Is hyaluronic acid the perfect excipient for the pharmaceutical need?

Hyaluronic acid has become an interesting and important polymer as an excipient for pharmaceutical products due to its beneficial properties, like solubility, biocompatibility and biodegradation. To improve the properties of hyaluronic acid, different possibilities for chemical modifications are presented, and the opportunities as novel systems for drug delivery are discussed. This review gives an overview over the production of hyaluronic acid, the possibilities of its chemical modification and the current state of in vitro and in vivo research.

A gellan gum derivative as in-situ gelling cationic polymer for nasal drug delivery.

The aim of the present study was the development of a novel gellan gum derivative exhibiting mucoadhesive properties for nasal application. Accomplishing this, amino groups have been introduced to the polymeric backbone. The resulting synthesis products were characterized in terms of the amount of attached amino groups, regarding hydration, zeta potential and gel characteristics.

Zeta potential changing nanoemulsions: Impact of PEG-corona on phosphate cleavage.

The aim of this study was to evaluate the impact of a PEG-corona on oily droplets of a nanoemulsion on phosphate cleavage on their surface. A PEG-free nanoemulsion composed of 60% oleic acid, 30% Capmul MCM EP and 10% Span 85 being additionally stabilized by 1% cetyltrimethylammonium bromide (CTAB) and 3% phosphatidic acid (PA) was evaluated regarding phosphate release, zeta potential change and mucus permeation properties. In order to evaluate the impact of PEG-corona on phosphate release 10%, 20% and 30% of polyethoxylated-35 castor oil were incorporated in the nanoemulsion.

Diaminated Starch: A Competitor of Chitosan with Highly Mucoadhesive Properties due to Increased Local Cationic Charge Density.

The purpose of this study was to synthesize diaminated starch as a novel mucoadhesive polymer. Starch was tosylated and then reacted with ethylenediamine. The degree of amination was determined by 2,4,6-trinitrobenzene sulfonic acid assay.

Intestinal enzyme delivery: Chitosan/tripolyphosphate nanoparticles providing a targeted release behind the mucus gel barrier.

Aim: The aim of this study was to evaluate the potential of chitosan/tripolyphosphate (TPP) nanoparticles to provide a targeted release of β-galactosidase behind the intestinal mucus gel barrier.

Methods: Nanoparticles were prepared by ionic gelation of chitosan and TPP in the presence of β-galactosidase. Particles were characterized regarding size, polydispersity index and drug load.

Cationic starch derivatives as mucoadhesive and soluble excipients in drug delivery.

The aim of this study was to develop a novel mucoadhesive cationic polymer by introducing primary amino groups to the polymeric backbone of starch. This newly synthesized polymer should exhibit superior properties over chitosan regarding solubility, mucoadhesiveness and cytotoxicity. Increasing amounts of sodium periodate were used to cleave and oxidize vicinal diols under aldehyde formation obtaining three different degrees of modification.

Self-emulsifying drug delivery systems: In vivo evaluation of their potential for oral vaccination.

Oral Immunization remains a challenge as antigens are rapidly metabolized in the gastrointestinal tract. In numerous previous studies, Self-emulsifying drug delivery systems (SEDDS) have demonstrated to be a promising tool for oral delivery of biologics. In this study, the potential of SEDDS as vehicle for oral vaccination has been evaluated.

In Vitro-in Vivo Correlation of Mucoadhesion Studies on Buccal Mucosa.

Background: For the development of novel buccoadhesive formulations, their physicochemical properties, strength of the interfacial joint, and residence time on the buccal mucosa are considered as a measure for their in vivo mucoadhesive properties. Focusing on these parameters, the predictive power of established in vitro systems was assessed for mucoadhesive properties in humans using discs as the model solid dosage form.

Methods: Compressed into discs, hydroxyethyl cellulose, carboxymethyl cellulose, carbopol, polycarbophil, alginate, and xanthan gum were used as model polymers.

Thiolated polymers: Bioinspired polymers utilizing one of the most important bridging structures in nature.

Thiolated polymers designated "thiomers" are obtained by covalent attachment of thiol functionalities on the polymeric backbone of polymers. In 1998 these polymers were first described as mucoadhesive and in situ gelling compounds forming disulfide bonds with cysteine-rich substructures of mucus glycoproteins and crosslinking through inter- and intrachain disulfide bond formation. In the following, it was shown that thiomers are able to form disulfides with keratins and membrane-associated proteins exhibiting also cysteine-rich substructures.

Covalently binding mucoadhesive polymers: N-hydroxysuccinimide grafted polyacrylates.

Aim: The aim of the study was to establish a novel type of covalently mucus-binding polymers by targeting selectively amino groups within mucus glycoproteins.

Methods: N-Hydroxysuccinimide (NHS) was attached to carboxylic groups of polyacrylic acid (PAA). The reaction was mediated by the coupling reagent N,N'-dicyclohexylcarbodiimide (DCC) achieving polymeric NHS esters being able to form amide bonds with free amino groups.

In vitro evaluation of a self-emulsifying drug delivery system (SEDDS) for nasal administration of dimenhydrinate.

The objective of the study was the development and in vitro characterization of a self-emulsifying drug delivery system (SEDDS) for the nasal application of dimenhydrinate. Final composition of SEDDS was established based on drug solubility and stability studies. Dimenhydrinate was loaded into the SEDDS pre-concentrates to 7.

Chitosan: The One and Only? Aminated Cellulose as an Innovative Option for Primary Amino Groups Containing Polymers.

The aim of this study was the synthesis and in vitro characterization of aminated cellulose as alternative excipient to chitosan. The aldehyde form of cellulose was generated via the oxidative cleavage of vicinal diols by the addition of increasing concentrations of sodium periodate. The insertion of primary amines was achieved by reductive amination with ammonia.

Non-ionic thiolated cyclodextrins - the next generation.

Introduction: The current study was aimed at developing a novel mucoadhesive thiolated cyclodextrin (CD) without ionizable groups and an intact ring backbone for drug delivery.

Materials And Methods: Thiolated beta CD (β-CD) was prepared through bromine substitution of its hydroxyl groups followed by replacement to thiol groups using thiourea. The thiolated β-CD was characterized in vitro via dissolution studies, cytotoxicity studies, mucoadhesion studies on freshly excised porcine intestinal mucosa, and inclusion complex formation with miconazole nitrate.

New perspectives of starch: Synthesis and in vitro assessment of novel thiolated mucoadhesive derivatives.

Aim: The purpose of this study was to develop a novel thiolated starch polymer with improved mucoadhesive properties by conjugation of cysteamine to starch as a natural polymer of restricted mucoadhesive properties.

Methods: Aldehyde substructures were integrated into starch via oxidative cleavage of vicinal diols by increasing amounts of sodium periodate followed by covalent attachment of cysteamine to oxidized starch via reductive amination. Thiol groups were quantified via Ellman's reaction and their impact on mucoadhesion was analyzed by rheological investigations, the rotating cylinder method and tensile studies on porcine mucosa.

Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs.

Unlabelled: The objective of this study was to investigate the impact of different hydrophobic ion pairs (HIP) on the oral bioavailability of the model drug octreotide in pigs. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate and docusate differing in lipophilicity. These hydrophobic ion pairs were incorporated in self-emulsifying drug delivery systems (SEDDS) based on BrijO10, octyldodecanol, propylene glycol and ethanol in a concentration of 5mg/ml.

Nasal drug delivery: Design of a novel mucoadhesive and in situ gelling polymer.

The aim of the present study was to establish a novel polymeric excipient for liquid nasal dosage forms exhibiting viscosity increasing properties, improved mucoadhesion and stability towards oxidation in solution. In order to achieve this goal, 2-mercaptonicotinic acid was first coupled to l-cysteine by disulfide exchange reaction and after purification directly attached to the polymeric backbone of xanthan gum by carbodiimide mediated amide bond formation. The resulting conjugate was characterized with respect to the amount of coupled ligand, the in situ gelling behavior, mucoadhesive properties and stability towards oxidation.

Charge changing phosphorylated polymers: Proof of in situ mucoadhesive properties.

The objective of this study was to design a novel polyethylene glycol (PEG) derivative exhibiting mucus permeating and mucoadhesive properties. Therefore, the enzymatically degradable phosphate ester, phosphotyrosine (Ptyr) was covalently attached to PEG-diamine. The synthesized PEG-Ptyr was studied in terms of enzymatic degradability on Caco 2 cells and by isolated intestinal alkaline phosphatase (IAP).

2,2'Dithiodinicotinyl ligands: Key to more reactive thiomers.

The aim of this study was to establish a novel type of preactivated thiomers exhibiting a comparatively higher reactivity with mucus and consequently improved mucoadhesive properties. In order to achieve this goal, the dimeric form of 2-mercaptonicotinic acid (MNA-MNA) was directly attached to the polymeric backbone of chitosan (CHI) via amide bond formation mediated by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) used as a coupling reagent. The remaining free amino groups were in the following reacted with succinic anhydride (Succ) in order to obtain a uniformly anionically charged polymer (CHI-Succ-MNA-MNA).

Zeta potential changing phosphorylated nanocomplexes for pDNA delivery.

The objective of this study was to evaluate the suitability of a zeta potential changing system as gene delivery system. The phosphate ester bearing ligand 6-phosphogluconic acid (6-PGA) was attached to linear and branched polyethyleneimine (PEI) via a carbodiimide-mediated reaction whereby 287 μmol and 413 μmol 6-PGA could be coupled per gram polymer. Nanocomplexes of these modified polymers with pDNA showed a zeta potential of +12 mV for nanocomplexes with the linear PEI-6PGA and +16 mV in case of the branched derivative.