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Abstract Background Specific properties of amphiphilic copolymeric micelles like small size, stability, biodegradability and prolonged biodistribution have projected them as promising vectors for drug delivery. To evaluate the potential of δ-valerolactone based micelles as carriers for drug delivery, a novel triblock amphiphilic copolymer poly(δ-valerolactone)/poly(ethylene glycol)/poly(δ-valerolactone) (VEV) was synthesized and characterized using IR, NMR, GPC, DTA and TGA. To evaluate VEV as a carrier for drug delivery, doxorubicin (DOX) entrapped VEV micelles (VEVDMs) were prepared and analyzed for in vitro antitumor activity. Results VEV copolymer was successfully synthesized by ring opening polymerization and the stable core shell structure of VEV micelles with a low critical micelle concentration was confirmed by proton NMR and fluorescence based method. Doxorubicin entrapped micelles (VEVDMs) prepared using a modified single emulsion method were obtained with a mean diameter of 90 nm and high encapsulation efficiency showing a pH dependent sustained doxorubicin release. Biological evaluation in breast adenocarcinoma (MCF7) and glioblastoma (U87MG) cells by flow cytometry showed 2-3 folds increase in cellular uptake of VEVDMs than free DOX. Block copolymer micelles without DOX were non cytotoxic in both the cell lines. As evaluated by the IC50 values VEVDMs induced 77.8, 71.2, 81.2% more cytotoxicity in MCF7 cells and 40.8, 72.6, 76% more cytotoxicity in U87MG cells than pristine DOX after 24, 48, 72 h treatment, respectively. Moreover, VEVDMs induced enhanced apoptosis than free DOX as indicated by higher shift in Annexin V-FITC fluorescence and better intensity of cleaved PARP. Even though, further studies are required to prove the efficacy of this formulation in vivo the comparable G2/M phase arrest induced by VEVDMs at half the concentration of free DOX confirmed the better antitumor efficacy of VEVDMs in vitro. Conclusions Our studies clearly indicate that VEVDMs possess great therapeutic potential for long-term tumor suppression. Furthermore, our results launch VEV as a promising nanocarrier for an effective controlled drug delivery in cancer chemotherapy.

Aluminium-based single films were pulled out of a melt using circular wire frames and characterised with respect to their stability under varied conditions. Pure Al, AlSi9 and AlSi9Mg0.6 alloys as well as particle reinforced composites based on the same alloys but adding different amounts of stabilising SiC or TiB2 particles were prepared. The velocity at which films were drawn was varied to investigate their solidification as well as their oxidation behaviour. In order to study the influence of the oxygen content of the foaming atmosphere a chamber was manufactured that allows for pulling single films under defined conditions. It was found that films without Mg were less stable than Mg-containing ones and even the addition of particles to such Mg-free alloys results in no improvement. In contrast, films made of AlSi9Mg0.6 were more stable and required only a small amount of oxygen (> 200 ppm O2), but in general some oxygen has always to be present to obtain a stable film. It was found that the more particles are contained in the composite and the slower the film gets pulled, the lower the required oxygen content is. [ABSTRACT FROM AUTHOR]

Aluminum alloys made from machining chips that have been heat treated and re-melted, have been successfully foamed (after the addition of TiH2) using processes analogous to both the 'Alporas' and 'Formgrip' methods. The high oxygen contents associated with the swarf (0.11 wt% for the as-received material, increasing to >0.5 wt% after conditioning) results in large fractions of both clustered and dispersed oxide films in the melt. It is these films that enhance the 'foamability' of this material. Through additional alloying with Mg and holding in the liquid state to allow reaction to take place, fragmentation and wetting of the oxides occurs and foams with low densities (<0.3 g cm−3), good pore structures, and good stability were obtained. The use of scrap material, without costly or embrittling additives, offers a low cost route to the manufacture of high quality foams. [ABSTRACT FROM AUTHOR]

The poor corneal residence time of pilocarpine, an alkaloid extracted from the leaves of the Jaborandi plant, limits its ocular application. The aim of this study was to develop, characterize, and evaluate the potential of pilocarpine entrapped by poly( DL-lactic- co-glycolic acid) (PLGA) nanoparticle carriers for ocular drug delivery. Pilocarpine-loaded nanoparticles were prepared with a double-emulsion (water in oil in water) method and characterized with transmission electron microscopy and X-ray diffraction analysis. The nanoparticles exhibited an average size of 82.7 nm with an encapsulation efficiency of 57%. Stability studies showed the absence of agglomeration and constancy in the amount of drug entrapped; this indicated the solidity of these particles for long-term use. The in vitro release studies conducted in simulated tear fluid showed the sustained release of pilocarpine. In vivo evaluation of the nanoparticles was done in a rabbit model with a miosis assay and compared to an equal dose of commercially available eye drops of pilocarpine (Pilocar drops). The in vivo miosis studies showed that the duration of miotic response increased by 40% for the nanoparticles and produced an almost 68% increase in total miotic response when compared to the eye drops. In conclusion, this study clearly demonstrated the potential of pilocarpine-loaded PLGA nanoparticles for multiplying the therapeutic effect of ophthalmic drug delivery with enhanced bioavailability and pharmacological response. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

The settling behaviour of heterogeneous nucleating particles such as TiAl3, TiB2, AlB2 and TiC in liquid Al has been studied through vertical sectioning experiments. The experimental results obtained were correlated with the settling rate of the particles calculated using the Stokes' law. The TiB2 and TiC particles show larger settling tendency among all particles studied. The overall settling behaviour of the particles is largely influenced by their size distribution in their respective master alloys, their agglomeration and dissolution behaviour in the liquid Al. [ABSTRACT FROM AUTHOR]

The effect of TiAl3 particle size and distribution on their settling and dissolution behaviour in molten aluminium during grain refinement has been studied. For this purpose Al–5Ti master alloys containing blocky TiAl3 particles of different size and distribution are synthesised at reaction temperatures 750, 800 and 850 °C for 60 min and used for grain refinement. The extent of fading and the recovery due to stirring is calculated from the measured grain size and used to judge the dissolution and settling behaviour of TiAl3 in molten Al, which is greatly attributed to its size and distribution in Al–5Ti master alloy. Fine TiAl3 particle dissolve faster in the melt and cause fading. Larger size TiAl3 particles exist for longer time in molten Al and act as a nucleating site even when added in hypoperitectic concentration (0.05 wt% Ti). [ABSTRACT FROM AUTHOR]

An investigation into the effect of ternary alloying element additions such as copper, magnesium, manganese, zinc, and nickel on pore formation in cast Al-12.6-wt pct Si eutectic alloy by employing a novel pore characterization technique is reported here. In this approach, the low-pressure testing method was combined with the metal foam manufacturing technique of intentionally adding TiH2, which enhances hydrogen pore formation and offers a method to distinguish the effect of individual alloying elements on hydrogen porosity formation. [ABSTRACT FROM AUTHOR]

Severe burns pose significant threats to patient well-being, characterized by pain, inflammation, bacterial infection, and extended recovery periods. While exosome-loaded hydrogels have demonstrated considerable promise in wound healing, current formulations often fall short of achieving optimal therapeutic efficacy for burn wounds due to challenges related to their adaptability to wound shape and limited anti-bacterial capabilities. In this study a novel exosome laden sprayable thermosensitive polysaccharide-based hydrogel (ADA-aPF127@LL18/Exo) comprising alginate dialdehyde (ADA) and aminated Pluronic F127 (aPF127) was fabricated via Schiff base reaction. ADA-aPF127@LL18/Exo exhibited sustained release of exosome and enhanced antibacterial efficacy. Furthermore, the biological assessments displayed excellent biocompatibility and enhanced in vitro cell proliferation and migration. In a deep partial thickness burn model, ADA-aPF127@LL18/Exo significantly augmented wound healing processes by accelerating epithelialization, promoting granulation tissue formation and collagen deposition, inducing hair follicle regeneration, effectively mitigating inflammatory responses, and facilitating enhanced neovascularization. In conclusion, ADA-aPF127@LL18/Exo represents a highly promising therapeutic dressing for the treatment of deep burns, exhibiting multifaceted properties conducive to efficient wound management., Competing Interests: Declaration of competing interest We disclose that this manuscript has not been published previously and is not under consideration of any other journal. All authors agree with the submission of this manuscript to International Journal of Biological Macromolecules. We affirm that all in vivo work was approved by IACUC and met all institutional, state, and national ethical standards. We declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We have investigated the wound healing efficiency of calcium alginate wafer embedded with growth factor entrapped PLGA nanoparticle. Herein, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) entrapped PLGA nanoparticles were synthesized and embedded in a sodium alginate gel by freeze-drying technique. The synthesized dressing exhibited a high degree of swelling and appropriate porosity. The scaffold was characterized by Scanning Electron Microscopy (SEM) showing a highly porous morphology. Also, incorporation of growth factor loaded nanoparticles in a wafer-based delivery system resulted in localized growth factor delivery at the site of the wound in a sustained manner. The biocompatibility of the scaffold was evaluated by MTT assay, which showed a higher cell proliferation in the proposed scaffold as compared to the control. In vivo wound healing efficiency of the scaffold was evaluated using a full thickness murine wound model, which showed improved re-epithelialization, collagen deposition, and angiogenesis. These results suggest the use of the scaffold as a promising wound dressing material., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The brain, protected by the cranium externally and the blood-brain barrier (BBB) internally, poses challenges in chemotherapy of aggressive brain tumors. Maximal tumor resection followed by radiation and chemotherapy is the standard treatment protocol; however, a substantial number of patients suffer from recurrence. Systemic circulation of drugs causes myelodysplasia and other side effects. To address these caveats, we report facile synthesis of a polyester-based supramolecular hydrogel as a brain biocompatible implant for in situ delivery of hydrophobic drugs., Methods: Polycaprolactone-diol (PCL) was linked to polyethyleneglycol-diacid (PEG) via an ester bond. In silico modeling indicated micelle-based aggregation of PCL-PEG co-polymer to form a supramolecular hydrogel. Brain biocompatibility was checked in Sprague Dawley rat brain cortex with MRI, motor function test, and histology. Model hydrophobic drugs carmustine and curcumin entrapment propelled glioma cells into apoptosis-based death evaluated by in vitro cytotoxicity assays and Western blot. In vivo post-surgical xenograft glioma model was developed in NOD-SCID mice and evaluated for efficacy to restrict aggressive regrowth of tumors., Results: 20% (w/v) PCL-PEG forms a soft hydrogel that can cover the uneven and large surface area of a tumor resection cavity and maintain brain density. The PCL-PEG hydrogel was biocompatible, and well-tolerated upon implantation in rat brain cortex, for a study period of 12 weeks. We report for the first time the combination of carmustine and curcumin entrapped as model hydrophobic drugs, increasing their bioavailability and yielding synergistic apoptotic effect on glioma cells. Further in vivo study indicated PCL-PEG hydrogel with a dual cargo of carmustine and curcumin restricted aggressive regrowth post-resection significantly compared with control and animals with intravenous drug treatment., Conclusion: PCL-PEG soft gel-based implant is malleable compared with rigid wafers used as implants, thus providing larger surface area contact. This stable, biocompatible, supramolecular gel without external crosslinking can find wide applications by interchanging formulation of various hydrophobic drugs to ensure and increase site-specific delivery, avoiding systemic circulation., Competing Interests: The authors declare no conflicts of interest in this work., (© 2022 Wanjale et al.)

Hard to heal wounds such as diabetic wounds is one of the major problems in the healthcare sector. Delayed healing and shortfall of functional restoration at the wound site require upgraded wound management aids. In this study, we report that a nanofibrous mat enriched with bioactive peptides laden nano and microparticles achieve the requirements as an effective diabetic wound dressing. By means of electrospinning method, we fabricated Poly (lactic- co -glycolic acid)/Collagen nano-scale mat and surface functionalised with wound healing peptides, laden Chitosan nano and micro-sized particles, creating an Extracellular Matrix (ECM) -like structure with biomimetic features. The developed dressing displayed good cytocompatibility with Keratinocyte and fibroblast cells and enhanced their in-vitro cell proliferation and migration. Experiments in the streptozotocin-induced diabetic mice model showed that bioactive peptides released from Chitosan particles shorten the inflammatory stage and promote neovascularisation. The supporting nanoscale matrix promotes increased collagen deposition in the wound beds, thereby hastening the complete healing process by substantial tissue re-generation and functional restoration. The results evince that the nano/microparticles enriched nano-scale mat show potential as an effective wound repair dressing for diabetic wounds., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd.)

Background: Treatment of wounds with the help of nanoparticles (NPs) is more effective and superior in comparison to traditional wound healing methods as it protects and sustains active drug release at the wound site thus enhancing the safety of the drug and reducing the possibility of side effects. The advantages of this method are the possibility of allowing a reduction in administered dose, limiting toxicity levels to the minimum, and increasing safety of topical delivery of the drug., Materials and Methods: We report the synthesis of a novel poly (lactic-co-glycolic acid) (PLGA) NP-based multicargo delivery system for growth factors and antimicrobial peptide. Growth factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were entrapped in PLGA NPs by solvent diffusion method and an antimicrobial peptide (K4) was conjugated to the NP by carbodiimide chemistry. The developed multiple cargo delivery systems with growth factors (VEGF and bFGF) and an antimicrobial peptide (K4) were investigated and optimized for potential wound healing., Results: The system showed a sustained release of growth factors and was evaluated for cytotoxicity by MTT and live/dead assay, which revealed that the bioactivity of the growth factor-entrapped NPs was higher than that of free growth factors, and it also induced enhanced cell proliferation in vitro., Conclusion: The development of a system for the codelivery of growth factors (VEGF and bFGF) and an antimicrobial peptide (K4) was investigated for potential wound healing application. The entrapment of growth factors with very high efficiency is an advantage in this method along with its sustained release from the nanoparticulate system, which will enhance the angiogenesis. Our system also displayed broad-spectrum antimicrobial activity against both gram-positive and gram-negative bacteria., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Dry powder inhalers (DPI) attracted the attention of pharmaceutical field due to its enlarging market share in inhalable formulations. These formulations also pose patient compliance and good shelf life. Earlier DPI formulations were intended for local effect in lung (asthma and chronic obstructive pulmonary diseases), whereas 21(st) century witnessed formulations intended for systemic effect too. A better understanding of physiology of lung and fluidics of air flow helped in targeting alveoli using DPI technology. Modern characterization tools also accelerated the research pace. In addition to the synthetic molecules, DPI also was proved to be a better system for delivering biological molecules including vaccines. This review includes the mechanisms of drug deposition, advancements in the fields of DPI devices, various characterization tools and particle engineering. In this review we have related the chronological advancement of inhalational technology starting from 1788 AD to the present.

We now report the synthesis of a random copolymer of poly-lactic-co-glycolic acid (PLGA) grafted branched polyethylenimine (BPEI) and the use of it as a multi drug delivery system (DDS). The methotrexate (MTX) was conjugated to BPEI through DCC/NHS chemistry. The copolymer-drug conjugate (PBP-MTX) was characterised by FT-IR and (1)H NMR spectroscopy. The PBP-MTX was converted into nanomicelles with entrapped 5-fluorouracil (5-FU) through nanoprecipitation technique. The size, shape, morphology and surface charge of the nanomicelles were confirmed using different techniques. The thermal behaviour and distribution of both conjugated and entrapped drug through the polymeric matrix were assessed by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis (PXRD). In vitro drug release pattern of the nanomicelles was examined to ascertain the release pattern of two drugs namely 5-FU and MTX. The cellular uptake studies demonstrated higher uptake of the nanomicelles in colon cancer cell line HCT 116. Further the cytotoxicity evaluation of nanomicelles illustrated promising action which confirms the use of the system as a potential DDS to colon cancer., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Excipients having self-assembling properties are less explored in the field of dry powder inhalation (DPI) technology. An amphiphilic lipopolymer system was developed using stearic acid (SA) and branched polyethyleneimine (BPEI) (1800 Dalton), at different proportions by covalent conjugation. A molecular dynamic (MD) simulation tool was employed for predicting the carrier behavior in a polar in vivo condition. The structural characterization was carried out using nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared (FTIR) spectroscopy. The physical nature of the lipopolymer was analyzed by differential scanning calorimetry. Determination of zeta potential and diameter of the micelles showed existence of cationic particles in the nano size range when a lower number of primary amino groups of BPEI was grafted with SA. The rifampicin (RIF)-loaded lipopolymer was also formulated further into spray-dried microparticles. Powder X-ray diffraction (PXRD) studies revealed that the RIF API (active pharmaceutical ingredient) exists as molecular dispersion in spray-dried microparticles. Topological analysis of the spray-dried nanomicelle was carried out using scanning electron microscopy (SEM). A large population of the drug-carrying particles were found to be under the inhalable size range (fine particle fraction 67.88% ± 3%). In vitro drug release kinetics from spray-dried nanomicelles were carried out at lung fluid pH.

Curcumin, a yellow pigment present in turmeric, possess potential anti-proliferative and anti-inflammatory activities but poor aqueous solubility limits its applications. In this study we report a novel comparative study of the formulation and characterization of curcumin nanoparticles (nanocurcumin) using two poly (lactide-co-glycolide) (PLGA) combinations, 50:50 and 75:25 having different lactide to glycolide ratios. Nanocurcumin 50:50 showed smaller size with higher encapsulation efficiency. Thermal evaluation suggested the presence of curcumin in molecular dispersion form which supported its sustained release up to a week where nanocurcumin 50:50 showed faster release. Cellular uptake studies in human epithelial cervical cancer cells (HeLa) exhibited enhanced intracellular fluorescence with nanocurcumin when compared to free curcumin, when both given in purely aqueous media. Antiproliferative studies using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Annexin V/propidium iodide staining, poly (ADP-ribose) polymerase (PARP) cleavage and downregulation of clonogenic potential of HeLa cells proved the better antitumor activity of nanocurcumin 50:50 administered in aqueous media. Superior efficacy of nanocurcumin 50:50 in comparison to free curcumin was further demonstrated by electrophoretic mobility shift assay and immunocytochemical analysis. In conclusion, the enhanced aqueous solubility and higher anticancer efficacy of nanocurcumin administered in aqueous media clearly demonstrates its potential against cancer chemotherapy, with dependence on the combination of PLGA., (Copyright © 2012. Published by Elsevier B.V.)

Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy.

Novel cross-linked polymeric support by the copolymerization of styrene and 3-(acryloyloxy)-2-hydroxypropyl methacrylate with Tri(propyleneglycol) diacryalte (SAT) for solid-phase peptide synthesis is presented here. The synthesis of SAT is based on the cross-linking of 3-(acryloyloxy)-2-hydroxypropyl methacrylate with styrene by free-radical suspension polymerization, consisting of an ester and a secondary hydroxyl group. An additional cross-linker tri(propyleneglycol) diacryalte provides a hydrophilic environment throughout the resin, which will enhance the physicochemical properties of the resin toward organic synthesis. The resins were synthesized in various cross-linking densities to check the swelling property, mechanical stability, and functional loading capacity. The resin was characterized by the IR, (13)C NMR, and SEM techniques. The extent of swelling properties of the polymer of different cross-linking densities were studied and compared with Merrifield resin and TentaGel. To demonstrate the efficiency of SAT support was proved by synthesizing the challenging peptide sequence of acyl carrier protein (ACP) and compared with commercially available Merrifield resin. It was further tested by synthesizing endothelial receptor antagonist peptides using SAT resin and compared with commercially available TentaGel resin. The standard Fmoc strategy was adopted for peptide synthesis and was characterized by MALDI-TOF MS and analyzed the purity of peptides by HPLC.

A high swelling resin, CLPSER has been developed and utilized for the solid phase synthesis of Pardaxin, which is an 18-residue peptide. The resin was characterized by gel phase (13)C NMR, IR and SEM. The utility of the new polymer support in polypeptide synthesis was further established by the comparative synthesis of pardaxin with commercially available Merrifield resin. The MALDI TOF MS, amino acid analysis and the HPLC revealed the superior quality of CLPSER.