Unveiling the potential of biomaterials and their synergistic fusion in tissue engineering.

Inspired by nature, tissue engineering aims to employ intricate mechanisms for advanced clinical interventions, unlocking inherent biological potential and propelling medical breakthroughs. Therefore, medical, and pharmaceutical fields are growing interest in tissue and organ replacement, repair, and regeneration by this technology. Three primary mechanisms are currently used in tissue engineering: transplantation of cells (I), injection of growth factors (II) and cellular seeding in scaffolds (III). However, to develop scaffolds presenting highest potential, reinforcement with polymeric materials is growing interest. For instance, natural and synthetic polymers can be used. Regardless, chitosan and keratin are two biopolymers presenting great biocompatibility, biodegradability and non-antigenic properties for tissue engineering purposes offering restoration and revitalization. Therefore, combination of chitosan and keratin has been studied and results exhibit highly porous scaffolds providing optimal environment for tissue cultivation. This review aims to give an historical as well as current overview of tissue engineering, presenting mechanisms used and polymers involved in the field.

Phosphatase-degradable nanoparticles providing sustained drug release.

AIM: The study aimed to develop enzyme-degradable nanoparticles comprising polyphosphates and metal cations providing sustained release of the antibacterial drug ethacridine (ETH). METHODS: Calcium polyphosphate (Ca-PP), zinc polyphosphate (Zn-PP) and iron polyphosphate nanoparticles (Fe-PP NPs) were prepared by co-precipitation of sodium polyphosphate with cations and ETH. Developed nanocarriers were characterized regarding particle size, PDI, zeta potential, encapsulation efficiency and drug loading. Toxicological profile of nanocarriers was assessed via hemolysis assay and cell viability on human blood erythrocytes and HEK-293 cells, respectively. The enzymatic degradation of NPs was evaluated in presence of alkaline phosphatase (ALP) monitoring the release of monophosphate, shift in zeta potential and particle size as well as drug release. The antibacterial efficacy against Escherichia coli was determined via microdilution assay. RESULTS: NPs were obtained in a size range between 300 - 480 nm displaying negative zeta potential values. Encapsulation efficiency was in the range of 83.73 %- 95.99 %. Hemolysis assay underlined sufficient compatibility of NPs with blood cells, whereas drug and NPs showed a concentration dependent effect on HEK-293 cells viability. Ca- and Zn-PP NPs exhibited remarkable changes in zeta potential, particle size, monophosphate and drug release upon incubation with ALP, compared to Fe-PP NPs showing only minor differences. The released ETH from Ca- and Zn-PP nanocarriers retained the antibacterial activity against E. coli, whereas no antibacterial effect was observed with Fe-PP NPs. CONCLUSION: Polyphosphate nanoparticles cross-linked with divalent cations and ETH hold promise for sustained drug delivery triggered by ALP for parental administration.

Counterion optimization for hydrophobic ion pairing (HIP): Unraveling the key factors.

In the present study, various surfactants were combined with insulin (INS), bovine serum albumin (BSA) and horseradish peroxidase (HRP) via hydrophobic ion pairing to increase lipophilicity and facilitate incorporation into self-emulsifying drug delivery systems (SEDDS). Lipophilicity of model proteins was successfully increased, achieving log Dn-butanol/water values up to 3.5 (INS), 3.2 (BSA) and 1.2 (HRP). Hereby, key factors responsible for complex formation were identified. In particular, surfactants with branched alkyl chains or chain lengths greater than C12 showed favorable properties for hydrophobic ion pairs (HIP). Furthermore, flexibility of the carbon chain resulted in higher lipophilicity and suitability of polar head groups of surfactants for HIP decreased in the rank order sulfonate > sulfosuccinate > phosphate = sulfate > carbonate > phosphonic acids = sulfobetaines. Stability studies of formed HIP complexes were performed in various gastrointestinal fluids and their solubility was determined in commonly used SEDDS excipients. Formed complexes were stable in simulated gastrointestinal fluids and could be incorporated into SEDDS formulations (C1: 10% caprylocaproyl polyoxyl-8 glycerides, 20% PEG-40 hydrogenated castor oil, 20% medium-chain triglycerides, 50% n-butanol; C2: 10% caprylocaproyl polyoxyl-8 glycerides, 20% PEG-40 hydrogenated castor oil, 20% medium-chain triglycerides, 40% n-butanol, 10% 1,2-butanediol), resulting in suitable payloads of up to 11.9 mg/ml for INS, 1.0 mg/ml for BSA and 1.6 mg/ml for HRP.

Charge-reversal nanoemulsions: A systematic investigation of phosphorylated PEG-based surfactants.

Surfactants bearing monophosphate esters with PEG of increasing chain length and different lipophilic tail structures were investigated to improve the effectiveness of enzyme triggered charge-converting nanoemulsions. The surfactants PEG-8-stearate, PEG-22-tocopheryl succinate (TPGS), PEG-3-oleate, PEG-9-oleate and PEG-9-lauryl ether were phosphorylated and incorporated in a self-emulsifying drug delivery system (SEDDS) exhibiting a defined PEG corona. To provide a positive zeta potential increasing amounts of the cationic surfactant benzalkonium chloride (BA) were incorporated. The effect of these PEG monophosphate esters (P-PEG-surfactants) was evaluated based on enzyme induced phosphate release and change in zeta potential. Significant enzyme induced charge conversion was observed for all P-PEG-surfactants, showing shifts from Δ3 mV to Δ31 mV. Surfactants comprising the shortest and longest PEG chain showed similar amplitudes (P-PEG-3-oleate: Δ11.9 mV; P-PEG-22-TPGS Δ10.2 mV), whereas P-PEG-8-stearate, P-PEG-9-oleate and P-PEG-9-lauryl ether bearing similarly long PEG chains but different lipophilic tail structures resulted in pronounced differences in amplitudes of Δ10.3 mV, Δ14.5 mV and Δ18.1 mV, respectively. Furthermore, an indirect correlation between the lipophilicity of P-PEG-surfactants and the obtained charge-reversing effect was observed. With the exception of P-PEG-lauryl ether, this charge-reversal effect decreased with increasing BA concentrations. In conclusion, the enzyme induced amplitude of charge conversion of P-PEG-surfactants depends to a high extent on their lipophilic tail structure. Based on this knowledge potent charge-reversal nanoemulsions can be designed.

Thiolated Nanoparticles for Biomedical Applications: Mimicking the Workhorses of Our Body.

Advances in nanotechnology have generated a broad range of nanoparticles (NPs) for numerous biomedical applications. Among the various properties of NPs are functionalities being related to thiol substructures. Numerous biological processes that are mediated by cysteine or cystine subunits of proteins representing the workhorses of the bodies can be transferred to NPs. This review focuses on the interface between thiol chemistry and NPs. Pros and cons of different techniques for thiolation of NPs are discussed. Furthermore, the various functionalities gained by thiolation are highlighted. These include overall bio- and mucoadhesive, cellular uptake enhancing, and permeation enhancing properties. Drugs being either covalently attached to thiolated NPs via disulfide bonds or being entrapped in thiolated polymeric NPs that are stabilized via inter- and intrachain crosslinking can be released at the diseased tissue or in target cells under reducing conditions. Moreover, drugs, targeting ligands, biological analytes, and enzymes bearing thiol substructures can be immobilized on noble metal NPs and quantum dots for therapeutic, theranostic, diagnostic, biosensing, and analytical reasons. Within this review a concise summary and analysis of the current knowledge, future directions, and potential clinical use of thiolated NPs are provided.