A multifunctional silk-hyaluronic acid self-healing hydrogel laden with alternatively activated macrophage-derived exosomes reshape microenvironment of diabetic wound and accelerate healing.

The impairment of phenotype switching of pro-inflammatory M1 to pro-healing M2 macrophage induced by hyperglycemic microenvironment often elevates oxidative stress, impairs angiogenesis, and leads to chronic non-healing wounds in diabetic patients. Administration of M2 macrophage-derived exosomes (M2Exo) at wound site is known to polarize M1 to M2 macrophage and can accelerate wound healing by enhancing collagen deposition, angiogenesis, and re-epithelialization. In the present study, M2Exo were conjugated with oxidized hyaluronic acid and mixed with PEGylated silk fibroin to develop self-healing Exo-gel to achieve an efficient therapy for diabetic wounds. Exo-gel depicted porous networked morphology with self-healing and excellent water retention behaviour. Fibroblast cells treated with Exo-gel showed significant uptake of M2Exo that increased their proliferation and migration in vitro. Interestingly, in a diabetic wound model of wistar rats, Exo-gel treatment induced 75 % wound closure within 7 days with complete epithelial layer regeneration by modulating cytokine levels, stimulating fibroblast-keratinocyte interaction and migration, angiogenesis, and organized collagen deposition. Taken together, this study suggests that Exo-gel depict properties of an excellent wound healing matrix and can be used as a therapeutic alternative to treat chronic non-healing diabetic wounds.

Enhanced osseointegration of drug eluting nanotubular dental implants: An in vitro and in vivo study.

Faster and predictable osseointegration is crucial for the success of dental implants, especially in patients with compromised local or systemic conditions. Despite various surface modifications on the commercially available Titanium (Ti) dental implants, the bioactivity of Ti is still low. Thus, to achieve both biological and therapeutic activity on titanium surfaces, surface modification techniques such as titanium nanotubes have been studied as nanotube surfaces can hold therapeutic drugs and molecules. The main aim of the present research work is to study the early osseointegration around the novel Simvastatin drug eluting nanotubular dental implant. In the present research, the titanium nanotubes were fabricated on the screw-shaped dental implant surface and the Simvastatin drug was loaded into the nanotubes using the ultrasonication dip method. In vitro and In vivo studies were carried out on the modified dental implants. In vitro cell culture study reported enhanced osteogenic activity on the drug-loaded nanotube surface implants. The invivo animal studies were evaluated by micro-CT, histopathology, and reverse torque removal analysis methods. The test results showed faster osseointegration with the strong interface on the Simvastatin drug-loaded implant surface at 4 weeks of healing as compared to the control implants.

Fabrication and evaluation of antimicrobial biomimetic nanofiber coating for improved dental implant bioseal: An in vitro study.

BACKGROUND: A weak implant-soft tissue interface may lead to bacterial ingression, breakdown of underlying tissues, and eventually implant failure. This study proposes a surface modification technique of titanium alloy (Ti), using a nano-biopolymer scaffold to enhance soft tissue attachment in dental implants. METHODS: Gelatin (20% w/v) embedded with 10 ± 2 nm silver nanoparticles (AgNPs) was electrospun to form a gelatin electrospun mat (GEM) scaffold, bonded to Ti alloy surface using chemical surface functionalization. Antimicrobial activity of AgNPs was tested against representative Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) at 4, 24, and 48 hours and after embedding in scaffold at 48 hours. Cytotoxicity analysis (MTT assay) was performed using the 3T3 mouse fibroblast cell line at 24 and 72 hours for two groups: control (unmodified Ti disc) and experimental (GEM embedded with AgNPs); and further validated by scanning electron microscopy. RESULTS: The AgNPs-embedded GEM showed good antimicrobial activity at 48 hours, with the AgNPs showing complete (99.99%) inhibition of bacterial colony counts at 24 and 48 hours. Cell viability and proliferation over the GEM modified Ti discs were seen to be significantly increased (P < 0.05) at 72 hours as compared with control. SEM images revealed intimate spreading of fibroblasts, with differentiated cell morphology and pseudopodial processes, indicative of enhanced fibroblastic adhesion, growth, and differentiation over the scaffold. CONCLUSION: Results show good antifouling properties and biocompatibility of the fabricated coating, making it a promising strategy to reduce postoperative infections and peri-implant diseases in Ti dental implants.

Biocompatibility evaluation for the developed hydrogel wound dressing - ISO-10993-11 standards -in vitroandin vivostudy.

Assessment of biocompatibility for the developed wound dressing plays a significant role in translational studies. In the present research work, a wound dressing has been developed using gelatin, hyaluronic acid and chondroitin sulfate using EDC as crosslinker in a specific manner. The characterized hydrogel wound dressing was evaluated for its biocompatibility studies by means of ISO-10993-11 medical device rules and standards. Various parameters like skin sensitization test, acute systemic toxic test, implantation study, intracutaneous reactivity test,in vitrocytotoxicity test and bacterial reverse mutation test, were evaluated and the results demonstrated its safety for the pre-clinical investigation.

Critical Role of Etching Parameters in the Evolution of Nano Micro SLA Surface on the Ti6Al4V Alloy Dental Implants.

The surface of dental implants plays a vital role in early and more predictable osseointegration. SLA (sandblasted large grit and acid-etched) represents the most widely accepted, long-term clinically proven surface. Primarily, dental implants are manufactured by either commercially pure titanium (CP-Ti) or Ti6Al4V ELI alloy. The acid etch behavior of CP-Ti is well known and its effects on the surface microstructure and physicochemical properties have been studied by various researchers in the past. However, there is a lack of studies showing the effect of acid etching parameters on the Ti6Al4V alloy surface. The requirement of the narrow diameter implants necessitates implant manufacturing from alloys due to their high mechanical properties. Hence, it is necessary to have an insight on the behavior of acid etching of the alloy surface as it might be different due to changed compositions and microstructure, which can further influence the osseointegration process. The present research was carried out to study the effect of acid etching parameters on Ti6Al4V ELI alloy surface properties and the optimization of process parameters to produce micro- and nanotopography on the dental implant surface. This study shows that the Ti6Al4V ELI alloy depicts an entirely different surface topography compared to CP-Ti. Moreover, the surface topography of the Ti6Al4V ELI alloy was also different when etching was done at room temperature compared to high temperature, which in turn affected the behavior of the cell on these surfaces. Both microns and nano-level topography were achieved through the optimized parameters of acid etching on Ti6Al4V ELI alloy dental implant surface along with improved roughness, hydrophilicity, and enhanced cytocompatibility.

Preclinical efficacy study of a porous biopolymeric scaffold based on gelatin-hyaluronic acid-chondroitin sulfate in a porcine burn injury model: role of critical molecular markers (VEGFA, N-cadherin, COX-2), gamma sterilization efficacy and a comparison of healing potential to Integra™.

Development of scaffold from biopolymers can ease the requirements for donor skin autograft and plays an effective role in the treatment of burn wounds. In the current study, a porous foam based, bilayered hydrogel scaffold was developed using gelatin, hyaluronic acid and chondroitin sulfate (G-HA-CS). The fabricated scaffold was characterized physicochemically for pre- and post-sterilization efficacy by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA).In-vitrostudies proved that the scaffold promoted cellular proliferation. The efficacy of G-HA-CS scaffold was compared with Integra™ at different time points (7, 14, 21 and 42 days), in a swine second degree burn wound model. Remarkable healing potential of the scaffold was evident from the wound contraction rate, reduction of IL-6, TNF-αand C3. The expression of healing markers TGF-ß1 and collagen 1 revealed significant skin regeneration with regulated fibroblast activation towards the late phase of healing (p< 0.001 at day 21 and 42 vs. control). Expression of Vascular Endothelial Growth Factor A (VEGFA), vimentin and N-cadherin were found to favor angiogenesis and skin regeneration. Mechanistically, scaffold promoted wound healing by modulation of CD-45, cyclooxygenase-2 and MMP-2. Thus, the promising results with foam based scaffold, comparable to Integra™ in swine burn injury model offer an innovative lead for clinical translation for effective management of burn wound.

Fabrication of In Situ Layered Hydrogel Scaffold for the Co-delivery of PGDF-BB/Chlorhexidine to Regulate Proinflammatory Cytokines, Growth Factors, and MMP-9 in a Diabetic Skin Defect Albino Rat Model.

Diabetes mellitus (DM)-associated impairments in wound healing include prolonged inflammation, the overexpression of matrix metalloproteases (MMPs), and low levels of growth factors at the wound site. To this end, a layer-by-layer scaffold (SL-B-L) made of cross-linked silk fibroin and hyaluronic acid is developed to deliver chlorhexidine, an antimicrobial agent and an MMP-9 inhibitor, along with the PDGF-BB protein. SL-B-L exhibited highly porous morphology. Diabetic rats treated with SL-B-L demonstrated an early wound closure, a fully reconstructed epithelial layer by 14 days, and reduced levels of IL-6, TNF-α, TGF-ß1, and MMP-9. Interestingly, SL-B-L treatment increased angiogenesis, the bioavailability of collagen, DNA content, and VEGF-A levels. Furthermore, enhanced keratinocyte-fibroblast interaction along with ordered collagen deposition was observed in SL-B-L-treated rats. Most interestingly, when compared with a clinically used scaffold SEESKIN+, SL-B-L outperformed in promoting wound healing in a diabetic rat model by regulating the inflammation while delivering growth factor and the MMP-9 inhibitor.

Dual functionalized chitosan based composite hydrogel for haemostatic efficacy and adhesive property.

The objective of this study was to devise a dual functionalized chitosan based hydrogel dressing to control haemorrhage/ bleeding. The haemostatic hydrogel was formulated by amalgamation of a definite ratio of quaternized chitosan and phosphorylated chitosan along with tannic acid which acted as adjuvant hemostat and a crosslinker. Additionally, the hydrogel contained poly-Ɛ-lysine to impart the elastic and adhesive properties. The optimized hydrogel exhibited superior haemostatic activity (clotting time, 225 ± 5 s), platelet activation (soluble P-selectin concentration 2098 ± 150.19 ng mL-1), adhesion strength (almost 3 times higher in comparison to Axiostat), higher fluid absorption (approx. 14 times in 12 h) in addition to better mechanical properties, faster coagulation attributes (Prothrombin time, 12.6 s and activated partial thromboplastin time, 30.1 s) and lower proinflammatory potential (almost 3 times lower Tumor Necrosis Factor- α levels and 45 times lower InterLeukin-6 levels at 48 h against control) over marketed chitosan based dressing (clotting time, 300 ± 25 s). Cytotoxicity studies using L929 fibroblasts cells and in-vivo studies using Wistar rats confirmed that the optimized hydrogel was non-toxic, cytocompatible and biocompatible.

Modulating neutrophil extracellular traps for wound healing.

A diabetic microenvironment primes neutrophils for NETosis, a process of formation of neutrophil extracellular traps (NETs) that further degrades the neutrophils and makes them unavailable for the early-stage inflammatory processes. Mechanistically, simple modification of arginine residues of histones to citrulline by peptidylarginine deiminase (PAD4) enzyme is considered to be a prerequisite for NETosis. In fact, under diabetic conditions, an increase in PAD4-mediated NET formation is considered as one of the reasons for impaired wound healing. Therefore, in the present work, an alginate-GelMa (generally recognized as safe category by FDA, USA) based hydrogel scaffold containing a tripeptide (Thr-Asp-F-amidine) that inhibits PAD4 is developed, based on the hypothesis that inhibiting PAD4 enzyme might offer a way to enhance wound healing under diabetic conditions. The scaffolds are thoroughly characterized for their physicochemical and biological properties. Furthermore, neutrophil-scaffold interactions in terms of NETosis ability and release of other related biomarkers are studied. The wound healing ability is evaluated by a cell migration assay. In vivo wound healing efficacy of the developed scaffolds is demonstrated using a diabetic rat model. The results suggest a reduction in NETosis in the presence of a PAD4 inhibitor. Thus, the study demonstrates a novel scaffold system to deliver the PAD4 inhibitor that can be used to modulate NETosis and improve wound healing.

Fabrication and evaluation of gelatin/hyaluronic acid/chondroitin sulfate/asiatic acid based biopolymeric scaffold for the treatment of second-degree burn wounds - Wistar rat model study.

An extracellular matrix (ECM) mimicking architecture was introduced with gelatin glycosaminoglycans like hyaluronic acid and chondroitin sulfate and a triterpenoid using asiatic acid, possessing biodegradable and biocompatible properties that mark the functionality for the treatment of second-degree burn wounds. In the present work, a foam-based scaffold was fabricated and sterilized with gamma radiation at a 2.5 Mrad dose. The scaffolds were further characterized for morphology, swelling, degradation behaviour, release of bioactive components, ATR-FTIR, mechanical, thermal properties and compared with control. In vitro cytocompatibility of the developed scaffold was studied with L929 mouse fibroblast cells and human mesenchymal stem cells based on deoxyribonucleic acid and lactate dehydrogenase assay. Additionally, the developed scaffold was evaluated for its biocompatibility on the Wistar rat to assess any toxicity induced to the animal based on blood biochemistry and histopathology analysis. Finally, we assessed the efficacy of developed foam scaffolds on the second-degree burn wound-induced Wistar rat with a scaffold alone and a scaffold seeded with human bone-marrow-derived mesenchymal stem cells in a wound healing study for 28 d. The wound contraction assay, histopathology, immunohistochemistry analysis and pro-healing marker quantification using hexosamine, hydroxyproline, and pro-inflammatory markers like TNF-α and MMP-2 were carried out and compared with the commercially available wound dressing. The results revealed that foam-based ECM mimic was cytocompatible, biocompatible and biodegradable in 18 ± 3 d in in vivo conditions and the scaffold fostered the process of healing of second-degree burns within 28 d of treatment. The obtained result proved that the scaffold has a potential for clinical settings in second-degree burn wound treatment.

Bacosides Encapsulated in Lactoferrin Conjugated PEG-PLA-PCL-OH Based Polymersomes Act as Epigenetic Modulator in Chemically Induced Amnesia.

The present study demonstrates the epigenetic mechanisms underlying the effect of Bacoside rich extract of Bacopa monniera-a nootropic herb, on scopolamine treated amnesic mice conferred via chromatin modifying enzymes. The focus of the work was to elucidate the modulation of the chromatin modifying enzymes: DNMT1, DNMT3a, DNMT3b, HDAC2, HDAC5 and CPB in scopolamine induced amnesic mice after treatment with bacoside rich extract of Bacopa monniera (BA) and BA encapsulated in lactoferrin conjugated PEG-PLA-PCL-OH based polymersomes (BAN). We observed remarkable difference between the results obtained after the treatment with BA and BAN. Interestingly BAN was found to be more efficient in downregulating DNA methylation and histone chain deacetylation. Scopolamine treatment showed up-regulation of DNMT1 expression in qRT-PCR by 3.14-fold as compared to the control, which was considerably decreased by 1.5-fold after treatment with BA and remarkably decreased 0.11-fold by BAN treatment. Scopolamine treatment up-regulated the expression of DNMT3a by 1.6-fold while for DNMT3b by 3.13-fold. In DNMT3a and DNMT3b the fold change decreased to 0.64 and 0.76 after BA treatment, whereas the BAN treatment further down-regulated to 0.32- and 0.63-fold, respectively. Similarly scopolamine up-regulated HDAC2 and HDAC5 by 3.12 fold and 3.64-fold, respectively. BA treatment reversed the changes by reducing HDAC2 mRNA to 0.89-fold and HDAC5 mRNA 0.83-fold. BAN further reduced expression of HDAC2 further to 0.39-fold and HDAC5 to 0.31-fold. On the other hand scopolamine down-regulated CBP mRNA expression by 0.28-fold and increased by 1.09 after BA treatment. BAN significantly increased the CPB expression by 1.65-fold as compared to BA treatment. These findings were consolidated by DNMT and HDAC enzyme activity assay, methylation in the promoter region of the memory related genes: ARC and BDNF and Dot blot assay for DNA methylation. The percent activity increase of DNMT and HDAC after scopolamine administration was 375.74 and 240.90 respectively. After treatment with BA the downfall in percent activity was observed as 167.99 in DMNT and 130.57 in HDAC. BAN treatment further decreased the percent enzyme activity of DNMT and HDAC significantly by 30.0 and 61.81 respectively. The potency of BAN in reversing the epigenetic changes of scopolamine induced amnesic mouse brain, can be attributed to the brain specific delivery of BA through polymersomes which are able to cross the blood brain barrier (BBB) via receptor mediated endocytosis.

Iontophoretic delivery of lidocaine hydrochloride through ex-vivo human skin.

Background: Iontophoresis is one of the widely used noninvasive and painless transdermal drug delivery technique.Objective: Transdermal delivery of Lidocaine Hydrochloride using continuous and modulated iontophoresis were evaluated across human skin ex-vivo and further assessed for skin tolerance in-vivo in the Swiss albino mice.Methods: Continuous DC was modified into modulated DC by introducing ON-OFF time in continuous DC. Iontophoresis studies were conducted on human skin samples for 60 min.Results: Drug permeation of 2% lidocaine HCl was enhanced in current density-, duty cycle- and time-dependent manner across human skin. The lidocaine HCl concentration obtained with modulated DC and continuous DC iontophoresis were about three-fold and four-fold higher than passive group respectively for all current densities across human skin. Continuous DC iontophoresis was found to be more effective than modulated DC. However, no significant difference was observed in transport of lidocaine HCl between 75% and 100% (continuous) duty cycle at all current density. Further, in-vivo reversibility studies with mice confirmed that modulated iontophoresis was well tolerated by the tissue and the injury caused is transient and reversible.Conclusion: For clinical application, modulated DC iontophoresis with 75% duty cycle at 0.5 mA/cm2 current density would be recommended.

Biosafety of unmodified ultrafine gold particles (AuPs) upon interacting with human blood components before systemic use.

Ultrafine gold particles (AuPs) can be emerged as a good candidate in the field of drug delivery as well as in imaging applications. However, little attention has been paid to detailed study of nanoparticle's interaction with blood components before systemic use. An investigation into the interaction of ultrafine AuPs with blood components is must for its clinical application. In present study, the interaction of ultrafine sized AuPs (2 ±â€¯0.5 nm, 5 ±â€¯1 nm, and 10 ±â€¯2 nm) with blood components and its immunogenic property (pro-inflammatory reaction) was investigated. All three sized AuPs did not cause any significant hemolysis. Plasma coagulation study showed significant increase in Prothrombin time (PT) with International Normalized Ratio (INR) value raised to 1.53 with 10 nm AuPs. Maximum prolongation of activated partial thromboplastin time (APTT) (3.2 s) was seen with 5 &10 nm sized AuPs. Maximum thrombin time (TT) prolongation was seen with 2 nm (18.3s) with the difference of 1.4 s as compared to control. Platelet aggregation was faster in case of 5 & 10 nm sized AuPs. All three sized AuPs exhibited in-vitro C3 complement activation whereas they did not stimulate significant proliferation of peripheral blood mononuclear cells (PBMC). These findings further validate the utility of ultrafine AuPs for in-vivo applications.

Redox Responsive Polymersomes for Enhanced Doxorubicin Delivery.

In the present investigation, the potential of a novel, self-assembled, biocompatible, and redox-sensitive copolymer system with disulfide bond was explored for doxorubicin (DOX) delivery through polymersome nanostructures of ∼120 nm. The polymer system was synthesized with less steps, providing a high yield of 86%. The developed polymersomes showed admirable biocompatibility with high dose tolerability in vitro and in vivo. The colloidal stability of DOX-loaded polymersomes depicted a stable and uniform particle size over a period of 72 h. The cellular internalization of polymersomes was assessed in HeLa and MDA-MB-231 cell lines, where enhanced cellular internalization was observed. The dose-dependent cytotoxicity was observed for DOX-loaded polymersomes by MTT cytotoxicity assay in the above cell lines. The tumor suppression studies were assessed in Ehrlich ascites tumor (EAT) carrying Swiss albino mice, where polymersomes exhibited a 7.16-fold reduction in tumor volume correlated with control and 5.39-fold higher tumor inhibition capacity compared to conventional chemotherapy (free DOX treatment). The developed polymersomes gave safer insights concerning DOX associated toxicities by histopathology and serum biochemistry analysis. Thus, results focus on the potential of redox responsive polymersomes for efficacious and improved DOX therapy with enhanced antitumor activity and insignificant cardiotoxicity which can be translated to clinical settings.

Design, preparation, and evaluation of liposomal gel formulations for treatment of acne: in vitro and in vivo studies.

The study highlights the significance of co-application of bioactive components into liposomal gel formulations and their comparison to azithromycin for treatment of Acne. A Design of Experiments (DoE) approach was utilized to obtain optimized liposomal formulation encapsulating curcumin, with size and zeta potential of ∼100 nm and ∼14 mV, respectively, characterized by DLS, HR-TEM, FESEM, and AFM. The curcumin liposomal dispersion depicted excellent stability over the period of 60 days, which was further converted in gel form using Carbopol. Pharmacokinetics of curcumin-loaded liposomal gel showed that Tmax for curcumin was achieved within 1 h of post application in both stratum corneum and skin, indicating quick penetration of nano-sized liposomes. Stratum corneum depicted Cmax of 688.3 ng/mL and AUC0-t of 5857.5 h × ng/mL, while the skin samples displayed Cmax of 203.3 ng/gm and AUC0-t of 2938.1 h × ng/gm. Lauric acid and azithromycin liposomal gel formulations were prepared as per the optimum parameters obtained by DoE. In antibacterial activity using agar diffusion assay, lauric acid gel formulation revealed ∼1.5 fold improved antibacterial effect than curcumin gel formulation. Interestingly, their co-application (1:1) exhibited significantly enhanced antibacterial effect against both macrolide-sensitive (1.81 versus 1.25 folds) and resistant strains of P. acnes (2.93 versus 1.22 folds) than their individual counterparts. The in vivo studies in rat ear model displayed a ∼2 fold reduction in comedones count and cytokines (TNF-α and IL-1ß) on co-application with curcumin and lauric acid liposomal gel compared to placebo treated group.

Lactoferrin-conjugated pH and redox-sensitive polymersomes based on PEG-S-S-PLA-PCL-OH boost delivery of bacosides to the brain.

In the present study, engineered lactoferrin (Lf)-conjugated pH and redox-sensitive polymersomes derived from the triblock copolymer polyethylene glycol-S-S-polylactic acid-polycaprolactone (PEG-S-S-PLA-PCL-OH) have been used to deliver bacosides to the brain. Bacosides are classified as triterpenoid saponins and are used in Indian Ayurveda for reversal of amnesia; however, no study has extensively demonstrated their efficacy as a nano-formulation in an animal model. The polymer was synthesized by ring opening polymerization of lactide and ε-caprolactone. The nanoparticles obtained by nanoprecipitation showed a core-shell morphology, with an average size of 110 nm, by transmission electron microscopy (TEM). The colloidal stability, hemocompatibility and cytocompatibility of the polymersomes proved their biocompatibility. pH and disulfide linkages in the polymeric chain accelerated the disintegration of the polymersomes at pH 6.6 and at pH 6.6 with glutathione (GSH) in comparison to pH 7.4, supporting their degradation behavior. Supermagnetic iron oxide nanoparticles (SPIONs, 74.99 µg mg-1 polymer) encapsulated into the polymersomes demonstrated their uptake in a mouse model by MRI. Furthermore, bacosides encapsulated in the polymersomes (10% loading) showed significant memory loss reversal in chemically induced amnesic mice, supported by the gene expression profiles of Arc, BDNF and CREB as well as by histopathology.

Effective permeation of 2.5 and 5% lidocaine hydrochloride in human skin using iontophoresis technique.

BACKGROUND: Lidocaine Hydrochloride (HCL) is one of the commonest topical local anesthetic drugs. The permeation of the lidocaine can be enhanced by iontophoresis (IOP). The purpose of this study was to evaluate the permeability of 2.5 and 5% lidocaine permeation in ex vivo human skin using different IOP waveform. METHODS: Continuous and modulated IOP at the current density of 0.5 mA/cm2 were applied across human skin (n = 3) in donor chamber of vertical diffusion cell at 2.5 and 5% lidocaine concentration. High Performance Liquid Chromatography was used to determine lidocaine concentration. RESULTS: Findings revealed that lidocaine concentration increased effectively in a time-dependent manner in both modulated and continuous IOP at 2.5 and 5% lidocaine concentration. Compared to the passive group, the flux of lidocaine with modulated and continuous IOP were higher of about six and ten-fold, respectively. However, no significant difference was observed between continuous and modulated IOP groups at both lidocaine concentrations. At 2.5% lidocaine concentration, the permeation time taken by modulated and continuous IOP to attain therapeutic levels of 142 and 164 µg/cm2 , respectively, was approximately 10 minutes. At 5% lidocaine, the therapeutic permeation of 129 and 147 µg/cm2 , respectively, was achieved at approximately 5 minutes after applying iontophoresis waveform. CONCLUSION: Study shows that modulated IOP can be a promising alternative method in clinical settings aside from continuous IOP. Based on the clinical requirements, IOP can be used at 2.5 and 5% lidocaine concentration depending on need of relatively short or very short onset action.

Evaluation of nano hydrogel composite based on gelatin/HA/CS suffused with Asiatic acid/ZnO and CuO nanoparticles for second degree burns.

In the present work, a hydrogel platform composed of biopolymer gelatin, and glycosaminoglycan's (Hyaluronic acid and Chondroitin sulfate) incorporated with Asiatic acid (a triterpenoid) and nanoparticles (Zinc oxide and Copper oxide) has been designed and developed to find out the efficacy of healing in second degree burn wounds in Wistar rats. The developed hydrogel composite has been characterized by physico-chemical methods such as; SEM, swelling, mechanical strength, degradation and drug release kinetics. Results showed that the morphology of composite scaffolds are porous with maximum water uptake capacity of 1068% and possessed tensile strength of ~0.196 MPa. Anti-microbial evaluation depicted increase in zone of inhibition with hydrogel containing gelatin + ZnO (5.3 ±â€¯0.2 mm in E. coli and 4.9 ±â€¯0.6 mm in S. aureus) and gelatin + CuO (4.8 ±â€¯0.7 mm in E. coli, 3.8 ±â€¯0.3 mm in S. aureus) in comparison to hydrogel composite scaffold. In-vitro cytocompatibility of developed hydrogel composite was assessed in terms of MTT and DNA quantification on L929 fibroblast cells. In-vivo studies for the composite scaffolds were evaluated on Wistar rats after second degree burn wounds were induced and studied for 28 days which showed the significant wound healing activity in comparison to the control (NeuSkin™ and Cotton guaze) in terms of DNA, total protein, hexosamine and hydroxyproline content. Histopathology studies showed the significant progress in re-epithelization, collagen fibers arrangement and angiogenesis in comparison to control. Additionally, a decrease of TNF-α and increase of MMP-2 expression on day 7 of animal experiment support healing. Furthermore, no toxicity was seen with the developed scaffolds suggesting their suitability to use as a wound dressing in second degree burns.

Comparative Assessment of Active Targeted Redox Sensitive Polymersomes Based on pPEGMA-S-S-PLA Diblock Copolymer with Marketed Nanoformulation.

In the present work, polymersomes based on self-assembled, folate-targeted, redox-responsive, ATRP-based amphiphilic diblock copolymer poly(polyethylene glycol)-S-S-polylactide with disulfide linkage were developed for efficient doxorubicin (DOX) delivery and compared with marketed DOXIL nanoformulation. The polymersomes formulation was optimized by quality by design approach providing monodisperse nanostructures of ∼110 nm and enhanced DOX loading of ∼20%. Polymersomes showed excellent stability as per the ICH guidelines over the extended storage period of 3 months. The in vitro drug release profile confirmed the redox sensitive behavior of polymersomes providing ∼80% drug release in endosomal pH 5 with 10 mmol GSH as compared to ∼20% release at pH 7.4. The targeted polymersomes achieved enhanced cellular internalization in folate receptor overexpressing cell lines, MDA-MB-231 and HeLa, providing ∼24% higher tumor reduction than DOXIL in Ehrlich ascites tumor bearing Swiss albino mice.