Surface entrenched ß-sitosterol niosomes for enhanced cardioprotective activity against isoproterenol induced cardiotoxicity in rats.

Cardiotoxicity (CT) is a severe condition that negatively impacts heart function. ß-sitosterol (BS) is a group of phytosterols and known for various pharmacological benefits, such as managing diabetes, cardiac protection, and neuroprotection. This study aims to develop niosomes (NS) containing BS, utilizing cholesterol as the lipid and Tween 80 as the stabilizer. The research focuses on designing and evaluating both conventional BS-NS and hyaluronic acid (HA) modified NS (BS-HA-NS) to enhance the specificity and efficacy of BS within cardiac tissue. The resulting niosomal formulation was spherical, with a size of about 158.51 ± 0.57 nm, an entrapment efficiency of 93.56 ± 1.48 %, and a drug loading of 8.07 ± 1.62 %. To evaluate cytotoxicity on H9c2 heart cells, the MTT assay was used. The cellular uptake of BS-NS and BS-HA-NS was confirmed by confocal microscopy on H9c2 cardiac cells. Administering BS-NS and BS-HA-NS intravenously at a dose of 10 mg/kg showed the ability to significantly decrease the levels of cardiac troponin-I (cTn-I), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and lipid peroxidation (MDA). Tissue histopathology indicated a substantial potential for repairing cardiac tissue after treatment with BS-NS and BS-HA-NS and strong cardioprotection against ISO induced myocardial tissue damages. Thus, enhancing BS's therapeutic effectiveness through niosome surface modification holds promise for mitigating cardiac damage resulting from CT.

c(RGDfK) anchored surface manipulated liposome for tumor-targeted tyrosine kinase inhibitor (TKI) delivery to potentiate liver anticancer activity.

Current anticancer drug research includes tumor-targeted administration as a critical component because it is the best strategy to boost efficacy and decrease toxicity. Low drug concentration in cancer cells, nonspecific distribution, rapid clearance, multiple drug resistance, severe side effects, and other factors contribute to the disappointing results of traditional chemotherapy. As an innovative technique of treatments for hepatocellular carcinoma (HCC) in recent years, nanocarrier-mediated targeted drug delivery systems can overcome the aforesaid limitations via enhanced permeability and retention effect (EPR) and active targeting. Epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Gefi) has dramatic effects on hepatocellular carcinoma. Herein, we developed and assessed an αvß3 integrin receptor targeted c(RGDfK) surface modified liposomes for better targeting selectivity and therapeutic efficacy of Gefi on HCC cells. The conventional and modified Gefi loaded liposomes, i.e., denoted as Gefi-L and Gefi-c(RGDfK)-L, respectively, were prepared through the ethanol injection method and optimized via Box Behnken design (BBD). The FTIR and 1H NMR spectroscopy verified that the c(RGDfK) pentapeptides had formed an amide bond with the liposome surface. In addition, the particle size, Polydispersity index, zeta potential, encapsulation efficiency, and in-vitro Gefi release of the Gefi-L and Gefi-c(RGDfK)-L were measured and analyzed. As indicated by the MTT assay on HepG2 cells, Gefi-c(RGDfK)-L displayed considerably higher cytotoxicity than Gefi-L or Gefi alone. Throughout the incubation period, HepG2 cells took up significantly more Gefi-c(RGDfK)-L than Gefi-L. According to the in vivo biodistribution analysis, Gefi-c(RGDfK)-L accumulated more strongly at the tumor site than Gefi-L and free Gefi. Furthermore, HCC-bearing rats treated with Gefi-c(RGDfK)-L showed a substantial drop in liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and total bilirubin levels) compared to the disease control group. Gefi-c(RGDfK)-L suppresses tumour growth more effectively than Gefi-L and free Gefi, according to an in vivo analysis of their anticancer activities. Thus, c(RGDfK)-surface modified liposomes, i.e., Gefi-c(RGDfK)-L may serve as an efficient carrier for the targeted delivery of anticancer drugs.

Biomimicking dual drug eluting twisted electrospun nanofiber yarns for post-operative wound healing.

The morbidity rate following a surgical procedure increasing rapidly in the cases associated with surgical site infections. Traditional sutures lack the ability to deliver drugs as the incorporation of the drug in their structure would hamper their mechanical properties. To prevent such infections, we developed an extracellular matrix mimicking electrospun nanofibrous yarns of poly-(D,L)-lactic acid and polyvinyl alcohol loaded with vancomycin and ferulic acid, prepared by uniaxial electrospinning technique.In-vitrocharacterization such as scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, tensile strength testing, degradation studies, and antimicrobial studies along within-vivoevaluation done with help of incision wound healing rat model and simultaneous testing of microbial load in the incised tissue. Thein-vitrostudies indicated the nanofiber yarns have size range 200-300 nm with a tensile strength of 7.54 ± 0.58 MPa. The dual drug-loaded yarn showed sustained drug release over a period of 48 h.In-vitrowater uptake and biodegradation data indicated optimum results suitable for suturing applications. Antimicrobial study showed excellent antimicrobial activity against bothS. aureus and E. coli.Results obtained fromin-vivostudy suggested excellent wound healing potential of nanofiber yarns as compared with commercial silk sutures. The histopathological studies confirmed restoring ability of nanofiber yarn to the normal skin structure. Enzyme-linked immunosorbent assay (ELISA) study revealed the downregulation of inflammatory markers i.e. TNF-alpha and IL-6, making nanofibers sutures suitable for surgical wound healing applications. Overall, the present study may conclude that the developed dual drug-loaded nanofiber yarns have excellent potential in surgical wound healing applications.

Novel Synergistic Approach: Tazarotene-Calcipotriol-Loaded-PVA/PVP-Nanofibers Incorporated in Hydrogel Film for Management and Treatment of Psoriasis.

Psoriasis is an autoimmune skin disease that generally affects 1%-3% of the total population globally. Effective treatment of psoriasis is limited because of numerous factors, such as ineffective drug delivery and efficacy following conventional pharmaceutical treatments. Nanofibers are widely being used as nanocarriers for effective treatment because of their multifunctional and distinctive properties, including a greater surface area, higher volume ratio, increased elasticity and improved stiffness and resistance to traction, favorable biodegradability, high permeability, and sufficient oxygen supply, which help maintain the moisture content of the skin and improve the bioavailability of the drugs. Similar to the extracellular matrix, nanofibers have a regeneration capacity, promoting cell growth, adhesion, and proliferation, and also have a more controlled release pattern compared with that of other conventional therapies at the psoriatic site. To ensure improved drug targeting and better antipsoriatic efficacy, this study formulated and evaluated a tazarotene (TZT)-calcipotriol (CPT)-loaded nanofiber and carbopol-based hydrogel film. The nanofiber was prepared using electrospinning with a polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) K-90 polymeric blend that was later incorporated into a carbopol base to form hydrogel films. The prepared nanofibers were biochemically evaluated and in vitro and in vivo characterized. The mean diameters of the optimized formulation, i.e., TZT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-PVA/PVP-NF) and TZT-CPT-loaded polyvinyl alcohol/polyvinylpyrrolidone nanofiber (TZT-CPT-PVA/PVP-NF) were 244.67 ± 58.11 and 252.31 ± 35.50 nm, respectively, as determined by scanning electron microscopy, and their tensile strength ranged from 14.02 ± 0.54 to 22.50 ± 0.03 MPa. X-ray diffraction revealed an increase in the amorphous nature of the nanofibers. The biodegradability studies of prepared nanofiber formulations, irrespective of their composition, showed that these completely biodegraded within 2 weeks of their application. The TZT-CPT-PVA/PVP-NF nanofibers exhibited 95.68% ± 0.03% drug release at the end of 72 h, indicating a controlled release pattern and following Higuchi release kinetics as a best-fit model. MTT assay, antioxidant and lipid profile tests, splenomegaly assessment, and weight fluctuation were all performed in the in vitro as well as in vivo studies. We found that the TZT-CPT-PVA/PVP-NF-based hydrogel film has high potential for antipsoriatic activity in imiquimod-induced Wistar rats in comparison with that of TT-PVA/PVP-NF nanofibers.

Electrospun Biomimetic Nanofibrous Scaffolds: A Promising Prospect for Bone Tissue Engineering and Regenerative Medicine.

Skeletal-related disorders such as arthritis, bone cancer, osteosarcoma, and osteoarthritis are among the most common reasons for mortality in humans at present. Nanostructured scaffolds have been discovered to be more efficient for bone regeneration than macro/micro-sized scaffolds because they sufficiently permit cell adhesion, proliferation, and chemical transformation. Nanofibrous scaffolds mimicking artificial extracellular matrices provide a natural environment for tissue regeneration owing to their large surface area, high porosity, and appreciable drug loading capacity. Here, we review recent progress and possible future prospective electrospun nanofibrous scaffolds for bone tissue engineering. Electrospun nanofibrous scaffolds have demonstrated promising potential in bone tissue regeneration using a variety of nanomaterials. This review focused on the crucial role of electrospun nanofibrous scaffolds in biological applications, including drug/growth factor delivery to bone tissue regeneration. Natural and synthetic polymeric nanofibrous scaffolds are extensively inspected to regenerate bone tissue. We focused mainly on the significant impact of nanofibrous composite scaffolds on cell adhesion and function, and different composites of organic/inorganic nanoparticles with nanofiber scaffolds. This analysis provides an overview of nanofibrous scaffold-based bone regeneration strategies; however, the same concepts can be applied to other organ and tissue regeneration tactics.

Electrospun Biomimetic Multifunctional Nanofibers Loaded with Ferulic Acid for Enhanced Antimicrobial and Wound-Healing Activities in STZ-Induced Diabetic Rats.

Diabetic foot ulceration is the most distressing complication of diabetes having no standard therapy. Nanofibers are an emerging and versatile nanotechnology-based drug-delivery system with unique wound-healing properties. This study aimed to prepare and evaluate silk-sericin based hybrid nanofibrous mats for diabetic foot ulcer. The nanofibrous mats were prepared by electrospinning using silk sericin mixed with different proportions of polycaprolactone (PCL) and cellulose acetate (CA) loaded with ferulic acid (FA). The in vitro characterizations, such as surface morphology, mechanical properties, swelling behavior, biodegradability, scanning electron microscopy, and drug release were carried out. The SEM images indicated that nanofibers formed with varied diameters, ranging from 100 to 250 nm, and their tensile strength was found to range from 7 to 15 MPa. In vitro release demonstrated that the nanofibers sustained FA release over an extended time of period. In vitro cytotoxicity showed that the nanofibers possessed a lower cytotoxicity in HaCaT cells. The in vivo wound-healing studies demonstrated an excellent wound-healing efficiency of the nanofibers in diabetic rats. Furthermore, the histopathological studies showed the nanofibers' ability to restore the skin's normal structure. Therefore, it was concluded that the prepared silk-sericin-based hybrid nanofibers loaded with FA could be a promising drug-delivery platform for the effective treatment of diabetic foot ulcers.

Multifunctional Biomimetic Nanofibrous Scaffold Loaded with Asiaticoside for Rapid Diabetic Wound Healing.

Diabetes mellitus is a chronic disease with a high mortality rate and many complications. A non-healing diabetic foot ulcer (DFU) is one the most serious complications, leading to lower-extremity amputation in 15% of diabetic patients. Nanofibers are emerging as versatile wound dressing due to their unique wound healing properties, such as a high surface area to volume ratio, porosity, and ability to maintain a moist wound environment capable of delivering sustained drug release and oxygen supply to a wound. The present study was aimed to prepare and evaluate a polyvinyl alcohol (PVA)-sodium alginate (SA)-silk fibroin (SF)-based multifunctional nanofibrous scaffold loaded with asiaticoside (AT) in diabetic rats. The SEM findings showed that fibers' diameters ranged from 100-200 nm, and tensile strengths ranged from 12.41-16.80 MPa. The crosslinked nanofibers were sustained AT over an extended period. The MTT and scratch assay on HaCat cells confirmed low cytotoxicity and significant cell migration, respectively. Antimicrobial tests revealed an excellent anti-microbial efficacy against P. aeruginosa and S. aureus bacteria. In-vivo study demonstrated better wound healing efficacy in diabetic rats. In addition, the histopathological studies showed its ability to restore the normal structure of the skin. The present study concluded that developed multifunctional nanofibers have a great potential for diabetic wound healing applications.

ECM Mimicking Biodegradable Nanofibrous Scaffold Enriched with Curcumin/ZnO to Accelerate Diabetic Wound Healing via Multifunctional Bioactivity.

Introduction: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15-24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action. Purpose: This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats. Results: In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 - 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ-induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing. Discussion: CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively.

Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil.

The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol® ATO 5 (glyceryl palmitostearate) and Labrasol® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol® HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol® 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 µg/cm2/h) as compared with plain 5-FU gel (2.85±1.12 µg/cm2/h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 µg/cm2) as compared with that from the 5-FU plain gel (12.23±3.86 µg/cm2) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations.

RGD-TPGS decorated theranostic liposomes for brain targeted delivery.

The aim of this work was to formulate RGD-TPGS decorated theranostic liposomes, which contain both docetaxel (DTX) and quantum dots (QDs) for brain cancer imaging and therapy. RGD conjugated TPGS (RGD-TPGS) was synthesized and conjugation was confirmed by Fourier transform infrared (FTIR) spectroscopy and electrospray ionisation (ESI) mass spectroscopy (ESI-MS). The theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release study. Biocompatibility and safety of theranostic liposomes were studied by reactive oxygen species (ROS) generation study and histopathology of brain. In-vivo study was performed for determination of brain theranostic effects in comparison with marketed formulation (Docel™) and free QDs. The particle sizes of the non-targeted and targeted theranostic liposomes were found in between 100 and 200nm. About 70% of drug encapsulation efficiency was achieved with liposomes. The drug release from RGD-TPGS decorated liposomes was sustained for more than 72h with 80% of drug release. The in-vivo results demonstrated that RGD-TPGS decorated theranostic liposomes were 6.47- and 6.98-fold more effective than Docel™ after 2h and 4h treatments, respectively. Further, RGD-TPGS decorated theranostic liposomes has reduced ROS generation effectively, and did not show any signs of brain damage or edema in brain histopathology. The results of this study have indicated that RGD-TPGS decorated theranostic liposomes are promising carrier for brain theranostics.

Formulation and delivery of itraconazole to the brain using a nanolipid carrier system.

The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol(®) ATO 5 and Transcutol(®) HP were selected as the lipid phase, and Tween(®) 80 and Solutol(®) HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, -18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery.

Stomach-site specific drug delivery system of clarithromycin for eradication of Helicobacter pylori.

Gellan gum based floating beads containing clarithromycin (FBC) were prepared by iontotropic gelation method for stomach-specific drug delivery against Helicobacter pylori. The scanning electron microscope photograph indicated that prepared beads were spherical in shape with rough outer surface. Formulation variables such as concentrations of gellan, calcium carbonate and drug loading influenced the in vitro drug release characteristics of prepared beads. In vitro release rate of clarithromycin was corrected using first order degradation rate constant which is degraded significantly during the release study in simulated gastric fluid pH 2.0. Further, the absence of interactions between drug and polymer was confirmed by differential scanning calorimetry analysis. Kinetic treatment of the in vitro drug release data with different kinetic equations revealed matrix diffusion mechanism. Prepared beads showed good anti-microbial activity against isolated H. pylori strain. The prepared beads have shown good in vivo floating efficiency in rabbit stomach. The stability studies of beads did not show any significant changes after storage of beads at 40 degrees C/75% relative humidity for 6 months. The preliminary results from this study suggest that floating beads of gellan can be used to incorporate antibiotics like clarithromycin and may be effective when administered locally in the stomach against H. pylori.

Formulation and evaluation of clarithromycin microspheres for eradication of Helicobacter pylori.

The objective of the study was to develop a stomach-specific drug delivery system for controlled release of clarithromycin for eradication of Helicobacter pylori (H. pylori). Floating-bioadhesive microspheres of clarithromycin (FBMC) were prepared by emulsification-solvent evaporation method using ethylcellulose as matrix polymer and Carbopol 934P as mucoadhesive polymer. The prepared microspheres were subjected to evaluation for particle size, incorporation efficiency, in vitro buoyancy, in vitro mucoadhesion and in vitro drug release characteristics. The prepared microspheres showed a strong mucoadhesive property with good buoyancy. The formulation variables like polymer concentration and drug concentration influenced the in vitro drug release significantly in simulated gastric fluid (pH. 2.0). The in vivo H. pylori clearance efficiency of prepared FBMC in reference to clarithromycin suspension following repeated oral administration to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. The FBMC showed a significant anti-H. pylori effect in the in vivo gerbil model. It was also noted that the required amount of clarithromycin for eradication of H. pylori was significantly less in FBMC than from corresponding clarithromycin suspension. The results further substantiated that FBMC improved the gastric stability of clarithromycin (due to entrapment within the microsphere) and eradicated H. pylori from the gastrointestinal tract more effectively than clarithromycin suspension because of the prolonged gastrointestinal residence time of the formulation.

Floating in situ gelling system of acetohydroxamic acid for clearance of H. pylori.

The objective of this study was to develop a novel floating in situ gel system for sustained drug delivery of acetohydroxamic acid (FIGA) for eradication of Helicobacter pylori (H. pylori). The FIGA was prepared by dissolving the different concentration of gellan in deionized water at 80 degrees C. Different concentration of drug and calcium carbonate as floating agents were dispersed with stirring. In vitro results revealed that in situ gelling formulation forms rigid gels instantaneously and floated for longed period time of time in SGF pH 1.2. The formulation parameters, such as concentration of polymer, concentration of calcium carbonate, and concentration of drug, affected the in vitro drug release characteristic significantly. Absence of drug-polymer interaction was confirmed by differential scanning calorimetry analysis. The in vivo H. pylori clearance efficacy of prepared FIGA in reference to acetohydroxamic acid suspension following repeated oral administration to H. pylori-infected Mongolian gerbils was examined by microbial culture method. FIGA showed a significant anti-H. pylori effect in the in vivo gerbil model. It was noted that the required amount of acetohydroxamic acid for eradication of H. pylori was very less in FIGA than in the corresponding acetohydroxamic acid suspension. From the above results, it was concluded that the floating in situ gelling system has feasibility for forming rigid gels in the stomach and eradicated H. pylori from the gastrointestinal tract more effectively than acetohydroxamic acid suspension because of the prolonged gastrointestinal residence time of the formulation.