Biocompatible Alternatives Research Articles

Site-Selective Zwitterionic Poly(caprolactone-carboxybetaine)-Growth Hormone Receptor Antagonist Conjugate: Synthesis and Biological Evaluation.

Zwitterionic polymers have been found to be biocompatible alternatives to poly(ethylene glycol) (PEG) for conjugation to proteins. This work reports the site-selective conjugation of poly(caprolactone-carboxybetaine) (pCLZ) to human growth hormone receptor antagonist (GHA) B2036-alkyne and investigation of safety, activity, and pharmacokinetics. Azide-end-functionalized pCLZs were synthesized and conjugated to GHA B2036-alkyne via copper-catalyzed click reaction. The resulting inhibitory bioactivity concentration responses in Ba/F3-GHR cells were compared to those of PEGylated GHA B2036. IgG and IgM antibody production was tested in mice, and no measurable antibody or cytokine production was detected for the pCLZ conjugate. Using 18F-labeled PET/CT imaging, the pCLZ conjugate showed an increase in circulation time compared to that of GHA B2036. Acute toxicity of the polymer was investigated in vivo and found to be nontoxic. Ex vivo degradation of the polymer on the conjugate was investigated. The results suggest that pCLZ-GHA is a potentially safe alternative to PEG-GHA.

Milk-Based Ointment Accelerates Wound Healing: A Comparative Study in Rabbits

Background: Wound healing is a multi-stage process that restores tissue integrity following injury. While chemical treatments like phenytoin aid in healing, traditional remedies, such as milk-based applications, remain underexplored. Milk, particularly its proteins, is known for promoting tissue repair and collagen synthesis. This study evaluated the wound-healing efficacy of a milk-based ointment (MO) on open skin wounds in rabbits. Methods: Male New Zealand white rabbits were randomly assigned to six groups, including negative controls, placebo (eucerin), and 1% phenytoin, alongside three MO groups (2%, 5%, 10% concentrations). The treatments were applied twice daily for 14 days. Wound healing was assessed through macroscopic analysis, tensile strength measurement, hydroxyproline levels, and histological examination. Results: The 5% MO-treated group exhibited the fastest wound healing, achieving full closure in 15 days, outperforming both controls and the phenytoin-treated group (17 days). Hydroxyproline levels and tensile strength were significantly higher in the 5% MO group, indicating enhanced collagen production and stronger tissue regeneration. Histological analysis further confirmed accelerated epithelialization and granulation in MO-treated groups. Conclusion: The study demonstrated that milk-based ointments, particularly at a 5% concentration, significantly enhance wound healing, suggesting their potential as cost-effective, biocompatible alternatives to conventional chemical treatments like phenytoin. Further research is needed to explore clinical applications in humans.

Mangostanin hyaluronic acid hydrogel as an effective biocompatible alternative to chlorhexidine

Periodontal disease (PD) prevention and treatment products typically demonstrate excellent antibacterial activity, but recent studies have raised concerns about their toxicity on oral tissues. Therefore, finding a biocompatible alternative that retains antimicrobial properties is imperative. In this study, a chemically modified hyaluronic acid (HA) hydrogel containing mangostanin (MGTN) was developed. Native HA was chemically modified, incorporating amino and aldehyde groups in different batches of HA, allowing spontaneous crosslinking and gelation when combined at room temperature. MGTN at different concentrations was incorporated before gelation. The structure, swelling characteristics MGTN release, rheological parameters, and in vitro degradation performance of the loaded hydrogel were first evaluated in the study. Then, antimicrobial properties were tested on Porphyromonas gingivalis and its biocompatibility in 3D-engineered human gingiva. HA hydrogel was very stable and showed a sustained release for MGTN for at least 7 days. MGTN-loaded HA hydrogel showed equivalent antimicrobial activity compared to a commercial gel of HA containing 0.2 % chlorhexidine (CHX). In contrast, while MGTN HA hydrogel was biocompatible, CHX gel showed high cytotoxicity, causing cell death and tissue damage. Modified HA hydrogel allows controlled release of MGTN, resulting in a highly biocompatible hydrogel with antibacterial properties. This hydrogel is a suitable alternative therapy to prevent and treat PD.

Development of New Composite Materials by Modifying the Surface of Porous Hydroxyapatite Using Cucurbit[n]urils.

This study represents an advancement in the field of composite material engineering, focusing on the synthesis of composite materials derived from porous hydroxyapatite via surface modification employing cucurbit[n]urils, which are highly promising macrocyclic compounds. The surface modification procedure entailed the application of cucurbit[n]urils in an aqueous medium onto the hydroxyapatite surface. A comprehensive characterization of the resulting materials was undertaken, employing analytical techniques including infrared (IR) spectroscopy and scanning electron microscopy (SEM). Subsequently, the materials were subjected to rigorous evaluation for their hemolytic effect, anti-inflammatory properties, and cytotoxicity. Remarkably, the findings revealed a notable absence of typical hemolytic effects in materials incorporating surface-bound cucurbit[n]urils. This observation underscores the potential of these modified materials as biocompatible alternatives. Notably, this discovery presents a promising avenue for the fabrication of resilient and efficient biocomposites, offering a viable alternative to conventional approaches. Furthermore, these findings hint at the prospect of employing supramolecular strategies involving encapsulated cucurbit[n]urils in analogous processes. This suggests a novel direction for further research, potentially unlocking new frontiers in material engineering through the exploitation of supramolecular interactions.

Studies of Potential Migration of Hazardous Chemicals from Sustainable Food Contact Materials.

In recent years, due to modern techniques for the distribution, transport, and retail sale of food, the production of large amounts of non-biodegradable and bioaccumulative packaging waste has become a major environmental issue. To address this issue, new food packaging materials based on renewable biomass have been studied as eco-friendly, biodegradable, and biocompatible alternatives to synthetic materials. However, although these materials are not petrochemical derivatives, the presence of contaminants cannot be excluded. This work aims to extend the knowledge on bio-based packaging materials, researching the presence of contaminants potentially able to migrate to food at concentrations of concern. In this study, we focus on two classes of contaminants, organophosphate esters (OPEs) and perfluoroalkyl substances (PFASs), carrying out migration tests toward different simulants, according to the current European regulation. PFAS analysis was performed using high-resolution liquid chromatography coupled to ion trap-tandem mass spectrometry (QTrap). OPE analyses were performed both by gas chromatography-mass spectrometry (GC-MS) and high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (TQMS). Preliminary findings demonstrate the release of toxic OPEs and PFASs from bio-based food packaging, highlighting the need to investigate the presence of potentially harmful chemicals in these materials.

Chemotherapeutics-Loaded Poly(Dopamine) Core-Shell Nanoparticles for Breast Cancer Treatment.

Chemophotothermal therapy is an emerging treatment of metastatic and drug-resistant cancer anomalies. Among various photothermal agents tested, poly(dopamine) provides an excellent biocompatible alternative that can be used to develop novel drug delivery carriers for cancer treatment. This study explores the synthesis of starch-encapsulated, poly(dopamine)-coated core-shell nanoparticles in a one-pot synthesis approach and by surfactant-free approach. The nanoparticles produced are embellished with polymeric stealth coatings and are tested for their physiologic stability, photothermal properties, and drug delivery in metastatic triple-negative breast cancer cell (TNBC) lines. Our results indicate that stealth polymer-coated nanoparticles exhibit superior colloidal stability under physiologic conditions, and are excellent photothermal agents, as determined by the increase in temperature of solution in the presence of nanoparticles, upon laser irradiation. The chemotherapeutic drug-loaded nanoparticles also showed concentration-dependent toxicities in TNBC and in a brain metastatic cell line. SIGNIFICANCE STATEMENT: This study develops, for the first time, biocompatible core-shell nanoparticles in a template-free approach that can serve as a drug delivery carrier and as photothermal agents for cancer treatment.

Elevated fucose content enhances the cryoprotective performance of anionic polysaccharides

Biological cryopreservation often involves using a cryoprotective agent (CPA) to mitigate lethal physical stressors cells endure during freezing and thawing, but effective CPA concentrations are cytotoxic. Hence, natural polysaccharides have been studied as biocompatible alternatives. Here, a subset of 26 natural polysaccharides of various chemical composition was probed for their potential in enhancing the metabolic post-thaw viability (PTV) of cryopreserved Vero cells. The best performing cryoprotective polysaccharides contained significant fucose amounts, resulting in average PTV 2.8-fold (up to 3.1-fold) compared to 0.8-fold and 2.2-fold for all non-cryoprotective and cryoprotective polysaccharides, respectively, outperforming the optimized commercial CryoStor™ CS5 formulation (2.6-fold). Stoichiometrically, a balance between fucose (18–35.7 mol%), uronic acids (UA) (13.5–26 mol%) and high molecular weight (MW > 1 MDa) generated optimal PTV. Principal component analysis (PCA) revealed that fucose enhances cell survival by a charge-independent, MW-scaling mechanism (PC1), drastically different from the charge-dominated ice growth disruption of UA (PC2). Its neutral nature and unique properties distinguishable from other neutral monomers suggest fucose may play a passive role in conformational adaptability of polysaccharide to ice growth inhibition, or an active role in cell membrane stabilization through binding. Ultimately, fucose-rich anionic polysaccharides may indulge in polymer-ice and polymer-cell interactions that actively disrupt ice and minimize lethal volumetric fluctuations due to a balanced hydrophobic-hydrophilic character. Our research showed the critical role neutral fucose plays in enhancing cellular cryopreservation outcomes, disputing previous assumptions of polyanionicity being the sole governing predictor of cryoprotection.

Gastric stability of bare and chitosan-fabricated ferritin and its bio-mineral: implication for potential dietary iron supplements.

Iron deficiency anaemia (IDA), the most widespread nutritional disorder, is a persistent global health issue affecting millions, especially in resource-limited geographies. Oral iron supplementation is usually the first choice for exogenous iron administration owing to its convenience, effectiveness and low cost. However, commercially available iron supplementations are often associated with oxidative stress, gastrointestinal side effects, infections and solubility issues. Herein, we aim to address these limitations by employing ferritin proteins-self-assembled nanocaged architectures functioning as a soluble cellular iron repository-as a non-toxic and biocompatible alternative. Our in vitro studies based on PAGE and TEM indicate that bare ferritin proteins are resistant to gastric conditions but their cage integrity is compromised under longer incubation periods and at higher concentrations of pepsin, which is a critical component of gastric juice. To ensure the safe delivery of encapsulated iron cargo, with minimal cage disintegration/degradation and iron leakage along the gastrointestinal tract, we fabricated the surface of ferritin with chitosan. Further, the stoichiometry and absorptivity of iron-chelator complexes at both gastric and circumneutral pH were estimated using Job's plot. Unlike bipyridyl, deferiprone exhibited pH dependency. In vitro kinetics was studied to evaluate iron release from bare and chitosan-fabricated ferritins employing both reductive (in the presence of ascorbate and bipyridyl) and non-reductive (direct chelation by deferiprone) pathways to determine their bio-mineral stabilities. Chitosan-decorated ferritin displayed superior cage integrity and iron retention capability over bare ferritin in simulated gastric fluid. The ability of ferritins to naturally facilitate controlled iron release in conjugation with enteric coating provided by chitosan may mitigate the aforementioned side effects and enhance iron absorption in the intestine. The results of the current study could pave the way for the development of an oral formulation based on ferritin-caged iron bio-mineral that can be a promising alternative for the treatment of IDA, offering better therapeutic outcomes.

Hyaluronic acid/polyphenol sunscreens with broad-spectrum UV protection properties from tannic acid and quercetin

Currently, commercial sunscreens cause a number of biotoxicity and environmental issues, making it imperative to develop biocompatible alternatives. In this study, we aimed to develop an alternative sunscreen from two ecofriendly and biocompatible natural polyphenolic compounds, tannic acid (TA) and quercetin (Que). The sunscreen was prepared through a simple process using an oil-in-water emulsion as the medium and hyaluronic acid (HA) as the base polymer to improve biocompatibility. The HA/TA/Que. sunscreen prepared in this study exhibits 0 % transmittance in the UVB region and <15 % transmittance in the UVA region, resulting in excellent sun-protection properties (SPF 30). Remarkably, the as-prepared HA/TA/Que. sunscreen has a suitable viscosity and similar UV protection properties to those of commercial sunscreens. The HA/TA/Que. sunscreen also exhibits 90.4 % antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl, demonstrating an ability to effectively capture reactive oxygen species that directly affect the skin. In addition, the cell viability was >90 % at a concentration of 50 μg/mL after 7 days, indicating excellent cytocompatibility. Owing to its various advantageous features, the HA/TA/Que. sunscreen with excellent sun protection properties and multiple functionalities is expected to resolve many environmental and biological issues caused by commercial sunscreens.

Structural Variations in Carboxylated Bispidine Ligands: Influence of Positional Isomerism and Rigidity on the Conformation, Stability, Inertness and Relaxivity of their Mn2+ Complexes.

Mn2+ complexes of 2,4-pyridyl-disubstituted bispidine ligands have emerged as more biocompatible alternatives to Gd3+-based MRI probes. They display relaxivities comparable to that of commercial contrast agents and high kinetic inertness, unprecedented for Mn2+ complexes. The chemical structure, in particular the substituents on the two macrocyclic nitrogens N3 and N7, are decisive for the conformation of the Mn2+ complexes, and this will in turn determine their thermodynamic, kinetic and relaxation properties. We describe the synthesis of four ligands with acetate substituents in positions N3, N7 or both. We evidence that the bispidine conformation is dependent on N3 substitution, with direct impact on the thermodynamic stability, kinetic inertness, hydration state and relaxivity of the Mn2+ complexes. These results unambiguously show that (i) solely a chair-chair conformation allows for favorable inertness and relaxivity, and (ii) in this family such chair-chair conformation is accessible only for ligands without N3-appended carboxylates.

Marine Biomaterials: Hyaluronan.

The marine-derived hyaluronic acid and other natural biopolymers offer exciting possibilities in the field of biomaterials, providing sustainable and biocompatible alternatives to synthetic materials. Their unique properties and abundance in marine sources make them valuable resources for various biomedical and industrial applications. Due to high biocompatible features and participation in biological processes related to tissue healing, hyaluronic acid has become widely used in tissue engineering applications, especially in the wound healing process. The present review enlightens marine hyaluronan biomaterial providing its sources, extraction process, structures, chemical modifications, biological properties, and biocidal applications, especially for wound healing/dressing purposes. Meanwhile, we point out the future development of wound healing/dressing based on hyaluronan and its composites and potential challenges.

Biopolymer-Based Sustainable Food Packaging Materials: Challenges, Solutions, and Applications.

Biopolymer-based packaging materials have become of greater interest to the world due to their biodegradability, renewability, and biocompatibility. In recent years, numerous biopolymers-such as starch, chitosan, carrageenan, polylactic acid, etc.-have been investigated for their potential application in food packaging. Reinforcement agents such as nanofillers and active agents improve the properties of the biopolymers, making them suitable for active and intelligent packaging. Some of the packaging materials, e.g., cellulose, starch, polylactic acid, and polybutylene adipate terephthalate, are currently used in the packaging industry. The trend of using biopolymers in the packaging industry has increased immensely; therefore, many legislations have been approved by various organizations. This review article describes various challenges and possible solutions associated with food packaging materials. It covers a wide range of biopolymers used in food packaging and the limitations of using them in their pure form. Finally, a SWOT analysis is presented for biopolymers, and the future trends are discussed. Biopolymers are eco-friendly, biodegradable, nontoxic, renewable, and biocompatible alternatives to synthetic packaging materials. Research shows that biopolymer-based packaging materials are of great essence in combined form, and further studies are needed for them to be used as an alternative packaging material.

Phytic Acid Demonstrates Rapid Antibiofilm Activity and Inhibits Biofilm Formation When Used as a Surface Conditioning Agent.

Root canal infections are associated with biofilms and are treated with chemical irrigants with a high success rate. However, treatment failure does arise, which is attributed primarily to resistance exhibited by biofilms. Currently used irrigants in root canal treatment have disadvantages, and there is therefore a need for more biocompatible alternatives with antibiofilm properties to reduce root canal treatment failure and complications. The aim of this study was to evaluate the in vitro antibiofilm properties of phytic acid (IP6), which is a potential alternative treatment agent. Single- and dual-species biofilms of Enterococcus faecalis and Candida albicans were developed on the well surfaces of 12-well plates and on hydroxyapatite (HA) coupons, and then exposed to IP6. In addition, selected HA coupons were preconditioned with IP6 before biofilm development. IP6 demonstrated bactericidal effects and altered the metabolic activity of biofilm cells. Confocal laser-scanning microscopy showed that IP6 caused significant and rapid reduction in live biofilm cells. At sublethal concentrations, IP6 did not alter the expression of tested virulence genes except for C. albicans hwp1, the expression of which was upregulated but not reflected by a change in hyphal transformation. IP6-preconditioned HA coupons led to extensive inhibition of dual-species biofilm formation. The results of this study highlight for the first time the antibiofilm inhibitory properties of IP6 and the potential for its exploitation in several clinical applications. IMPORTANCE Root canal infections are biofilm associated, and despite mechanical and chemical treatment procedures, infection recurrence occurs, and this is likely due to the high tolerance of associated biofilms to antimicrobials. The currently used treatment agents have several disadvantages, which necessitates the search for new improved agents. In this study, the natural chemical phytic acid was found to exhibit antibiofilm activity against established mono and dual mature biofilms over a short contact time. Most importantly, phytic acid was found to cause significant inhibition of dual-species biofilm formation when used as a surface preconditioning agent. The findings of this study identified a novel use of phytic acid as a potential antibiofilm agent that can be used in several clinical applications.

Titanium Dioxide Nanoparticles in sunscreens and skin photo-damage. Development, synthesis and characterization of a novel biocompatible alternative based on their in vitro and in vivo study

Titanium dioxide nanoparticles are widely used in cosmetics, especially in sunscreens due to their capacity to absorb UV harmful wavelengths. However, their biocompatibility remains controversial. In this work, the effect of titanium dioxide nanoparticles, particularly Degussa P25 (P25TiO2NPs) under solar-simulated radiation was studied in vitro and in vivo. Cell viability and tissue integrity were affected after exposure to P25TiO2NPs and light for 6 h, showing signs of significant oxidative stress markers and reduced tissue integrity observed by TEM. In order to avoid these undesired effects, a novel biocompatible alternative was presented based on titanium dioxide nanoparticle functionalization with vitamin B2 through a rapid sol-gel method. None of the phototoxicity effects were observed with these functionalized nanoparticles.

Silk fibroin molecularly imprinted nanoparticles as biocompatible molecular nanotraps: Molecular recognition ties the knot with biomaterials. The bioMIP’s labeling and degradation

Molecularly imprinted nanoparticles (nanoMIPs) are biomimetic polymeric nanomaterials, typically prepared from acrylamide and derivatives, that are formed by a template-assisted synthesis. NanoMIPs display high affinity, selectivity, and specificity for the targeted molecule, on the par of natural receptors and antibodies. Recently, we introduced a paradigmatic change by forming nanoMIPs starting from biomaterials, under the name of bioMIPs, as a strategy to promptly translate them into the clinical settings. Silk fibroin, that is a biocompatible and non-immunogenic natural material, was used as a building block for the synthesis of bioMIPs tailored to recognize the protein human serum albumin. BioMIPs confirmed high selectivity and specificity for the targeted protein, together with cytocompatibility. The present work expands the actual knowledge on bioMIPs, studying a route to post-synthetically entail fluorescent tags, with the aim to localize these molecular nanotraps in cells and tissues. Moreover, the enzymatic degradation of bioMIPs was investigated, to support the role of bioMIPs as greener and biocompatible alternatives to non-natural biomimetics.Graphical abstract

Naturally Isolated Sesquiterpene Lactone and Hydroxyanthraquinone Induce Apoptosis in Oral Squamous Cell Carcinoma Cell Line.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of Lycium shawii. The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC50 value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC50 = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents.

Characterisation of cytotoxicity and immunomodulatory effects of glycolipid biosurfactants on human keratinocytes

Skin irritation and allergic reactions associated with the use of skincare products formulated with synthetically derived surfactants such as sodium lauryl ether sulphate (SLES) have encouraged the search for naturally derived and biocompatible alternatives. Glycolipid biosurfactants such as sophorolipids (SL) and rhamnolipids (RL) offer a potential alternative to SLES. However, most studies on the bioactive properties of microbial glycolipids were determined using their mixed congeners, resulting in significant inter-study variations. This study aims to compare the effects of highly purified SL (acidic and lactonic) and RL (mono-RL and di-RL) congeners and SLES on a spontaneously transformed human keratinocyte cell line (HaCaT cells) to assess glycolipids’ safety for potential skincare applications. Preparations of acidic SL congeners were 100% pure, lactonic SL were 100% pure, mono-RL were 96% pure, and di-RL were 97% pure. Cell viability using XTT assays, cell morphological analyses, and immunoassays revealed that microbial glycolipids have differing effects on HaCaT cells dependent on chemical structure. Compared with SLES, acidic SL and mono-RL have negligible effects on cell viability, cell morphology, and production of pro-inflammatory cytokines. Furthermore, at non-inhibitory concentrations, di-RL significantly attenuated IL-8 production and CXCL8 expression while increasing IL-1RA production and IL1RN expression in lipopolysaccharide-stimulated HaCaT cells. Although further studies would be required, these results demonstrate that as potential innocuous and bioactive compounds, microbial glycolipids could provide a substitute to synthetic surfactants in skincare formulations and perform immunopharmacological roles in topical skin infections such as psoriasis.Key points• Purified glycolipid congeners have differing effects on human keratinocytes.• Compared with SLES, acidic sophorolipids and mono-rhamnolipids have innocuous effects on keratinocytes.• Di-rhamnolipids and mono-rhamnolipids modulate cytokine production in lipopolysaccharide stimulated human keratinocytes.

Emerging strategies for environmental decontamination of the nosocomial fungal pathogen Candida auris.

Candida auris is a recently emerged multidrug-resistant fungal pathogen that causes life-threatening infections to the human population worldwide. Recent rampant outbreaks of C. auris in coronavirus disease 2019 (COVID-19) patients, together with outbreaks in over 45 countries, highlight its threat to patients and healthcare economies. Unlike other pathogenic Candida species, C. auris is capable of surviving in abiotic surfaces of healthcare facilities for prolonged periods, leading to increased risk of transmission within nosocomial settings. C. auris is resistant to multiple classes of antifungal agents, forms dry biofilms and transmits independently to regional epicentres, making its eradication from nosocomial environment arduous. The lack of strategies for environmental decontamination of C. auris from nosocomial settings is evident from the generic guidance and recommendations provided by leading global healthcare bodies. Therefore, this minireview discusses the current guidelines for environmental decontamination of C. auris and compounds and strategies currently under investigation for potential future use. While established guidelines recommend the use of products mainly consisting of sodium hypochlorite and hydrogen peroxide, initial works have been reported on the promising anti-C. auris properties of various other compounds and some biocompatible alternatives. Further validation of these approaches, coupled up with environmentally friendly decontamination protocols, are warranted to achieve superior elimination of C. auris from healthcare settings.

Structural Evaluation by the Finite‐Element Method of Hollow Microneedle Geometries for Drug Delivery

Herein, the structural comparison, using the finite‐element method (FEM), of different designs of individual hollow microneedles (MNs) is exposed, that is, conical, pyramidal, traditional, and sting type, for use as a transdermal drug delivery system (TDDS). These configurations attract interest in fields such as pharmaceutics and medicine due to their efficiency, easy administration of drugs, and significant reduction in pain compared to the traditional use of hypodermic needles. For the structural analysis and comparison of the proposed designs, ANSYS FEM‐based software is used to simulate the insertion of an MN in the skin. The study and comparison are carried out under simulations of structural resistance, buckling analysis, and behavior in the MN–skin contact. The application forces are set according to the fracture resistance of the outside layer of the skin. A force of 0.16N for a conical MN is finally obtained as a critical application load to avoid a structural failure in the insertion of the MN in the human skin. Moreover, the use of poly(lactic‐co‐glycolic) acid (PLGA) is also assessed as a second biocompatible alternative due to both its easy handling for manufacture process and the resistance it presents in indentation simulations in which the applied force reaches 0.19N.

Mechanistic Insight on BioIL-Induced Structural Alterations in DMPC Lipid Bilayer.

The emerging application risks of traditional ionic liquids (ILs) toward the ecosystem have changed the perception regarding their greenness. This resulted in the exploration of their more biocompatible alternatives known as biocompatible ILs (BioILs). Here, we have investigated the impact of two such biocompatible cholinium amino acid-based ILs on the structural behavior of model homogeneous DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) lipid bilayer using all-atom molecular dynamics simulation technique. Two classic cholinium-amino acid-based ILs, cholinium glycinate ([Ch][Gly]) and cholinium phenylalaninate ([Ch][Phe]), which differ only by the side chain lengths and hydrophobicity of the anions, have been utilized in the present work. Simultaneous analysis of the bilayer structural properties reveals that the existence of [Ch][Gly] BioIL above a particular concentration induces phase transition from fluid phase to gel phase in the DMPC lipid bilayer. Such a freezing of lipid bilayer upon the exposure to concentrated aqueous solution of [Ch][Gly] BioIL indicates the harmfulness of this BioIL toward the cell membranes majorly containing DMPC lipids, as the cell freezing can negatively affect its stability and functionality. Despite having a more hydrophobic amino acid side chain of [Phe]- anion in [Ch][Phe], in the case of bilayer-[Ch][Phe] systems we observe the minimal impact of [Ch][Phe] BioIL on the DMPC bilayer properties up to 10 mol % concentration. In the presence of these BioIL, we observe the thickening of the bilayer and accumulation of the cations and anions of the BioILs at the interface of DMPC lipid heads and tails. The transfer free-energy profile of a [Phe]- anion from aqueous phase to membrane center also indicates the anion partitioning at lipid head-tail interface and its inability to penetrate in the lipid membrane tail region. In contrast, the free-energy profile for a [Gly]- anion offers a very high energy barrier to the insertion of [Gly]- into the membrane interior, leading to accumulation of [Gly]- anions at the lipid head-water region.