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Keloids are manifestations of abnormal wound repair with unresolved clinical complications. An effective therapeutic regimen has not been established for keloids, and current strategies are plagued by problems such as recurrence and side effects. Keloids, being a human-specific dermal fibroproliferative disorder are characterized by an excessive accumulation of extracellular matrix (ECM), thickened basement membrane, unregulated expression of matrix metalloproteases, growth factors, and cytokines. The internal milieu in a keloid bears a strong resemblance to a tumor with both exhibiting striking similarities with respect to tissue environment and unregulated vasculature. Abnormal angiogenesis manifested by an imbalance between proangiogenic and antiangiogenic factors has been recognized as a 'common denominator' underlying many pathological conditions. However, such an imbalance has not been investigated in keloids. In this study, the angiogenic imbalance in keloids was explored with reference to circulating and tissue level expression of vascular endothelial growth factor (VEGF) and endostatin/collagen XVIII. It was observed that VEGF levels were upregulated and endostatin levels were downregulated in keloid patients in comparison to normal controls in both sera and tissue. Hence, antiangiogenic therapeutics based on endostatin in combination with current curative strategies as in tumors would present a scope for the effective management of keloids. [ABSTRACT FROM AUTHOR]

Background: The eukaryotic elongation factor, EEF1A2, has been identified as an oncogene in various solid tumors. Here, we have identified a novel function of EEF1A2 in angiogenesis., Methods: Chick chorioallantoic membrane, tubulogenesis, aortic ring, Matrigel plug, and skin wound healing assays established EEF1A2's role in angiogenesis., Result: Higher EEF1A2 levels in breast cancer cells enhanced cell growth, movement, blood vessel function, and tubule formation in HUVECs, as confirmed by ex-ovo and in-vivo tests. The overexpression of EEF1A2 could be counteracted by Plitidepsin. Under normoxic conditions, EEF1A2 triggered HIF1A expression via ERK-Myc and mTOR signaling in TNBC and ER/PR positive cells. Hypoxia induced the expression of EEF1A2, leading to a positive feedback loop between EEF1A2 and HIF1A. Luciferase assay and EMSA confirmed HIF1A binding on the EEF1A2 promoter, which induced its transcription. RT-PCR and polysome profiling validated that EEF1A2 affected VEGF transcription and translation positively. This led to increased VEGF release from breast cancer cells, activating ERK and PI3K-AKT signaling in endothelial cells. Breast cancer tissues with elevated EEF1A2 showed higher microvessel density., Conclusion: EEF1A2 exhibits angiogenic potential in both normoxic and hypoxic conditions, underscoring its dual role in promoting EMT and angiogenesis, rendering it a promising target for cancer therapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The dysregulated energy metabolism in white adipose tissues results in derangement of biological signaling resulting in obesity. Lack of vascularization in these white adipose tissues is one of the major reasons for dysregulated energy metabolism. Not much work has been done in this direction to understand the role of angiogenesis in white adipose tissue metabolism. In the present study, we evaluated the effect of angiogenic modulator in the metabolism of white adipocyte (WAC). Bioactive Apigenin was selected and its angiogenic ability was studied. Apigenin was shown to be highly proangiogenic hence the effect of Apigenin on de novo and trans-differentiation of WAT was studied. Apigenin showed enhanced de novo differentiation and trans-differentiation of mouse WAC into brown-like phenotype. To understand the effect of Apigenin on adipose tissue vasculature, coculture studies were conducted. Cross talk between endothelial cell and adipocytes were observed in coculture studies. Gene expression studies of cocultured cells revealed that browning of WAC occurred by triggering the expression of Vascular endothelial growth factor A. The study provides a new insight for inducing metabolic shift in WACs by modulation of angiogenesis in WAC microenvironment by the upregulation of PRDM16 cascade to trigger browning for the treatment of obesity., (© 2022 Wiley Periodicals LLC.)

Scars occur as a result of fibrosis after tissue damage or surgery and reports suggest that excessive Transforming growth factor-β (TGF-β) activity during the process of wound healing leads to progressive fibrosis. Decorin is an extracellular matrix (ECM) protein which regulates collagen fibrillogenesis. However, targeted delivery and effective protein therapy remains a challenge owing to degradation byproteases. Hence, we aimed to deliver Decorin in a sustainable mode for the reduction of TGF-β levels and subsequent scar formation. Herein, we have fabricated PCL-Gelatin bio-mimetic scaffolds to optimize the bio-activity and provide localized delivery of recombinant Decorin. The degradation and drug release patterns reveals that this biomaterial is biodegradable and offers sustained release of the recombinant Decorin. Decorin loaded nanofiber displayed lower adhesion and proliferation rates in in-vitro conditions. Moreover, Decorin loaded scaffolds demonstrated morphological changes in cells, specifically targeting the myofibroblast. The expression of TGF-β was also scrutinized to understand the effect of Decorin loaded nanofibers. Besides, in the in-vitro fibrotic model, Decorin loaded nanofibers efficiently reduced the expression of ECM related proteins. Therefore, we report the sustained delivery of the recombinant Decorin from nanofiber dressing to potentially obstruct scar formation during the process of wound healing., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Scaffold proteins coordinate multiple signalling pathways by integrating various proteins but the role of these proteins in neuronal pathways remains to be elucidated. The present study focused to evaluate the expression of the scaffold protein CULLIN2 in neuronal cells., Methods: The neuronal precursor cell line N2A was differentiated to neurons in-vitro with retinoic acid and biochemical assays were used to understand the gene expression profiling of CULLIN2. Moreover, neddylation inhibitor MLN4924 was used to inhibit the activity of CULLIN2 and the downstream substrates were validated. Finally, the role of CULLIN2 in nerve regeneration was evaluated in an in vivo zebrafish model., Results: Experimental data showed that the neuronal cells N2A have lower expression of CULLIN2 compared to skin cell lines (HaCaT and A431) and inactivation with the neddylation inhibitor resulted in cell death. Furthermore differentiating the neural precursor cell line into neurons with retinoic acid enhanced the expression of CULLIN2. Examining downstream signalling molecules with the neddylation inhibitor illuminates that MLN4924 treatment influences the cytokine signalling cascade (JAK-STAT) in neuronal cells. Moreover, for the first time, we show that the ubiquitin ligase protein CULLIN2 is perturbed in neural regeneration. Expression profile of CULLIN2 was significantly decreased in response to a nerve injury in Zebra fish and as the nerve regenerates there is corresponding reduction in the mRNA levels., Conclusion: During differentiation CULLIN2 is upregulated whereas during regeneration there is significant downregulation. Thus, our findings reveal a crucial role of the scaffold protein CULLIN2 in nerve differentiation and regeneration which can be vital for the treatment of nerve injury., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rare earth lanthanum oxide nanoparticle reinforced collagen biomatrix that elicited the endothelial cell activation to promote angiogenesis for biomaterial integration was developed and evaluated in the present study. The structural integrity of collagen was not compromised on crosslinking of lanthanum oxide nanoparticle to collagen biomolecule. As-synthesised collagen biomatrix was shown to have improved mechanical strength, a lesser susceptibility to proteolytic degradation and good swelling properties. Superior cytocompatibility, hemocompatibility and minimal ROS generation was observed with Lanthanum oxide nanoparticle reinforced collagen bio matrix. The Lanthanum oxide nanoparticle reinforced collagen bio matrix elicited endothelial cell activation eliciting pro-angiogensis as observed in tube formation and aortic arch assays. The bio-matrix promoted the infiltration and proliferation of endothelial cells which is an unexplored domain in the area of tissue engineering that is very essential for biomaterial integration into host tissue. The wound healing effect of Lanthanum oxide nanoparticle stabilized collagen showed enhanced cell migration in vitro in cells maintained in Lanthanum oxide nanoparticle reinforced collagen bio matrix. The study paves the way for developing rare earth-based dressing materials which promoted biomatrix integration by enhancing vascularisation for tissue regenerative applications in comparison with traditional biomaterials., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The highly complex pathophysiology of the wound micro-environment demands the development of a multi-faceted system which would enhance the wound healing cascade. Incorporation of nanotechnology in wound therapeutics has opened up new avenues to tourment the diseased condition. Amongst the various types of nanoparticles molybdenum oxide nanoparticles posses various inherent properties that makes it a versatile material to be used in healing. Incorporation of Molybdenum nanoparticles into collagen scaffolds would provide a synergistic and sequential healing process ensuring the formation of a fully functional tissue., Materials and Methods: The physico-chemical characterization of the synthesized materials were done using SEM and FT-IR techniques. The bicompatibility and cell proliferation were tested using HaCaT cell lines. Pro-angiogenic ability of the scaffold was tested using CAM assay and Chick aortic arch assay. Finally the in-vivo wound healing ability of the material was tested by creating wound of about 6 cm 2 on the dorsal side of Wistar rats and observed for about 21 days., Results: The characterization of the scaffold revealed the presence MoO 3 nanoparticles and their structural integrity within the scaffold. The synthesized MoO 3 -collagen nanocomposite was found to be biocompatible and hemocompatible. The in-vitro studies demonstrated that the MoO 3 -collagen scaffold significantly increased the cell adhesion and migration to nearly 2 fold. The MoO 3 embedded collagen sheets synergistically favoured neovascularization and re-epithelization,which would potentially enhance therapeutic efficiency of the scaffold. The nanocomposite also encouraged results in in-vivo analysis, the Wistar rats treated with MoO 3 -collagen scaffolds showed complete healing in about 15 days., Conclusion: The fabricated MoO 3 -collagen scaffold was found to play an important role in all major events of wound healing such as adhesion, migration, proliferation and angiogenesis. The in-vivo healing assay also proved that the healing rate of animals treated with the samples was comparatively faster. Further research using various trace elements would open up promising avenues in healing therapeutics., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Electrospinning, a recent fast-emerging technique highly applicable in the production of nanofibers has gained vast recognition owing to its explicit applications in various domains. Amongst which, the production of nanoscaffolds for wound healing applications has been focused recently due to advantages over conventional wound healing methods. In the present research, a composite nanoscaffold comprising SBA-15 (Santa Barbara Amorphous), amine functionalized SBA-15 polycaprolactone (PCL) and curcumin was investigated for its potentiality in wound healing therapeutics. The high biocompatibility and cell adhesion of amine functionalized SBA-15 and the widely explored antimicrobial properties of curcumin added benefit for the wound healing target. The prepared highly interconnected electrospun fibers with porous structure were characterized through various studies such as FTIR, XRD, SEM and EDAX. Further, antibacterial studies against both Gram positive (Bacillus subtilis) and Gram negative (Escherichia coli) strains revealed an improved zone of inhibition. Major invitro studies such as cell migration, proliferation, bio-compatibility was experimented through cell adhesion and live and dead assay using Swiss 3T6 cell lines. In vivo studies on female Wister rats using the fabricated nanofibers incorporated with curcumin and amine functionalized SBA-15 showed 99% scar-less wound healing within 21 days. Re-epithelization of tissue, collagen deposition and formation of granulation tissue were observed from the results of Hematoxylin-Eosin and Masson's tri-chrome staining. From the observations, it can be concluded that the fabricated nanoscaffold could be an effective substrate for wound healing therapeutics., (Copyright © 2021. Published by Elsevier B.V.)

Objective: The study is aimed to verify the possibility of using humanized alternatives to fetal bovine serum (FBS) such as umbilical cord blood plasma (CBP) and AB + plasma to support the long-term growth of mesenchymal stromal cells (MSCs) derived from the umbilical cord. We hypothesized that umbilical CBP would be a potential substitute to FBS, especially for small scale autologous clinical transplantations., Methods: The MSCs were cultured for six consecutive passages to evaluate xeno-free media's ability to support long-term growth. Cell proliferation rates, colony-forming-unit (CFU) efficiency and population doublings of expanded MSCs, were investigated. Ex vivo expanded MSCs were further characterized using flow cytometry and quantitative PCR. The impact of cryopreservation and composition of cryomedium on phenotype, viability of MSC was also assessed., Results: Our results on cell proliferation, colony-forming unit efficiency suggested that the expansion of the cells was successfully carried out in media supplemented with humanized alternatives. MSCs showed lower CFU counts in FBS (~ 25) than humanized alternatives (~ 35). The gene expression analysis revealed that transcripts showed significant differential expression by two to three folds in the FBS group compared with MSCs grown in medium with humanized alternatives (p < 0.05). In addition, MSCs grown in a medium with FBS had more osteogenic activity, a signature of unwanted differentiation. The majority of ex vivo expanded MSCs at early and late passages expressed CD44 + , CD73 + , CD105 + , CD90 + , and CD166 + in all the experimental groups tested (~ 90%). In contrast to the other MSC surface markers, expression levels of STRO-1 + (~ 21-10%) and TNAP + (~ 29-11%) decreased with the increase in passage number for MSCs cultured in a FBS-supplemented medium (p < 0.05)., Conclusion: Our results established that CBP supported culture of umbilical cord tissue-derived MSCs and is a safer Xeno free replacement to FBS. The use of CBP also enables the storage of umbilical cord tissue derived MSCs in patient-specific conditions to minimize adverse events if cells are delivered directly to the patient., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The discovery of cardiac progenitor cells (CPCs) has raised expectations for the development of cell-based therapy of the heart. Although cell therapy is emerging as a novel treatment for heart failure, several issues still exist concerning an unambiguous definition of the phenotype of CPC types. There is a need to define and validate the methods for the generation of quality CPC populations used in cell therapy applications. Considering the critical roles of cardiac cell progenitors in cellular therapy, we speculate that long term culture might modulate the immunophenotypes of CPCs. Hence, a strategy to validate the isolation and cell culture expansion of cardiac cell populations was devised. Isolation of three subpopulations of human CPCs was done from a single tissue sample using explant, enzymatic isolation, and c-kit + immunomagnetic sorting methods. The study assessed the effects of ex vivo expansion on proliferation, immunophenotypes, and differentiation of CPCs. Additionally, we report that an explant culture can take over 2 months to achieve similar cell yields, and cell sorting requires a much larger starting population to match this expansion time frame. In comparison, an enzymatic method is expected to yield equivalent quantities of CPCs in 2-3 weeks, notably at a significantly lower cost, which may intensify their use in therapeutic approaches. We determined that ex vivo expansion caused changes in cellular characteristics, and hence propose validated molecular signatures should be established to evaluate the impact of ex vivo expansion for a safe cell therapy product., (© 2020 Wiley Periodicals LLC.)

Wound healing is a complex process which requires appropriate structural support for restoration of tissue continuity and function. Collagen can act as a template for cellular activities but poor physico-chemical properties necessitates the stabilization of collagen without impairing its structure and function. This study investigates the effect of magnesium ascorbyl phosphate (MAP) on collagen with reference to physico-chemical properties. Incorporation of MAP enhanced the rate of collagen fibrillation signifying increased interaction at reduced time interval. MAP did not induce any changes in the secondary structure of collagen while there was an increase in shear viscosity with increase in shear stress at different shear rate. MAP stabilized collagen film exhibited higher denaturation temperature and showed an increase in Young's Modulus when compared with that of collagen film. In vivo studies showed complete wound closure on day 16 in case of stabilized collagen film. Mechanical properties of healed skin revealed that MAP collagen film treated rat skin completely regained its properties similar to that of normal skin thereby making them a potential candidate for wound healing application., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chronic periodontal disease affect the tissues supporting around the teeth like gingival tissue, connective tissue, alveolar bone and periodontal ligaments. Hitherto, periodontal treatment was targeted to selectively repopulate the defect site with cell that has capability to regenerate lost tissue by promoting the concept of guided tissue regeneration but it requires second surgery due to non- biodegradability. The use of polymeric biodegradable nanofibrous coated scaffold that have the ability to deliver bioactives required for regeneration to occur is relatively a newer concept. The functionalization of polymeric scaffold with Bromelain and magnesium doped hydroxyapatite nanoparticle enhanced the mechanical, physico-chemical, thermal and biological properties of the scaffold by imitating the intricate extracellular matrix (ECM) architecture which provided the necessary bioactive cues that offered control over cellular functions by showing antibacterial potential, hemocompatibility and increasing the proliferation and migration rate in vitro. In addition, in ovo chicken chorioallantoic membrane assay and ex vivo aortic ring assay confirmed the efficacy of the developed scaffold by encouraging angiogenesis required for maintaining its viability after implanting onto the infected area. Further, the scaffold positively interacted with the host and actively contributed to the process of tissue regeneration in vivo in Wistar rat model., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Fabricating and designing a scaffold is a complex and highly challenging process in the current scenario. The present study deals with the design and fabrication of electrospun Santa Barbara Amorphous (SBA)-15-incorporated polyvinyl alcohol (PVA) with curcumin, which can be used as a biomimetic nanoscaffold for skin tissue engineering. Curcumin was selected due to its effective anti-microbial and anti-inflammatory properties. SBA-15 was selected for its characteristic drug-carrying potential. Fourier transform infrared spectroscopy and x-ray diffraction characterizations of the fabricated nanofiber demonstrated the interaction of PVA, SBA-15 and curcumin. The scanning electron microscopy results depicted that the nanofiber was highly interconnected with a porous structure mimicking the extracellular matrix. The nanofibrous scaffold showed a higher percentage of cell migration, proliferation, cytocompatibility and biocompatibility with absence of cytotoxicity which was evidenced from the results of MTT assay, cell adhesion and live/dead assay using HaCaT cells. The results of the anti-bacterial test depicted that the synthesized nanofiber forms a potent material for skin wound-healing therapeutics. The in vitro drug release study performed over a period of 80 h revealed a sustained release pattern of curcumin from the SBA-15-incorporated PVA nanofiber. Finally, the in vivo results confirmed that SBA-15-incorporated PVA nanofiber with curcumin showed efficient wound-healing activities.

Conventional cancer therapies possess a plethora of limitations which led to the awakening of nanotechnology and nanomedicine. However, technological success is widely dependent on complete understanding of the complexity and heterogeneity of tumor biology on one hand and nanobiointeractions associated with challenges of synthesis, translation, and commercialization on the other. The present study therefore deals with one such targeted approach aiming at synthesizing, characterizing, and understanding the efficacy of molybdenum oxide nanoparticles. The phase structure, morphology, and elemental composition of the synthesized nanoparticles were characterized using Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The cytotoxicity studies revealed that the IC 50 vales of molybdenum trioxide (MoO 3 ) particles against skin cancer cells (melanoma and non-melanoma) were around 200-300 μg. The nanoparticles were found to induce mitochondrial-mediated apoptosis driven by the apoptotic genes such as BAX and Bcl 2 . Molybdenum being a cofactor for the majority of metabolic enzymes could have triggered the selective internalization of the nanoparticles which in turn could have modified the granularity of the cytoplasm and subsequently lead to mitochondrial-mediated apoptosis. Further, the anti-angiogenic property of MoO 3 nanoparticles was corroborated using Chick chorioallantoic membrane (CAM) assay and aortic ring assay. Taken together , unraveling the role of MoO 3 nanoparticles in cancer and angiogenesis opens up venues for nano biological intervention of selective cancer cell targeting with minimal damage to the normal cells using natural trace elements that are generally known to influence various metabolic enzymes.

Drug delivery through nanotechnological approaches has predominantly gained significance owing to the enhanced bioavailability, stability and targeted sequel. Multiple drug delivery is also on its stride to achieve holistic therapeutic regime. In our quest for such a treatment for cancer we selected two phytochemicals namely resveratrol (RS) and ferulic acid (FA) that have gained wide attention in the field of medicine due to their array of properties. Albeit their multifaceted application their therapeutic potential is mired due to its physicochemical instability and low bioavailability. Therefore, in the present study combinatorial effect of these compounds in cancer therapeutics have been scrutinized by fabricating chitosan nanoparticle loaded polycaprolactone nanofibers for delivering RS and FA. The materials were physico-chemical characterized. The nanoparticle incorporation within the nanofibers was corroborated through FITC tagging. The anti-cancer effect of drug loaded nanofibers were studied using A431 cells which displayed 30% and 50% reduction in the cell viability when treated with nanoparticles and nanofibrous scaffold. In congruence, the anti-angiogenic potential of the scaffold was elucidated using Chick chorioallantoic membrane assay and aortic ring assay. Thus, the nanofibrous delivery system opens up new venue in the field of cancer therapeutics with reduced side effects and efficient cancer targeting., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, gelatin-polyethylenimine blend nanofibers (GEL/PEI) were fabricated via electrospinning with different ratios (9:1, 6:1, 3:1) to integrate the properties of both the polymers for evaluating its biomedical application. From scanning electron microscopy, the average diameter of blend nanofibers (265 ± 0.074 nm to 340 ± 0.088 nm) was observed to be less than GEL nanofibers (403 ± 0.08 nm). The incorporation of PEI with gelatin resulted in improved thermal stability of nanofibers whereas the Young's modulus was observed to be higher at 9:1 ratio when compared with other ratios. The in vitro studies showed that the GEL/PEI nanofibers with 9:1 ratio promoted better cell adhesion and viability. GEL/PEI nanofibers with 9:1 and 6:1 showed hemolysis within the permissible limits. From the results, it could be interpreted that GEL/PEI nanofibers with 9:1 ratio proved to be a better scaffold thereby making them a potential candidate for tissue engineering applications.

The present study describes the fabrication of collagen reinforced with praseodymium-cobaltite nanoparticles for wound healing applications. Praseodymium-cobaltite nanoparticles (PCNP) reinforced with collagen resulted in an increased thermal stability and decreased proteolytic susceptibility to collagen. Circular dichroism spectroscopy and ATR-FTIR (attenuated total reflection Fourier transform infrared) spectroscopy analyses confirm the intact structural integrity of the collagen sheets after cross-linking with praseodymium-cobaltite nanoparticles. Cross-linked collagen has shown to possess biocompatibility, less protein adsorption behavior, and hemocompatibility, which are the desirable properties of a wound dressing material. The nanoparticle cross-linked collagen sheets provided a proper matrix elasticity that promotes mesenchymal stem cell attachment and angiogenesis. Further, the scaffold promoted tube formation in endothelial cells. The enhancement of angiogenesis is considered to be brought about by the therapeutic potential of nanoparticle formulation. Praseodymium-cobaltite nanoparticle cross-linking increased the ductility of collagen sheets for the pro-angiogenic and stem cell differentiation ability. Also, the praseodymium-cobaltite cross-linked collagen sheets have been shown to induce a mild level of ROS (reactive oxygen species) generation in the DCFH-DA (2',7'-dichlorodihydrofluorescein diacetate) assay, which is beneficial for angiogenesis as well as wound healing. This study paves the way for exploring the therapeutic potential of rare-earth-based nanoparticles for tissue engineering applications as an alternative for traditional wound healing materials.

Nerve injuries are often debilitating as its regeneration occurs in a slow and laborious manner. Remediation of nerve injury is a colossal task as functional restoration in larger gaps seldom occurs due to the complex nerve regeneration mechanism. A nanofiber-based graft material has been fabricated to provide topographical and biochemical cues to encourage neural differentiation. Laminin plays a crucial role in supporting peripheral nerve regeneration and hence aligned polyvinyl cinnamate nanofibers surface-conjugated with laminin-derived cell-adhesion peptides have been fabricated to improve selective neural adhesion and regeneration. Further, triiodothyronine has been encapsulated within the nanofibers enabling its sustained release so as to bolster regeneration and reinstate the lost functionality to the damaged nerve. The fabricated nanofibers were characterized for its physicochemical, morphological, and topographical properties. Nanofibers were biocompatible, improved cell adhesion rate, and illustrated favourable interaction with cells. Gene expression (showed 9.5 and 4.1 fold increase in β-tubulin and MAP 2 expression, respectively) and protein expression (immunofluorescence, flow cytometry, and western blot) studies confirmed the positive influence of the scaffold over cell differentiation. The studies were extrapolated to adult zebrafish model with a surgical incision in posterior lateral line. The biocomposite treated group showed earlier functional restoration of the nerve compared with control groups detected by touch-evoked response. Thus, the combination of aligned nanofibers providing topographical cue, along with the peptides and triiodothyronine serving as biochemical cues, has a robust potential to restore functionality to the injured nerve, thereby opening avenues for fabrication of regenerative nerve grafts., (© 2019 John Wiley & Sons, Ltd.)

Angiogenesis is a vital component of the orchestrated wound healing cascade and tissue regeneration process, which has a therapeutic prominence in treatment of ischemic vascular diseases and certain cardiac conditions. Based on its eminence, several strategies using growth factors have been studied to initiate angiogenesis. However, growth factors are expensive and have short half-life. In this work, sustained release of triiodothyronine, which plays a crucial role in stimulating growth factors and other signaling pathways that are instrumental in initiating angiogenesis, has been attempted through electrospun polycaprolactone nanofibers. This delivery system enabled the slow and sustained delivery of triiodothyronine into the micro-environment, reducing seepage of excess into systemic circulation and eliminating the necessity of repeated dosage forms. It was observed that triiodothyronine-incorporated nanofibers exhibited favorable interaction with cells (phalloidin staining of actin filaments) and also enhanced the rate of endothelial proliferation, migration, and adhesion. The angiogenic potential of these nanofibers was further corroborated through chorioallantoic membrane and rat aortic ring assay (demonstrating cell sprouting area of 3.3 ± 0.71 mm 2 compared to 1.2 ± 0.01 mm 2 in control). The nanofiber matrix thus fabricated demonstrated a vibrant therapeutic potential to induce angiogenesis. Triiodothyronine also plays a significant role in wound healing independent of initiating angiogenesis. This further substantiates the positive impact of this delivery system as a dressing material for chronic wound therapeutics, ischemic vascular diseases, and certain cardiac conditions.

A xeno-free method for ex vivo generation of red blood cells (RBCs) is attempted in order to replicate for large-scale production and clinical applications. An efficient milieu was formulated using injectable drugs substituting the animal-derived components in the culture medium. Unfractionated mononuclear cells isolated from human umbilical cord blood were used hypothesizing that the heterogeneous cell population could effectively contribute to erythroid cell generation. The strategy adopted includes a combination of erythropoietin and other injectable drugs under low oxygen levels, which resulted in an increase in the number of mature RBCs produced in vitro. The novelty in this study is the addition of supplements to the medium in a stage-specific manner for the differentiation of unfractionated umbilical cord blood mononuclear cells (MNCs) into erythropoietic lineage. The erythropoietic lineage was well established by day 21, wherein the mean cell count of RBCs was found to be 21.36 ± 0.9 × 10 8 and further confirmed by an upregulated expression of CD235a + specific to RBCs. The rationale was to have a simple method to produce erythroid cells from umbilical cord blood isolates in vitro by mitigating the effects of multiple erythroid-activating agents and batch to batch variability.

Cancer nanomedicine has emerged as a revolution in the last decade opening up promising strides for the cancer treatment. The major challenge in these therapeutic approaches resides in the failure of clinical trials owing to the immunological cancer microenvironment. Therefore, the success of next generation nanomedicine depends on tunable physicochemical nanomaterial design and corresponding clinical trials by integrating targeted delivery with mitigated toxicity. The present study deals with the fabrication of nanofibrous scaffold impregnated with molybdenum nanoparticles for targeted skin cancer therapeutics. Molybdenum oxide, a transitional metal oxide is gaining rapid importance due to its vital role in cellular and molecular metabolism. Polycaprolactone nanofibers were chosen as a matrix to localize the nanoparticles topically facilitating selective apoptosis of the tumor cells over the normal cells with mitigated side effects. The scaffold was designed to tailor the physicochemical, mechanical and biological suitability for skin cancer (melanoma and non melanoma). The designed scaffold was found to reduce more than 50% cell viability of the cancer cells selectively through apoptosis as confirmed using AO/PI staining and the probable mechanism could be attributed to the induction of mitochondria dependent apoptosis as observed by JC1 dye staining. In-vivo trials in zebra fish were found to reduce cancer progression by more than 30% in 14 days. The fabricated molybdenum trioxide nano constructs not only serve as tunable targeted systems but also open venues capable of ferrying chemotherapeutic drugs sparing normal cells alleviating the trauma due to side effects., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The major loss of myocardial tissue extracellular matrix after infarction is a serious complication that leads to heart failure. Regeneration and integration of damaged cardiac tissue is challenging since the functional restoration of the injured myocardium is an incredible task. The injured micro environment of myocardium fails to regenerate spontaneously. The emergence of nano-biomaterials would be a promising approach to regenerate such a damaged cardiomyocytes tissue. Here, we have fabricated a dual bioactive embedded nanofibrous cardiac patch via coaxial electrospinning technique, to mimic the topographical and chemical cues of the natural cardiac tissue. The proportion and the concentration of the polymers were optimized for tailored delivery of bioactives from a spatio-temporally designed scaffold. The functionalization of polymeric core shell nanofibrous scaffold with dual bioactives enhanced the physico-chemical and bio-mechanical properties of the scaffolds that has resulted in a 3-dimensional topography mimicking the natural cardiac like extracellular matrix. The sustained delivery of bioactive signals, improved cell adhesion, proliferation, migration and differentiation could be attributed to its highly interconnected nanofibrous matrix with good extended morphology. Further, the expression of cardiac specific markers were found to increase on investigation of mRNA by real time PCR studies and proteins by immunofluorescence and western blotting techniques, confirming cell - biomaterial interactions. Flow cytometry analysis authenticated a potent mitochondrial membrane potential of cells treated with nanocomposite. In addition, in ovo studies in chicken chorioallantoic membrane assay confirm the efficacy of the developed scaffold in inducing angiogenesis required for maintaining its viability after transplantation onto the infarcted zone. These promising results demonstrate the potential of the composite nanofibrous scaffold as an effective biomaterial substrate for cardiac regeneration providing cues for development of novel cardiac therapeutics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A biomimetic Zein polydopamine based nanofiber scaffold was fabricated to deliver bone morphogenic protein-2 (BMP-2) peptide conjugated titanium dioxide nanoparticles in a sustained manner for investigating its osteogenic differentiation potential. To prolong its retention time at the target site, BMP-2 peptide has been conjugated to titanium dioxide nanoparticles owing to its high surface to volume ratio. The effect of biochemical cues from BMP-2 peptide and nanotopographical stimulation of electrospun Zein polydopamine nanofiber were examined for its enhanced osteogenic expression of human fetal osteoblast cells. The sustained delivery of bioactive signals, improved cell adhesion, mineralization, and differentiation could be attributed to its highly interconnected nanofibrous matrix with unique material composition. Further, the expression of osteogenic markers revealed that the fabricated nanofibrous scaffold possess better cell-biomaterial interactions. These promising results demonstrate the potential of the composite nanofibrous scaffold as an effective biomaterial substrate for bone regeneration., (Copyright © 2017 John Wiley & Sons, Ltd.)

Regeneration of the central and peripheral nervous system is challenging since the functional restoration of injured nerves is an incredible task. The fabrication of an ideal nerve guide that fulfills the requirement to regenerate nerve tissue is a herculean challenge requiring a combination of both biochemical and topographical cues. The present study explores the combinatorial effect of aligned nanofibers and the regulated delivery of triiodothyronine and retinoic acid on nerve regeneration. A sequential release mechanism is adopted in fabricating the nanofiber scaffold, with triiodothyronine incorporated into the nanofiber shell ensuring its prior release, followed by retinoic acid (entrapped within zein nanoparticles) from the core. The composite nanofibers thus fabricated possess excellent mechanical, physical and thermal properties and good topographical morphology and were highly biocompatible. The nanofibers were scrutinized for their efficacy in stimulating differentiation to a neuronal phenotype. The elongation factor (E-factor) of the neural cells had doubled in the bioactive incorporated composite compared to other scaffolds, as observed on phalloidin staining of their cytoskeleton, which endorsed enhanced neural differentiation on the fabricated nanofiber scaffold. There was a significant increase in the expression of neural-lineage specific markers on investigation of mRNA by real time PCR, showing a 10 fold increase in the gene expression of β-III-tubulin, a 5.5 fold increase for microtubule associated protein 2 gene and 3.5 fold for neurofilament M gene in the cells cultured over bioactive incorporated aligned nanofiber composites. Similarly protein expression was analyzed by immunofluorescence and flow cytometry studies, which showed an increase in the expression of β-III-tubulin in the composite nanofiber. This corroborates that neuronal differentiation is enhanced by the aligned nanotopography and spatio-temporal delivery of triiodothyronine and retinoic acid, opening avenues for nerve regenerative graft fabrication.

Polymers from renewable resources are attractive for various industrial and biomedical applications owing to their compatibility, degradability, ease of use and availability. Rapid progress in the development of nanotechnology has improved the characteristic features of polymers in composite materials by reinforcing the nanosized particulates during fabrication. In this study, we have attempted to incorporate metal oxide nanoparticles into polymeric nanofibers in order to enhance the overall properties of the composite scaffold. The thermal stability of a TiO 2 nanoparticle-impregnated zein-polydopamine-based nanofibrous scaffold was investigated, and its potential as a suitable wound dressing material was demonstrated. Further, the influence of nanotopographic structure on improved adhesion, proliferation and migration of cells was ascertained through in vitro assays. The constructive results obtained were well corroborated with the in vivo excisional wound healing experiment. Thus, the competence of the prepared nanofibrous scaffold was examined both in vitro and in vivo and demonstrated to be an alternative, cost-effective biomaterial for skin tissue engineering applications.

The physiological and pathological complexity of the wound healing process makes it more challenging to design an ideal tissue regeneration scaffold. Precise scaffolding with high drug loading efficiency, efficient intracellular efficacy for therapeutic delivery, minimal nonspecific cellular and blood protein binding, and maximum biocompatibility forms the basis for an ideal delivery system. This paper describes a combinational multiphasic delivery system, where biomolecules are delivered through the fabrication of coaxial electrospinning of different biocompatible polymers. The ratio and specificity of polymers for specific biofunction are optimized and the delivery system is completely characterized with reference to the mechanical property and structural integrity of bromelain (debridement enzyme) and salvianolic acid B (pro-angiogenesis and re-epithelialization). The in vitro release profile illustrated the sustained release of debriding protease and bioactive component in a timely fashion. The fabricated scaffold showed angiogenic potential through in vitro migration of endothelial cells and increased new capillaries from the existing blood vessel in response to an in ovo chicken chorioallantoic membrane assay. In addition, in vivo studies confirm the efficacy of the fabricated scaffold. Our results therefore open up a new avenue for designing a bioactive combinational multiphasic delivery system to enhance wound healing.

Dermatopontin (DPT) is a matricellular protein with cardinal roles in cutaneous wound healing. The protein is also reported to be altered in various anomalies including cancer. The present study is aimed to unravel the role of DPT in angiogenesis which is imperative in many physiological and pathological processes. DPT's capabilities on promoting angiogenesis were assessed using various in vitro and ex vivo systems. The results indicated that DPT enhances cell motility and induces lamellipodia formation in endothelial cells. Additionally, we noticed that DPT stimulates tube formation in endothelial cells when plated on a matrigel substrate. However, it was observed that DPT had no effect on the proliferation of endothelial cells even at higher concentrations and prolonged treatment periods. Additional experiments on CAM and aortic arch assays apparently depicted that DPT promotes neovascularisation and tube sprouting, thus unraveling its prominent role in angiogenesis. Further, PCR analysis revealed that endothelial cells are devoid of DPT expression, but when exogenously supplied, modulates the expression of transforming growth factor β1 and integrin α3β1 which are reported to have crucial roles in endothelial cell behaviour during angiogenesis. In conclusion, DPT possess vital pro-angiogenic properties and thus retains promising therapeutic values in managing chronic wounds and cancer., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Wound healing is a complex cellular process involving various mechanisms making it intricate for designing a scaffold for therapeutic use. This study deals with the designing and development of coaxial electrospun Chitosan-Polycaprolactone nanofiber wound dressings for efficient simultaneous drug delivery. Ferulic acid and resveratrol were chosen for incorporation into core-shell nanofibers for their efficacy in anti-inflammatory and pro-angiogenic activities respectively. Structural and physico-chemical characterization of the scaffold confirmed the encapsulation of both the molecules. The in vitro release studies showed sustained release of both resveratrol and ferulic acid up to 48% and 55% respectively till 120h. Functional characterization of the nanofibrous wound dressing exhibited good in vitro and in vivo biocompatibility. The scaffold treated rats exhibited complete healing in 15days in comparison to the controls that healed in 20days. The study therefore, opens up venues for designing sequential and sustained drug delivery systems in wound therapeutics., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Skin is a very complex organ and hence designing a bioengineered skin model replicating the essential physiological characteristics for replacing the diseased or damaged parts has been a challenging goal for many. Newer technologies for satisfying most of the criteria are being attempted with the copious efforts of biologists, engineers, physiologists, using multitude of features in combination. Amongst them nanotechnology based biomaterials have gained prominence owing to the enhanced pharmacokinetics, bio-distribution profile, extended half-life and reduced side effects. Designing a matrix that can be assimilated into the body during the regeneration and delivering the essential pharmacological agents in a temporal and spatially specific manner is a tremendous goal. This review essentially deals with the various approaches for designing a multidisciplinary translational smart matrix for addressing the various skin related ailments., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A rhodamine-naphthalimide dyad probe, 1, that selectively responds to the addition of trivalent metal ions (Fe(3+) or Al(3+) or Cr(3+)) via ultrafast Förster resonance energy transfer (FRET) from naphthalimide to rhodamine is designed and synthesized. 1 is highly selective to the trivalent metal ions and the presence of other monovalent or divalent metal ions do not affect its detection ability. The probe is highly sensitive and it can respond to the presence of trivalent metal ions even at sub-micromolar levels. 1 is stable over a broad range of pH, non-toxic under experimental conditions and suitable to the fluorescence bio-imaging of live cells exposed to trivalent metal ions. The trivalent metal ion induced ultrafast energy transfer kinetics of 1 is explored using time resolved fluorescence experiments., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The current study aims at understanding the influence of curcumin caged silver nanoparticle (CCSNP) on stability of collagen. The results indicated that curcumin caged silver nanoparticles efficiently stabilize collagen, indicated by enhanced tensile strength, fibril formation and viscosity. The tensile strength of curcumin caged silver nanoparticle cross-linked collagen and elongation at break was also found to be higher than glutaraldehyde cross-linked collagen. The physicochemical characteristics of curcumin caged nanoparticle cross-linked collagen exhibited enhanced strength. The thermal properties were also good with both thermal degradation temperature and hydrothermal stability higher than native collagen. CD analysis showed no structural disparity in spite of superior physicochemical properties suggesting the significance of curcumin caged nanoparticle mediated cross-linking. The additional enhancement in the stabilization of collagen could be attributed to multiple sites for interaction with collagen molecule provided by curcumin caged silver nanoparticles. The results of cell proliferation and anti-microbial activity assays indicated that curcumin caged silver nanoparticles promoted cell proliferation and inhibited microbial growth making it an excellent biomaterial for wound dressing application. The study opens scope for nano-biotechnological strategies for the development of alternate non-toxic cross-linking agents facilitating multiple site interaction thereby improving therapeutic values to the collagen for biomedical application., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The present work describes the development of a novel wound dressing material based on nano-biotechnological intervention by caging plumbagin on silver nanoparticle (PCSN) as a multi-site cross-linking agent of collagen scaffolds with potent anti-microbial and wound healing activity. Cross-linking of collagen with PCSN enhanced the physical, thermal, and mechanical properties along with the kinetics of micro structural fibril assembly of the collagen molecule. FTIR and CD analysis revealed that cross-linking of collagen using PCSN did not induce any structural changes in the collagen molecule. Further, cross-linking of collagen with PCSN resulted in uniform alignment of collagen fibrils to form orderly aligned porous structured scaffolds with potent anti-bacterial activity that in turn enhanced its ability to promote cell proliferation and wound healing. The cross-linking ability, and biochemical and therapeutic properties of plumbagin caged silver nanoparticles were attributed to the cumulative effect of plumbagin and silver nanoparticles because individual molecules had minimal effect on these parameters.

In this study, zein nanofibers based siRNA delivery system has been attempted for the first time. Here, the amphiphilic property of zein and the size advantage of nanofibers have been brought together in developing an ideal delivery system for siRNA. The morphological analysis of the GAPDH-siRNA loaded zein nanofibers revealed the proper encapsulation of the siRNA in the polymeric matrix. The loading efficiency of this delivery system was found to be 58.57±2.4% (w/w). The agarose gel analysis revealed that the zein nanofibers preserved the integrity of siRNA for a longer period even at the room temperature. The in vitro release studies not only depicted the sustaining potential of the zein nanofibers but also ensured the release of sufficient quantity of siRNA required to induce the gene silencing effect. The amphiphilic property of zein supported the cell attachment and thereby facilitated the transfection of siRNA into the cells. qRT-PCR analysis confirmed the potential of the developed system in inducing the desired gene silencing effect. Thus, electrospun zein nanofibers have been successfully employed for the delivery of siRNA which has a great therapeutic potential.

A naphthalimide based fluorescent probe '1' that operates based on photoinduced electron transfer phenomenon is synthesized and its chemosensory application is explored. Among various metal ions, 1 selectively detects Fe(3+) with a detection limit of 3.0 × 10(-8) M. 1 is stable at physiological pH, nontoxic under experimental conditions and suitable for the detection of Fe(3+) ions present in aqueous samples and live cells.

Re-epithelialization is a key event in wound healing and any impairment in that process is associated with various pathological conditions. Epidermal keratinocyte migration and proliferation during re-epithelialization is largely regulated by the cytokines and growth factors from the provisional matrix and dermis. Extracellular matrix consists of numerous growth factors which mediate cell migration via cell membrane receptors. Dermatopontin (DPT), a non-collagenous matrix protein highly expressed in dermis is known for its striking ability to promote cell adhesion. DPT also enhances the biological activity of transforming growth factor beta 1 which plays a central role in the process of wound healing. This study was designed to envisage the role of DPT in keratinocyte migration and proliferation along with its mRNA and protein expression pattern in epidermis. The results showed that DPT promotes keratinocyte migration in a dose dependant fashion but fail to induce proliferation. Further, PCR and immunodetection studies revealed that the mRNA and protein expression of DPT is considerably negligible in the epidermis in contrast to the dermis. To conclude, DPT has a profound role in wound healing specifically during re-epithelialization by promoting keratinocyte migration via paracrine action from the underlying dermis.

Chronic cutaneous wound (CCW) is a major health care burden wherein the healing process is slow or rather static resulting in anatomical and functional restriction of the damaged tissue. Dysregulated expression and degradation of matrix proteins, growth factors and cytokines contribute to the disrupted and uncoordinated healing process of CCW. Therefore, therapeutic approaches for effective management of CCW should be focused towards identifying and manipulating the molecular defects, such as reduced bioavailability of the pro-healing molecules and elevated activity of proteases. This study essentially deals with assessing the expression and integrity of an extracellular matrix protein, Dermatopontin (DPT), in CCW using real-time quantitative reverse transcriptase PCR and immunological techniques. The results indicate that, despite DPT's high mRNA expression, the protein levels are markedly reduced in both CCW tissue and its exudate. To elucidate the cause for this contradiction in mRNA and protein levels, the stability of DPT is analyzed in the presence of wound exudates and various proteases that are naturally elevated in CCW. DPT was observed to be degraded at higher rates when incubated with certain recombinant proteases or chronic wound exudate. In conclusion, the susceptibility of DPT protein to specific proteases present at high levels in the wound milieu resulted in the degradation of DPT, thus leading to impaired healing response in CCW.

In this study, we have evaluated the interactions of zein microspheres with different class of drugs (hydrophobic, hydrophilic, and amphiphilic) using in vitro and in silico analysis. Zein microspheres loaded with aceclofenac, metformin, and promethazine has been developed by solvent evaporation technique and analyzed for its compatibility. The physical characterization depicted the proper encapsulation of hydrophobic drug in the microspheres. The in vitro release study revealed the sustaining ability of the microspheres in the following order: hydrophobic > hydrophilic > amphiphilic. In silico analysis also confirmed the better binding affinity and greater interactions of hydrophobic drug with zein. The above results revealed that zein is more suitable for hydrophobic drugs in the development of sustained drug delivery systems using solvent evaporation technique. The study therefore envisages a scope for identifying the most suitable polymer for a sustained drug delivery system in accordance with the nature of the drug.

Centrifugal spinning (C-Spin) is an emerging technology which uses centrifugal force to produce ultrafine fibers. Being a voltage free technique it can overcome the limitations of electrospinning. Owing to the unique characteristic features such as high surface area to volume ratio, porosity, mechanical strength and fiber alignment, centrifugal spun (C-spun) fibrous mat has a wide range of scope in various biomedical applications. Higher degree of fiber alignment can be effortlessly achieved by the C-Spin process. In order to prove the versatility of C-Spin system with respect to fiber alignment, Polycaprolactone (PCL) and gelatin were spun taking them as model polymers. The morphological analysis revealed that highly aligned ultrafine fibers with smooth surface are achieved by C-Spinning. Hydrophilicity, porosity and mechanical property results confirm that the C-spun mat is more suitable for tissue engineering applications. In vitro and in vivo experiments proved that the scaffolds are biocompatible and can be efficiently used as a wound dressing material., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Furfural (2-furancarboxaldehyde), a product derived from plant pentosans, has been investigated for its interaction with collagen. Introduction of furfural during fibril formation enhanced the thermal and mechanical stability of collagen. Collagen films treated with furfural exhibited higher denaturation temperature (Td) (p<0.04) and showed a 3-fold increase in Young's modulus (p<0.04) at higher concentration. Furfural and furfural treated collagen films did not have any cytotoxic effect. Rheological characterization showed an increase in shear stress and shear viscosity with increasing shear rate for treated collagen. Circular dichroism (CD) studies indicated that the furfural did not have any impact on triple helical structure of collagen. Scanning electron microscopy (SEM) of furfural treated collagen exhibited small sized porous structure in comparison with untreated collagen. Thus this study provides an alternate ecologically safe crosslinking agent for improving the stability of collagen for biomedical and industrial applications., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Incorporation of the triazolyl moiety modulates the basicity and effective size of the chelating ring, changes the stoichiometry in complex formation and thereby imparts Cu(2+) ion selectivity.

Two new rhodamine–indole conjugates 1 and 2 were synthesized for studying their ability to probe specific metal ions at physiological pH in the presence of other competing metal ions. In non-aqueous medium, probe 1 predominantly binds Cu(2+) ions with considerable interference from Fe(3+) and Ni(2+) ions. However, in aqueous medium, 1 exhibits a higher degree of selectivity for Cu(2+) ions with little interference from Fe(3+) ions, and no interference from Ni(2+) ions. The probe 2, obtained by tethering a triazole moiety with probe 1, selectively binds Cu(2+) ions in aqueous medium even in the presence of other metal ions including Fe(3+) ions. The sensitivity of probe 2 to pH variation and interaction with various amino acids were also investigated. The excellent stability of 2 in physiological pH conditions, non-toxicity, non-interference of amino acids in the detection process, and the remarkable selectivity for Cu(2+) ions in aqueous medium allowed the use of 2 in the imaging of live fibroblast cells treated with Cu(2+).

Electrospun composite zein/eudragit nanofibers were developed with an aim to deliver two different classes of drugs simultaneously that would restrict/compensate the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs). Co-administration of proton pump inhibitors is beneficial for patients consuming NSAIDs for treating chronic ailments like arthritis. In this study, aceclofenac/pantoprazole loaded zein/eudragit S 100 nanofibers were developed using a single nozzle electrospinning process. The morphological analysis revealed the uniform and smooth surface of the drug loaded nanofibers. The physico-thermal characterization of nanofibers depicted the molecular integration of the drugs with the polymers and also confirmed that the drugs were evenly distributed in the nanofibers in an amorphous state. In vitro release studies ensure the efficiency of the developed fibers in sustaining the release of both the drugs up to 8h. In vivo animal experiments further confirmed that the co-administration of pantoprazole along with aceclofenac reduced the gastro-intestinal toxicity induced by NSAIDs. The histological evaluation revealed the preserved mucosal architecture of rat gastric tissue treated with drug loaded composite nanofibers. Thus, dual drug delivery system comprising polymers with different release characteristics has been successfully developed and further, oral delivery of aceclofenac with reduced side effects was achieved., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastric injury on long-term usage. This study aims at reducing the side effect of NSAIDs by encapsulating in zein, an acid-resistant biopolymer. Aceclofenac-loaded zein microspheres were prepared by emulsification and solvent evaporation method. The stability of zein microspheres at gastric pH retarded the release of the entrapped drug and hence reduces the possibility of gastric injury. However, the in vitro release of aceclofenac was sustained up to 72 h at intestinal pH. Thus, zein microspheres pave the way for the development of safe and sustained delivery system for NSAIDs thereby achieving the desired therapeutic potential with reduced side effects for chronic inflammatory disorders.