Gelatin Shell Research Articles

Preparation and evaluation of soft gelatin capsules loaded with astaxanthin, niacin and garlic oil for removal of plague in atherosclerosis

Atherosclerosis, a chronic inflammatory disease, is the leading cause of cardiovascular diseases. In atherosclerosis, the arterial walls are characterized by plaque deposits on the inside of arteries. This study focuses on preparing a fill formulation to remove plaque in atherosclerosis, then analyse the pharmaceutical ingredients used and later produce soft gelatin capsules. Soft gelatin capsules are hermetically sealed, one-piece capsule which has a suspension or semi-solid as fill. Oxidative stress and inflammation are factors responsible for the development of atherosclerosis. Hence, the active pharmaceutical ingredients (APIs) chosen for fill formulation need to possess effective anti-oxidant and anti-inflammatory properties. A novel combination of APIs: Astaxanthin, Niacin and Garlic oil were chosen for the removal of plaque in atherosclerosis. Each of these APIs is known to possess a specific function in the control of plaque development. The fill formulation prepared was analysed for its recovery using various analytical techniques like UV spectrophotometry, high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). This fill formulation was encapsulated within the gelatin shell prepared to produce soft gelatin capsules. The encapsulated soft gelatin capsules were evaluated based on various parameters which include average net weight, disintegration test, loss on drying and dissolution.

Multifunctional hyaluronic acid/gelatin methacryloyl core-shell microneedle for comprehensively treating oral mucosal ulcers

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.

Design of Vaterite Nanoparticles for Controlled Delivery of Active Immunotherapeutic Proteins

AbstractDespite clinical advances in immunotherapy, still many therapeutics cause dose‐limiting (auto)immune‐mediated toxicities. Nanoparticle‐based drug delivery systems (DDS) can improve cancer immunotherapy through site‐specific delivery and controlled release of immunotherapeutics in the tumor microenvironment (TME). However, DDS face several challenges, including unspecific release. To address this, vaterite nanoparticles (VNPs) that selectively release immunotherapeutic proteins at low pH conditions find in the TME, are established previously. In the current study, these VNPs are further modified for active targeting without affecting the loaded protein activity, exemplified with Tumor Necrosis Factor α (TNF). Specifically, VNPs are coated with gelatin, a matrix‐metalloprotease sensitive polymer which provides functional groups for further conjugation. Subsequently, streptavidin is covalently linked to the gelatin shell by amine‐epoxy chemistry, enabling coupling of any biotinylated ligand. Exemplified by biotinylated cetuximab and rituximab, targeted VNPs selectively bind to cells expressing epidermal growth factor receptor (EGFR) or CD20, respectively. Importantly, TNF remains functionally active after the modification steps, as VNP treatment increased ICAM‐1 expression on FaDu cells and activated NFκB signaling in a Jurkat.NFκB‐luciferase cell line model. In conclusion, a targetable vaterite‐based DDS is produced that allows for easy surface modification with any biotinylated ligand that may find broad applications in tumor‐selective immunotherapy.

A Novel Activatable Nanoradiosensitizer for Second Near-Infrared Fluorescence Imaging-Guided Safe-Dose Synergetic Chemo-Radiotherapy of Rheumatoid Arthritis.

The precise theranostics of rheumatoid arthritis (RA) remains a formidable challenge in clinical practice. Exploring novel applications of contemporary therapeutic approaches like chemo-radiotherapy is promising as a highly effective strategy for RA. Herein, a novel activatable nanoradiosensitizer-40 (denoted as IRnR-40) is developed, based on encapsulating the clinically approved drugs cisplatin (DDP) and indocyanine green (ICG) within a gelatin shell to achieve second near-infrared fluorescence (NIR-II FL) imaging-guided safe-dose synergetic chemo-radiotherapy. The high concentration of matrix metalloproteinase-9 (MMP-9) in the RA microenvironment plays a pivotal role in triggering the responsive degradation of IRnR-40, leading to the rapid release of functional molecules DDP and ICG. The released ICG serves the dual purpose of illuminating the inflamed joints to facilitate accurate target volume delineation for guiding radiotherapy, as well as acting as a real-time reporter for quantifying the release of DDP to monitor efficacy. Meanwhile, the released DDP achieves highly effective synergistic chemotherapy and radiosensitization for RA via the dual reactive oxygen species (ROS)-mediated mitochondrial apoptotic pathway. To sum up, this activatable nanoradiosensitizer IRnR-40 is believed to be the first attempt to achieve efficient NIR-II FL imaging-guided safe-dose chemo-radiotherapy for RA, which provides a new paradigm for precise theranostics of refractory benign diseases.

Microenvironment-responsive bilayer hydrogel microspheres with gelatin-shell for osteoarthritis treatment

Osteoarthritis is a long-term degenerative condition of the joints that is characterized by the breakdown of cartilage and inflammation of the synovial membrane. The presence of an inflammatory microenvironment and the degradation of the extracellular matrix produced by chondrocytes leads to the aggravation of cartilage injury, hindering the treatment of osteoarthritis. A promising approach to address this issue is to apply a combined strategy that is sensitive to the specific conditions in osteoarthritic joints and possesses properties that can reduce inflammation and promote cartilage healing. Here, inspired by the structure of chocolate-covered peanuts, we developed an injectable, environment-responsive bilayer hydrogel microsphere using microfluidics technology. The microsphere applied chondroitin sulfate methacryloyl (ChsMA) as its core and was coated with a methacryloyl gelatin (GelMA) shell that was loaded with celecoxib (CLX) liposomes (ChsMA+CLX@Lipo@GelMA). CLX was released from the liposomes when the GelMA shell rapidly degraded in response to the osteoarthritic microenvironment and suppressed the generation of inflammatory agents, demonstrating a beneficial impact of the outer shell in reducing inflammation. While the inner methacryloyl microsphere core degraded, chondroitin sulfate was released to promote chondrocyte anabolism and facilitate cartilage repair. Thus, the synthesized bilayer hydrogel microspheres hold great potential for treating osteoarthritis.

Intracellular delivery, imaging and drug-sensing using a plasmonic-enhanced hybrid nanostystem

Metastasis stands as the leading cause of mortality among colorectal cancer (CRC) patients. Galunisertib (LY2157299, LY) is a small molecule demonstrating promising anti-cancer effects by targeting the Transforming Growth Factor-beta (TGF-β) pathway. This route plays a pivotal role in initiating the epithelial-to-mesenchymal transition (EMT), a critical process for metastatic spread. Unfortunately, LY chronic treatment causes undesired effects. To mitigate these side effects, nanoscale drug delivery systems have emerged as a transformative approach in cancer treatment, enhancing drug effectiveness while minimizing toxicity. In this study, we introduce a hybrid nanosystem (DNP-AuNPs-LY@Gel) comprising porous diatomite nanoparticles decorated with plasmonic gold nanoparticles (AuNPs), encapsulating LY within a gelatin shell. This multifunctional nanosystem demonstrates efficient LY delivery, EMT reversal in CRC 2D and 3D cultures, and anti-cancer effects in vivo. Moreover, the nanosystem allowed the quantification with sub-femtogram resolution of the drug intracellularly released using surface-enhanced Raman spectroscopy (SERS). The release of LY is triggered by CRC cell acidic microenviroment. Real-time monitoring of drug release at the single-cell level is achieved by analyzing SERS signals of LY within CRC cells. The heightened efficacy of LY delivery through the DNP-AuNPs-LY@Gel complex offers a promising alternative strategy for reducing drug dosages and subsequent undesired effects.

The Influence of the Specifics of the Formation of the Polymer Shell of a Microcapsule with a Nitrogen-Containing Compound Core on the Durability of the Tool During Blade Cutting

Microcapsules with gelatin shells are obtained by coacervation. In the process of microcapsulation,the shells of microcapsules are treated with ozone and ozonated water is introduced into their core. Magneticsensitivity was imparted to microcapsules by introducing magnetite in their shell. The influence of the compositionand concentration of microcapsules in an aqueous emulsion on the durability of the tool during bladecutting is studied. It is shown that the lubricating and cooling technological means obtained by introducingozonated water into the core of a gelatin microcapsule is more effective for increasing the tool’s durabilityduring blade cutting.

Shell Formulation in Soft Gelatin Capsules: Design and Characterization.

Soft gelatin capsules (SGCs)are the most widely used pharmaceutical form after tablets. The active components, active pharmaceutical ingredients (APIs), or nutrients are dissolved, dispersed, or suspended in a liquid or semisolid fill, which is covered with a gelatin shell. Several factors can modify the properties of the gelatin shell and subsequently affect their operative handling during manufacturing process and the stability of the soft gelatin capsules. Three elements appear to be crucial: the shell formulation (type and content of the different components such as gelatins-source, extraction method-plasticizers, or additives); the manufacture and storage conditions (temperature, humidity, light) as well as the interactions between fill-shell formulas. Mechanical and thermal analysis arise as straightforward but highly useful tools to monitor the properties of the gelatin shell. This review provides an updated overview on the shell formulation and design. Additionally, it presents the uses of mechanical and thermal techniques to characterize and evaluate the impact of different parameters on the gelatin behavior over the production and stability of these pharmaceutical forms. This will help to detect changes that are yet not visible by visual inspection ensuring a suitable finished product over its shelf-life.

Duocapsule and alternative shell material to gelatin: Advancement in capsule formulation

Owing to broad advantages like self-medication, unit dosage form, and patient compliance, cost effective, limited interaction with the excipients and possibility of mask the unpleasant taste, capsules are the most extensively recognized conventional solid dosage form after Tablet. In the world of Novel drug delivery system to overcome the disadvantages of conventional delivery system modifications are made in the capsule to develop a product of higher selectivity for medical treatment like the capsules that facilitates the controlled drug delivery, sustained and targeted release profiles with its own benefits as conventional dosage form. The advancement in capsules has led to the formation of different types of capsule formulations such as tablets in capsules, pellets in capsule and the capsule in another capsule, liquid in capsule products and pellets in capsule formulations. This article aims to highlights the advancement in the capsule system, particularly Duocapsules and capsules with capsule shell prepared with alternative shell material to gelatin. The Duo capsule is also called as capsule in capsule formulation as it contains two capsules one with the bigger size containing the smaller sized capsule inside it with different or same formulations in various forms such as liquids, solids, powders, tablets, pellets etc. The article mainly focuses on the different applications, advantages, formulation consideration, and applicable drugs of duo capsules. Considering the challenges invovled in manufacturing the gelatin shell and unstability of in different climatic conditions, the present article also emphasizes on the formulation development in capsule system with alternative polymers to the gelatin like HPMC, starch and PVA copolymer capsule shells.

Dual-Functional Nanofibrous Patches for Accelerating Wound Healing.

Bacterial infections and inflammation are two main factors for delayed wound healing. Coaxial electrospinning nanofibrous patches, by co-loading and sequential co-delivering of anti-bacterial and anti-inflammation agents, are promising wound dressing for accelerating wound healing. Herein, curcumin (Cur) was loaded into the polycaprolactone (PCL) core, and broad-spectrum antibacterial tetracycline hydrochloride (TH) was loaded into gelatin (GEL) shell to prepare PCL-Cur/GEL-TH core-shell nanofiber membranes. The fibers showed a clear co-axial structure and good water absorption capacity, hydrophilicity and mechanical properties. In vitro drug release results showed sequential release of Cur and TH, in which the coaxial mat showed good antioxidant activity by DPPH test and excellent antibacterial activity was demonstrated by a disk diffusion method. The coaxial mats showed superior biocompatibility toward human immortalized keratinocytes. This study indicates a coaxial nanofiber membrane combining anti-bacterial and anti-inflammation agents has great potential as a wound dressing for promoting wound repair.

Coaxial electrospun angiogenic nanofiber wound dressing containing advanced platelet rich-fibrin

Advanced platelet-rich fibrin (A-PRF) provides long-term release of growth factors that potentially accelerate wound healing. In this study, core-shell nanofibrous structure of polyvinyl alcohol (PVA) core and gelatin (Gel) shell containing A-PRF is fabricated through coaxial electrospinning method. PVA/(Gel/A-PRF) core-shell nanofibers had the highest porosity, specific surface area and hydrophilicity among all the studied nanofibers. PVA/(Gel/A-PRF) core-shell nanofibers with a tensile stress of 7.43 ± 0.38 MPa and an elastic modulus of 102.05 ± 9.36 MPa had higher mechanical properties than PVA/Gel/A-PRF and PVA/Gel blend nanofibers. PVA/(Gel/A-PRF) nanofibers had a 47.41 ± 1.97 % degradability over 7 days of immersion in PBS. The release of VEGF and PDGF-AB growth factors from PVA/(Gel/A-PRF) core-shell nanofibers and PVA/Gel/A-PRF blend nanofibers were evaluated. It was shown that L929 cell proliferation and adhesion on PVA/(Gel/A-PRF) core-shell nanofibers were significantly higher than other samples. Also, chicken chorioallantoic membrane (CAM) assay revealed that the highest angiogenic potential among the studied samples related to PVA/(Gel/A-PRF) sample. In vivo studies on a rat model showed wound closure for PVA/(Gel/A-PRF) group was 97.83 ± 2.03 % after 11 days. Histopathological and immunohistochemical examinations approved the acceleration of wound healing by PVA/(Gel/A-PRF) core-shell nanofiber dressing. The results strongly recommend the use of PVA/(Gel/A-PRF) core-shell nanofiber dressing for the repair of full-thickness wounds.

Prussian Blue Nanozymes with Enhanced Catalytic Activity: Size Tuning and Application in ELISA-like Immunoassay.

Prussian blue nanozymes possessing peroxidase-like activity gather significant attention as alternatives to natural enzymes in therapy, biosensing, and environmental remediation. Recently, Prussian blue nanoparticles with enhanced catalytic activity prepared by reduction of FeCl3/K3[Fe(CN)6] mixture have been reported. These nanoparticles were denoted as ‘artificial peroxidase’ nanozymes. Our study provides insights into the process of their synthesis. We studied how the size of nanozymes and synthesis yield can be controlled via adjustment of the synthesis conditions. Based on these results, we developed a reproducible and scalable method for the preparation of ‘artificial peroxidase’ with tunable sizes and enhanced catalytic activity. Nanozymes modified with gelatin shell and functionalized with affine molecules were applied as labels in colorimetric immunoassays of prostate-specific antigen and tetanus antibodies, enabling detection of these analytes in the range of clinically relevant concentrations. Protein coating provides excellent colloidal stability of nanozymes in physiological conditions and stability upon long-term storage.

Pharmacological and biopharmaceutical studies of paracetamol and N-acetyl-D-glucosamine combination as an analgetic drug

The aim. Experimental selection of paracetamol and N-acetyl-D-glucosamine (NAG) ratio and combined dose and bioavailability study of the pharmaceutical composition and active pharmaceutical ingredient (API) in the model of cell biomembranes.
 Materials and methods. The following substances were used: paracetamol, Actimask Acetaminophen (gelatin-coated paracetamol), and NAG. For pharmacological studies were used laboratory rats, which received test objects intragastrically. The study was performed on the model of inflammatory hyperalgesia according to the Randall-Selitto method. The values of pain threshold before and after pathology induction were established. For biopharmaceutical studies, dry L-α-dimyristoylphosphatidylcholine purchased from Avanti Polar Lipids (purity 99.9 %) was used, hydrated with an appropriate amount of double-distilled water to obtain 70 % wt./wt. water dispersion. Differential scanning calorimetry (DSC) studies were performed employing DSC 1 microcalorimeter (Mettler Toledo). Pharmaceuticals investigated were placed on the bottom of a crucible, then a proper amount of the lipid membrane was added and this moment was taken as the time reference point (t=0). Then a crucible was sealed with a lid and a sample was undergone consecutive temperature scans, heating from 0 to 35 ºC at a scanning rate of 2 ºC/min. The procedure was repeated until no more changes in DSC profiles were observed, i.e. system equilibrium was reached.
 Results. It has been experimentally proven that the combination of paracetamol and NAG in the ratio of 4:1 showed better analgesic efficacy. The dose of active ingredients was determined to be 50 mg/kg by the sum of API. The active interaction of paracetamol with the bilayer of biomembranes was established and it was determined that Actimask has a worse rate of penetration into the membrane due to the coating of paracetamol with a gelatin shell. NAG didn't significantly affect the rate of penetration of Actimask through the bilayer of membranes, but the auxiliary components of the tablet mixture significantly improved the rate and completeness of penetration of paracetamol through the bilayer of biomembranes.
 Conclusions. The study found the most effective ratio between paracetamol and NAG in the composition, which is 4:1. The next step was to determine the dose of API, which is 50 mg/kg of the sum of active substances. It has been determined that paracetamol has good permeability through the bilayer of biomembranes, and the tablet mass significantly improves the permeability of paracetamol

Experimental substantiation of the composition of gelatin mass for obtaining capsules with essential oils

Introduction. Soft gelatin capsules are a promising dosage form comprising essential oils as active agents. Joint research of the staff of the Perm State Pharmaceutical Academy, the Research Institute of Nutrition of the Ministry of Energy and Industry of the Republic of Tajikistan have proposed the composition of gelatin mass for encapsulation by the rotary matrix method. The mechanical and physical-technological parameters required to preserve the strength and elasticity of the capsule shell during the production process and storage are determined.Aim. Study of the rheological properties of gelatin masses based on gelatin of different grades, as well as the migration of essential oils through capsule shells.Materials and methods. Pharmaceutical active substances "Lipovitol" and "Limoneol" obtained in the Republic of Tajikistan were used as active substances introduced into the composition of soft gelatin capsules. Sunflower oil was used as the solvent. Gelatin samples were used to obtain gelatin masses: 1 – Foodchem (China), 2 – Brodnickie Zaklady Zelatyny Sp. zo.o. (Poland), 3 - Italgelatine s.p.a. (Italy), 4 – Ewald-Gelatine GmbH (Germany), 5 – Weishardt International (France); glycerol; sunflower oil. Gelatin mass for manufacturing soft capsules was prepared in a closed reactor. Capsules were prepared on an automatic encapsulation line RJWJ – 115 Soft Gelatin Encapsulator Machine (China). The structural and mechanical properties of soft gelatin masses were determined on a rotary viscometer RV type "Reotest 2" (Germany). The dynamics of the process of migration of essential oils and its components were studied by changing their amount in a capsule by chromato-mass spectrometry method on a chromatograph Varian CP 3800 with a quadrupole mass spectrometer 4000 MS as a detector (USA).Results and discussion. When studying the rheological properties of model compositions, it was found that for all samples of gelatin masses there is a decrease in values of effective viscosity when the shear rate increases, which characterizes the tested samples as a structured dispersion system. Additional studies have shown that the gelatin masses have thixotropic properties. Samples of gelatin masses 3–5 had narrower hysteresis loops, while sample 5 the narrowest, restoration of the structure took place quite quickly. Capsules obtained from gelatin mass 3 and 4 samples had a strong seam and were well cut out of the tape. From the mass of sample 5, high strength ribbons were obtained, a high temperature was required to seal the capsules, in some capsules the seam was not glued on one side, as a result, the capsules were rigid and brittle. As a result of the study, the rheological optimum of the gelatin mass suitable for preparing capsules by a rotary matrix method was determined, which has boundaries in the ranges of shear rates of 0.556–243 s-1 and viscosity ranges of 11.46-5028.76 Pa ⋅ s and shear stress of 2788–2808 Pa developing at these rates. When studying the migration of active substances through the capsule shell, it was found that over three years of storage of capsules in a closed polymer can, the content of essential oil in Lipovitol capsules decreased by 4.88 %, in Limoneol capsules by 5 %, which indicates partial migration of oil through the gelatin shell. The content remained within the permissible deviations (±10 %). The content of essential essential oil components also remained within acceptable deviations throughout the shelf life.Conclusion. The optimal composition of the shell for producing soft capsules by a rotary matrix method is justified. It was found that the rheological optimum of gelatin mass is characterized by viscosity ranges of 11.46-5028.76 Pa ⋅ s and shear stress of 2788–2808 Pa. According to the results of the study of the migration of essential oils through the shell, has been established the shelf life of soft gelatin capsules in glass jars made of dark glass and a temperature of 15 to 25 °C – 3 years.

Development of Platform Technology for Gastro-resistant Soft Gel Capsules by Using Cross-linking Technique

Introduction: Conventional enteric coating is very challenging in soft gel capsules because of their shell nature (smooth surfaces and elasticity). Soft gelatin capsules are highly sensitive to temperature, humidity and they can lose their tensile strength during the conventional coating process. Materials and Methods: Enteric soft gel capsules were prepared by the addition of enteric polymer in the gelatin shell composition by inducing the cross-linking of gelatin through chemical treatment. Results: This dual approach makes the soft gelatin capsules resist the drug release in the stomach and reliably release their contents in the intestine within a predetermined time without affecting the physical properties of soft gel capsules. Conclusions: Enteric effects of soft gel capsules are brought by a specialized synergetic technique, which is unique for the molecules, requiring intestinal drug release.

Sustained-release capsules coated via thermoforming techniques

Capsule coatings have a wide range of applications as they afford protection to active pharmaceutical ingredients. However, few studies have focused on capsule coating owing to the sensitivity of hard gelatin shells to solvents and high temperature. In the present study, we aimed to coat capsules using two thermoforming coating techniques: vacuum forming coating (VFC) and centrifugal forming coating (CFC). Rheological and mechanical properties were investigated to comprehensively elucidate the processes and mechanisms underlying the two coating techniques. The corresponding coating integrity and drug release behavior were characterized and compared. Herein, we observed that a lower temperature was more suitable for the VFC process than the CFC process. The drug release rate decreased with the film thickness increased. Both optimal VFC and CFC capsules revealed a 24 h sustained-release property following Fick's diffusion law. The coating thickness distribution was more homogeneous for the VFC capsule than the CFC capsule. With the advantage solvent-free of functional capsule coatings, thermoforming coating techniques are convenient and efficient solutions for small-scale personalized coating of oral solid preparations.

Colorimetric and label free detection of gelatinase positive bacteria and gelatinase activity based on aggregation and dissolution of gold nanoparticles

A simple and sensitive method was developed for the detection of bacteria gelatinase activity based on their enzymatic hydrolysis effect on the surface plasmon resonance (SPR) of gelatin functionalized gold nanoparticles (Au@gelatin NPs) in bacteria supernatant. Characterization of synthesized NPs showed a very thin gelatin layer on the surface of about 20 nm AuNPs which modified the intrinsic SPR property of AuNPs. The extracted supernatants of applied bacteria were incubated with Au@gelatin NPs. Gelatinase activity of bacteria resulted in gradual gelatin shell removal and subsequent dissolution of bare AuNPs. The presence of inducer agents such as NaCl as the common ingredient in the bacterial medium led to the aggregation process of AuNPs and further bacterial activity resulted in AuNPs dissolution. AuNPs colloid solution color was changed from red to purple after addition of bacteria supernatants with gelatinase activity to the reaction. Also, the spectroscopic studies showed that the gelatinase activity of bacteria resulted in the gradual decrease of absorbance at 529 nm and subsequently led to extinction of SPR characteristics. So, the observed absorbance decrease in UV–Vis spectra at 529 nm was indicated as the gelatinase activity of applied bacteria. Different strains of gelatinase positive Bacillus strains were used as the real sample and their gelatinase activity was determined in the present study. Also, sensitivity analysis of the applied method was determined through this method and the obtained results showed Bacillus subtilis gelatinase activity in the linear range of 0–120 U/mL and detection limit of 0.5 U/mL. This method introduced label free, facile and sensitive assay of the bacterial gelatinase activity without any complicated instrument, affording convenience and simplicity.

Design of Gelatin-Capped Plasmonic-Diatomite Nanoparticles with Enhanced Galunisertib Loading Capacity for Drug Delivery Applications.

Inorganic diatomite nanoparticles (DNPs) have gained increasing interest as drug delivery systems due to their porous structure, long half-life, thermal and chemical stability. Gold nanoparticles (AuNPs) provide DNPs with intriguing optical features that can be engineered and optimized for sensing and drug delivery applications. In this work, we combine DNPs with gelatin stabilized AuNPs for the development of an optical platform for Galunisertib delivery. To improve the DNP loading capacity, the hybrid platform is capped with gelatin shells of increasing thicknesses. Here, for the first time, full optical modeling of the hybrid system is proposed to monitor both the gelatin generation, degradation, and consequent Galunisertib release by simple spectroscopic measurements. Indeed, the shell thickness is optically estimated as a function of the polymer concentration by exploiting the localized surface plasmon resonance shifts of AuNPs. We simultaneously prove the enhancement of the drug loading capacity of DNPs and that the theoretical modeling represents an efficient predictive tool to design polymer-coated nanocarriers.

SERS Quantification of Galunisertib Delivery in Colorectal Cancer Cells by Plasmonic-Assisted Diatomite Nanoparticles.

The small molecule Galunisertib (LY2157299, LY) shows multiple anticancer activities blocking the transforming growth factor-β1 receptor, responsible for the epithelial-to-mesenchymal transition (EMT) by which colorectal cancer (CRC) cells acquire migratory and metastatic capacities. However, frequent dosing of LY can produce highly toxic metabolites. Alternative strategies to reduce drug side effects can rely on nanoscale drug delivery systems that have led to a medical revolution in the treatment of cancer, improving drug efficacy and lowering drug toxicity. Here, a hybrid nanosystem (DNP-AuNPs-LY@Gel) made of a porous diatomite nanoparticle decorated with plasmonic gold nanoparticles, in which LY is retained by a gelatin shell, is proposed. The multifunctional capability of the nanosystem is demonstrated by investigating the efficient LY delivery, the enhanced EMT reversion in CRCs and the intracellular quantification of drug release with a sub-femtogram resolution by surface-enhanced Raman spectroscopy (SERS). The LY release trigger is the pH sensitivity of the gelatin shell to the CRC acidic microenvironment. The drug release is real-time monitored at single-cell level by analyzing the SERS signals of LY in CRC cells. The higher efficiency of LY delivered by the DNP-AuNPs-LY@Gel complex paves the way to an alternative strategy for lowering drug dosing and consequent side effects.

Features of a simvastatin-loaded multi-layered co-electrospun barrier membrane for guided bone regeneration.

A novel tri-layer membrane consisting of polycaprolactone (PCL) fibrous sheets and structured nanofibers with a gelatin (Gt) shell and a simvastatin-containing PCL core (PCL-Gt/PCL-simvastatin membrane) was prepared. The soft external layer comprised of Gt/PCL-simvastatin, the external layer of PCL and the middle layer of both microfilaments, interwoven together. The membrane was designed to promote osteoinduction and act as a barrier against cells but not against water and molecules in order to promote guided bone regeneration. The structure of the membrane was characterized by scanning electronic microscopy. The in vitro release rates of simvastatin over 32 days were determined by high-performance liquid chromatography. For in vitro biological assays, bone marrow mesenchymal stem cells and human fibroblasts were cultured on the different surfaces of the membrane. Cell adhesion, proliferation, distribution, and differentiation were examined. For in vivo testing, cranial defects were created in rabbits to assess the amount of new bone formed for each membrane. The results revealed that membranes with multi-layered structures showed good cell viability and effective osteoinductive and barrier properties. These results suggest that the novel multi-layered PCL-Gt/PCL-simvastatin membranes have great potential for bone tissue engineering.