Polymeric Nanoformulation of Zoledronic Acid Rescues Osteoblasts from the Harmful Effect of its Native Form: An In Vitro Investigation of Cytotoxic Potential on Osteoblasts and Osteosarcoma Cells.

Osteosarcoma (OS) is a malignant tumor, fatal for pediatric patients who do not respond to chemotherapy, alternative therapies and drugs can provide better outcomes. Zoledronic acid (Zol) belonging to the class of bisphosphonates (BPs) has a direct antitumor ability to prevent Ras GTPases modification and stimulate apoptosis. Despite advances in maintaining balance in skeletal events and direct anticancer properties, Zol causes cytotoxicity to normal healthy pre-osteoblast cells, hampering mineralization and differentiation. The study reports the preparation and evaluation of a nanoformulation that can diminish the existing drawbacks of native Zol. The cytotoxic effect is evaluated on bone cancer cells and healthy bone cells with three different cell lines namely, K7M2 (mouse OS cell line), SaOS2 (human OS cell line), and MC3T3E1 (healthy cell counterpart). It is observed that Zol nanoformulation is uptaken more (95%) in K7M2 whereas in MC3T3E1, the percent population internalizing nanoparticles (NPs) is 45%. Zol has a sustained release of 15% after 96 h from the NP which leads to a rescuing effect on the normal pre-osteoblast cells. In conclusion, it can be stated that Zol nanoformulation can be used as a good platform for a sustained release system with minimum side effects to normal bone cells.

The role of polyplexes in developing a green sustainable approach in agriculture.

Rise in global population has increased the food demands and thus the competition among farmers to produce more and more. In the race to obtain higher productivity, farmers have resorted to injudicious farming practices that include the reckless use of nitrogenous fertilizers and intensive cropping on farmlands. Such practices have paved the path for large scale infestations of crops and plants by pests thus affecting the plant productivity and crop vigour. There are several traditional techniques to control pest infestations in plants such as the use of chemical or bio-pesticides, and integrated pest management practices which face several drawbacks. Delivery of gene/nucleic acid in plants through genetic engineering approaches is a more sustainable and effective method of protection against pests. The technology of RNA interference (RNAi) provides a sustainable solution to counter pest control problems faced by other traditional techniques. The RNAi technique involves delivery of dsDNA/dsRNA or other forms of nucleic acids into target organisms thereby bringing about gene silencing. However, RNAi is also limited to its use because of their susceptibility to degradation wherein the use of cationic polymers can provide a tangible solution. Cationic polymers form stable complexes with the nucleic acids known as "polyplexes", which may be attributed to their high positive charge densities thus protecting the exogenous nucleic acids from extracellular degradation. The current paper focuses on the utility of nucleic acids as a sustainable tool for pest control in crops and the use of cationic polymers for the efficient delivery of nucleic acids in pests thus protecting the plant from infestations.

A Review on Re-Packaging of Bisphosphonates Using Biomaterials.

The need for bone repair and insight into new regeneration therapies as well as improvement of existing regeneration routes is constantly increasing as a direct consequence of the rise in the number of trauma victims, musculoskeletal disorders, and increased life expectancy. Bisphosphonates (BPs) have emerged as a class of drugs with proven efficacy against many bone disorders. The most recent ability of this class of drugs is being explored in its anti-cancer ability. However, despite the pharmacological success, there are certain shortcomings that have circumvented this class of the drug. The mediation of biomaterials in delivering bisphosphonates has greatly helped in overcoming some of these shortcomings. This article is focused on reviewing the benefits the bisphosphonates have provided upon getting delivered via the use of biomaterials. Furthermore, the role of bisphosphonates as a potent anticancer agent is also accounted. It is witnessed that employing engineering tools in combination with therapeutics has the potential to provide solutions to bone loss from degenerative, surgical, or traumatic processes, and also aid in accelerating the healing of large bone fractures and problematic non-union fractures. The role of nanotechnology in enhancing the efficacy of the bisphosphonates is also reviewed and innovative approaches are identified.

Cell membrane coated nanocarriers - an efficient biomimetic platform for targeted therapy.

Targeted therapy approaches have become the core of modern translational science and as an intriguing field, it is the solution of the conventional drug delivery problems that were once unanswered. Traditional methods of delivering drugs and therapeutics faced issues of solubility, sustained release, not enough amount getting through the diseased site, for e.g a tumor. Various formulations of liposomes, polymers, dendrimers, etc have succeeded and made their way for clinical trials trying to enhance the pharmacokinetic and biodistribution of the drug. Many stealth coatings that include hydrophilic polymers (PEG, chitosan, polyacrylamides, etc) can act as a covering around the nanoparticle that can shield the surface from aggregation, opsonization and evade immune system, thus considered in Generally Recognized as Safe (GRAS) category. Several other polymers such as poly-2-oxazoline, polyethylene oxide, PEG-based surfactant (polysorbate-80), and zwitterionic phospholipids have also been tested for their antifouling properties. However, the polymer coating approach requires labor-intensive procedures and conjugation chemistries that often fail in mice model. Besides, due to immunogenicity and allergic reactions evoked by the PEG-coated nanoparticles, there was an urge to find biomimicking materials that can prove better as shielding agents which paved the way for cell membrane coated nanoparticles (CMCNPs) to come into the limelight. CMCNPs consist of a nanoparticle inner core covered by cell membrane that can be implicated in targeted drug delivery approaches, photothermal therapy, diagnosis or imaging making it a powerful theranostic tool. In this review, mode of preparation of CMCNPs, different sources of cell membranes (RBCs, WBCs, platelets, cancer cells, stem cells with some other unconventional sources) and nanoparticle cores that are employed have been thoroughly emphasized. In addition to this, advancements and limitations with respect to this newly emerging field have been focussed.

Increased RNAi Efficacy in Spodoptera exigua via the Formulation of dsRNA With Guanylated Polymers.

Lepidoptera comprise some of the most devastating herbivorous pest insects worldwide. One of the most promising novel pest control strategies is exploiting the RNA interference (RNAi) mechanism to target essential genes for knockdown and incite toxic effects in the target species without harming other organisms in the ecosystem. However, many insects are refractory to oral RNAi, often due to rapid degradation of ingested dsRNA in their digestive system. This is the case for many lepidopteran insects, including the beet armyworm Spodoptera exigua, which is characterized by a very alkaline gut environment (pH > 9.0) and a strong intestinal nucleolytic activity. In this research, guanidine-containing polymers were developed to protect dsRNA against nucleolytic degradation, specifically in high pH environments. First, their ability to protect dsRNA against nucleolytic degradation in gut juice of the beet armyworm S. exigua was investigated ex vivo. Polymers with high guanidine content provided a strong protection against nucleolytic degradation at pH 11, protecting the dsRNA for up to 30 h. Next, cellular uptake of the dsRNA and the polyplexes in lepidopteran CF203 midgut cells was investigated by confocal microscopy, showing that the polymer also enhanced cellular uptake of the dsRNA. Finally, in vivo feeding RNAi bioassays demonstrated that using these guanidine-containing polymer nanoparticles led to an increased RNAi efficiency in S. exigua. Targeting the essential gene chitin synthase B, we observed that the mortality increased to 53% in the polymer-protected dsRNA treatment compared to only 16% with the naked dsRNA and found that polymer-protected dsRNA completely halted the development of the caterpillars. These results show that using guanylated polymers as a formulation strategy can prevent degradation of dsRNA in the alkaline and strongly nucleolytic gut of lepidopteran insects. Furthermore, the polymer also enhances cellular uptake in lepidopteran midgut cells. This new delivery strategy could be of great use in further fundamental research in lepidopterans, using RNAi as a research tool, and could lead to future applications for RNAi-based pest control of lepidopteran insects.

Oil-in-water emulsion impregnated electrospun poly(ethylene terephthalate) fiber mat as a novel tool for optical fiber cleaning.

HYPOTHESIS: The complete removal of remaining polymer debris after stripping of optical fiber cables is essential for high precision connection between two fibers. It can be anticipated that electrospun porous membranes as cleaning wipes are able to trap and retain polymer debris within their pores. Impregnation of an oil-in-water emulsion as cleaning agent lowers the interfacial tension between debris and the optical fiber thereby enabling the straightforward removal of polymer debris from the optical fiber. EXPERIMENTS: Electrospun membranes of poly(ethylene terephthalate) (PET) and cellulose acetate (CA) were obtained with fiber diameters of 0.430 µm and 2 µm respectively. The oil-in-water emulsion was formulated with 10 wt% medium chain triglyceride (MCT) and 10 wt% Tween 80 surfactant in an aqueous phosphate buffer solution. FINDINGS: In a scoring range from 0 to 5 for which the score 0 indicated superior cleaning and the score 5 referred to the least efficient cleaning, the electrospun fiber mats (without emulsion) scored within the range of 2-4 while emulsion impregnated electrospun fiber mats revealed the best score of 0. A drastic improvement was thus clearly evident from the obtained results when the cleaning emulsion was applied. The materials developed herein thus represent a new class of soft cleaning agents for optical fibers.

Multilayered Magnetic Gelatin Membrane Scaffolds.

A versatile approach for the design and fabrication of multilayer magnetic scaffolds with tunable magnetic gradients is described. Multilayer magnetic gelatin membrane scaffolds with intrinsic magnetic gradients were designed to encapsulate magnetized bioagents under an externally applied magnetic field for use in magnetic-field-assisted tissue engineering. The temperature of the individual membranes increased up to 43.7 °C under an applied oscillating magnetic field for 70 s by magnetic hyperthermia, enabling the possibility of inducing a thermal gradient inside the final 3D multilayer magnetic scaffolds. On the basis of finite element method simulations, magnetic gelatin membranes with different concentrations of magnetic nanoparticles were assembled into 3D multilayered scaffolds. A magnetic-gradient-controlled distribution of magnetically labeled stem cells was demonstrated in vitro. This magnetic biomaterial-magnetic cell strategy can be expanded to a number of different magnetic biomaterials for various tissue engineering applications.

Surface decorated poly(ester-ether-urethane)s nanoparticles: a versatile approach towards clinical translation.

Poly(ester-ether-urethane)s copolymers are a resourceful class of biopolymers for the preparation of nanocarriers for drug delivery applications. However, a simple clinical translation for this synthetic material with biological and quality features is still needed. In this view, poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers were synthesized as semi-bulk pilot (Kg) scale under mild conditions in absence of catalyst, bearing functional termini such as fluorescein tag and anticancer targeting moieties. The obtained materials were processed into surface decorated paclitaxel (PTX) loaded nanoparticles (NPs). The NPs were fully characterized in vitro and in vivo biodistribution in healthy mice evidenced no sign of toxicity and lower levels of PTX in lung and spleen, compared to clinically applied PTX dosage form.