Search

The type and concentration of charged groups in polymers have a key role in mucoadhesive interactions. A series of cationic poly(amino acid)s with different charge densities was designed to unravel the correlation between chemical structure and mucin-polymer interactions. Colloidal interactions between the mucin protein and synthetic polyaspartamides were tested by dynamic light scattering, zeta potential measurements and turbidimetric titration as a function of polymer-to-mucin mass ratio. The mucoadhesive interactions displayed a strongly non-linear change with polymer composition. The attractive interactions between mucin and the polyaspartamides with at least 50 % cationic groups caused increased light scattering of dispersions due to the aggregation of mucin particles upon their charge reversal. Interactions were further analysed in a thin mucin layer to model life-like situations using a quartz crystal microbalance (QCM) in flow mode. Results pointed out that the fully cationic polyaspartamide is not necessarily superior to derivatives with lower cationic group content. The maximum of adsorbed mass of polymers on mucin was experienced at medium cationic group contents. This emphasizes the relevance of cationic polyaspartamides as mucoadhesive excipients due to their multiple functionalities and the possibility of fine-tuning their interactions with mucin via straightforward chemical steps., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Efficient topical treatment of ocular diseases requires a prolonged residence time of drug formulations. An in situ gelling, mucoadhesive system can provide improved residence time while keeps the installation of the formulation easy and accurate due to its low initial viscosity. We synthesized a two-component, biocompatible water-based liquid formulation showing in situ gelation upon mixing. S-protected, preactivated derivatives of thiolated poly(aspartic acid) (PASP-SS-MNA) were synthesized by coupling the free thiol groups of thiolated poly(aspartic acid) (PASP-SH) with 6-mercaptonicotinic acid (MNA). The amount of protecting groups was 242, 341, and 530 µmol/g depending on the degree of thiolation of PASP. The chemical interaction between PASP-SS-MNA and mucin was proven, indicating the mucoadhesive properties. Disulfide cross-linked hydrogels were formed in situ without an oxidizing agent by mixing the aqueous solutions of PASP-SS-MNA and PASP-SH. The gelation time was controlled between 1 and 6 min, while the storage modulus was as high as 4-16 kPa depending on the composition. Swelling experiments showed that hydrogels with no residual thiol groups are stable in phosphate-buffered saline at pH = 7.4. In contrast, the presence of free thiol groups leads to the dissolution of the hydrogel with a rate depending on the excess of thiol groups. The biological safety of the polymers and MNA was confirmed on Madin-Darby Canine Kidney cell line. Furthermore, a prolonged release of ofloxacin was observed at pH = 7.4 compared to a conventional liquid formulation, supporting the potential of the developed biopolymers in ophthalmic drug delivery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mucoadhesion testing at macroscopic scale needs a robust, convenient in vitro method as ex vivo methods suffer from poor reproducibility and ethical problems. Here we synthesized mucin-free poly(vinyl alcohol) (PVA) and mucin-containing PVA hydrogel substrates (Muc/PVA) to measure adhesion of polymer tablets. Freezing-thawing method was used for gelation to avoid chemical cross-linking and to preserve the functionality of mucin. The adhesion of first generation mucoadhesive polymers, poly(acrylic acid) (PAA) and hydroxypropylmethylcellulose (HPMC) was tested with outstanding reproducibility on individual batches of hydrogels and qualitative agreement with ex vivo literature data. Negatively charged PAA was less adhesive on Muc/PVA surface than on mucin-free PVA whereas HPMC as a neutral polymer displayed similar adhesion strength on both surfaces. Chitosan as a positively charged polymer showed enhanced adhesion on Muc/PVA substrate compared to mucin-free PVA. These results are corroborated by turbidimetric titration which indicated attractive electrostatic interactions between chitosan and mucin in contrast to the lack of attractive interactions for PAA and HPMC. These results prove the role of electronic theory in macroscopic mucoadhesion., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Synthetic polyaspartamides with various functional side groups including primary, secondary, tertiary amine or carboxyl groups were designed to explore the effect of chemical composition on polymer-mucin interactions. Since the molecular weight of the polymers and the degree of modification were identical for each derivative, the role of the functional groups could be evaluated. Chitosan was used as a control sample due to its strong interaction with mucin primarily through electrostatic forces. Mucoadhesive interactions of the polymers with the aqueous dispersion of commercially available porcine gastric mucin were probed on the colloid size scale using various methods including turbidimetric titration, dynamic light scattering and zeta potential measurements. Both the charge of the polymers and the type of amine groups had a pronounced effect on the interactions. The interactions were further analysed by partially screening them with either sodium chloride or urea. The results obtained allow us to classify these polymers in terms of in vitro mucoadhesive strength, which can be useful in the design of mucoadhesive formulations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Poly(aspartic acid) (PASP) derivatives with adjustable pH-dependent solubility were synthesized and characterized to establish the relationship between their structure and solubility in order to predict their applicability as a basic material for enteric coatings. Polysuccinimide, the precursor of PASP, was modified with short chain alkylamines, and the residual succinimide rings were subsequently opened to prepare the corresponding PASP derivatives. Study of the effect of the type and concentration of the side groups on the pH-dependent solubility of PASP showed that solubility can be adjusted by proper selection of the chemical structure. The Henderson-Hasselbalch (HH) and the extended HH equations were used to describe the pH-dependent solubility of the polymers quantitatively. The estimate provided by the HH equation is poor, but an accurate description of the pH-dependent solubility can be found with the extended HH equation. The dissolution rate of a polymer film prepared from a selected PASP derivative was determined by fluorescence marking. The film dissolved rapidly when the pH was increased above its pK a . Cellular viability tests show that PASP derivatives are non-toxic to a human cell line. These polymers are thus of great interest as starting materials for enteric coatings., Statement of Significance: Poly(amino acid) type biocompatible polymers were synthesized for future use as pharmaceutical film coatings. To this end, we tailored the pH-dependent solubility of poly(aspartic acid) (PASP). It was found that both the solubility and the pK a values of the modified PASP depended strongly on composition. Fluorescent marking was used to characterize the dissolution of a chosen PASP derivative. In acidic media only a negligible amount of the polymer dissolved, but dissolution was very fast and complete at the pH values that prevail in the small intestine. As a consequence, enteric coatings based on such PASP derivatives may be used for drug delivery in the gastrointestinal tract., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Chemically cross-linked poly(aspartic acid) (PASP) gels were prepared by a solid-liquid phase separation technique, cryogelation, to achieve a supermacroporous interconnected pore structure. The precursor polymer of PASP, polysuccinimide (PSI) was cross-linked below the freezing point of the solvent and the forming crystals acted as templates for the pores. Dimethyl sulfoxide was chosen as solvent instead of the more commonly used water. Thus larger temperatures could be utilized for the preparation and the drawback of increase in specific volume of water upon freezing could be eliminated. The morphology of the hydrogels was characterized by scanning electron microscopy and interconnectivity of the pores was proven by the small flow resistance of the gels. Compression tests also confirmed the interconnected porous structure and the complete re-swelling and shape recovery of the supermacroporous PASP hydrogels. The prepared hydrogels are of interest for several biomedical applications as scaffolding materials because of their cytocompatibility, controllable morphology and pH-responsive character., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Chemically cross-linked poly(aspartic acid) (PASP) gels were prepared by the hydrolysis of poly(succinimide) (PSI). The latter was prepared by thermal polycondensation of aspartic acid. The PSI chains were cross-linked by natural amines and amino acid derivatives such as putrescin, spermine, spermidine, lysine and cystamine to obtain biodegradable, biocompatible, amino acid-based hydrogels. The volume of the synthesized unhydrolyzed PSI gels changes abruptly at a well-defined pH that results in ring opening, while the hydrolyzed gels show a volume phase transition around the pK values of PASP. The unidirectional stress-strain behavior of the gels as well as the dependence of equilibrium swelling degree on the pH was carefully studied and the most important network parameters were determined by a modified version of the Brannon-Peppas-Peppas theory.