.5277±0.02, 0.378±0.02, and 0.066±0.02, respectively. The adhesiveness (mJ) for these mixtures were 5.235±0.03, 4.42±0.02, 3.47±0.03, and 1.92±0.02, respectively. A resilience of 0.04±0.00 was recorded for all Chitosan-Kolliphor P407 mixtures. For the 0.5% Sodium Carboxymethylcellulose-Kolliphor P407 Geismer mixtures, the adhesive forces (N) at 20%, 17.5%, 15%, and 12.5% concentrations were 0.746±0.01, 0.623±0.02, 0.426±0.01, and 0.076±0.01, respectively. The adhesiveness (mJ) for these mixtures were 5.2120±0.02, 4.40±0.03, 3.49±0.03, and 1.83±0.03, respectively. A resilience of 0.04±0.00 was recorded for all Sodium Carboxymethylcellulose-Kolliphor P407 mixtures. The method employed in this study effectively utilized the cold method to prepare various concentrations of Kolliphor P 407 Geismer solutions, along with polymer blends incorporating Carbopol, Chitosan, Sodium Alginate, and Sodium carboxymethylcellulose. The mucoadhesion tests, conducted using a Brookfield CT3-1000 Texture Analyzer, provided detailed insights into the adhesive and resilience properties of these mixtures. The results showed a clear trend: as the concentration of Kolliphor P 407 Geismer decreased, both the adhesive force and adhesiveness similarly diminished across all polymer blends. Interestingly, the resilience values remained consistent, indicating that the mechanical recovery of the gelled samples post-adhesion was not significantly impacted by the concentration variations. These consistent resilience values suggest that the structural integrity of the gels was maintained, regardless of polymer concentration, highlighting the robust nature of these formulations.

Conclusion: The adhesive force data indicates that blending poloxamer (P407) with other polymers significantly enhances its mucoadhesive properties. Among the tested polymers, Carbopol demonstrated the most effective enhancement of adhesive force, followed by Sodium Alginate and Sodium Carboxymethylcellulose. Chitosan, while effective, showed the least enhancement in adhesive force. Regarding adhesiveness, blending poloxamer (P407) with other polymers significantly improved its adhesive properties. Chitosan and Sodium Carboxymethylcellulose were the most effective in increasing adhesiveness, followed closely by Sodium Alginate and then Carbopol. These findings are essential for optimizing poloxamer-based formulations for applications requiring varying degrees of mucoadhesion.

References: 1. Mfoafo, K., et al., Contemporary Applications of thermogelling PEO-PPO-PEO triblock copolymers. Journal of Drug Delivery Science and Technology, 2022: p. 103182.
2. Sosnik, A., et al., Crosslinkable PEO-PPO-PEO-based reverse thermo-responsive gels as potentially injectable materials. Journal of Biomaterials Science, Polymer Edition, 2003. 14(3): p. 227-239.
3. Jones, D.S., et al., Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity. International journal of pharmaceutics, 2009. 372(1-2): p. 49-58.

Acknowledgements: Acknowledge BASF for providing Kolliphor P407 Samples for the Research

A graph showing the mean ± SD adhesive forces of different Kolliphor P407 - Polymer combinations.



A graph showing the mean ± SD adhesiveness of different Kolliphor P407 - Polymer combinations

Set-up for the mucoadhesion tests