Ecological weed management and square planting influenced the weed management, and crop productivity in direct-seeded rice.

Herbicide use may pose a risk of environmental pollution or evolution of resistant weeds. As a result, an experiment was carried out to assess the influence of different non-chemical weed management tactics (one hoeing (HH) at 12 DAS followed by (fb) one hand weeding at 30 DAS, one HH at 12 DAS fb Sesbania co-culture and its mulching, one HH at 12 DAS fb rice straw mulching @ 4t ha-1, one HH at 12 DAS fb rice straw mulching @ 6 t ha-1) on weed control, crop growth and yield, and economic returns in direct-seeded rice (DSR). Experiment was conducted during kharif season in a split-plot design and replicated thrice. Zero-till seed drill-sown crop (PN) had the lowest weed density at 25 days after sowing (DAS), while square planting geometry (PS) had the lowest weed density at 60 DAS. PS also resulted in a lower weed management index (WMI), agronomic management index (AMI), and integrated weed management index (IWMI), as well as higher growth attributes, grain yield (4.19 t ha-1), and net return (620.98 US$ ha-1). The cultivar Arize 6444 significantly reduced weed density and recorded higher growth attributes, yield, and economic return. In the case of weed management treatments, one HH at 12 DAS fb Sesbania co-culture and its mulching had the lowest weed density, Shannon-weinner index and eveness at 25 DAS. However, one hoeing at 12 DAS fb one hand weeding at 30 DAS (HH + WH) achieved the highest grain yield (4.85 t ha-1) and net returns (851.03 US$ ha-1) as well as the lowest weed density at 60 DAS. PS × HH + WH treatment combination had the lowest weed persistent index (WPI), WMI, AMI, and IWMI, and the highest growth attributes, production efficiency, and economic return.

Emerging ROS-Modulating Technologies for Augmentation of the Wound Healing Process.

Reactive oxygen species (ROS) is considered a double-edged sword. The slightly elevated level of ROS helps in wound healing by inhibiting microbial infection. In contrast, excessive ROS levels in the wound site show deleterious effects on wound healing by extending the inflammation phase. Understanding the ROS-mediated molecular and biomolecular mechanisms and their effect on cellular homeostasis and inflammation thus substantially improves the possibility of exogenously augmenting and manipulating wound healing with the emerging antioxidant therapeutics. This review comprehensively delves into the relationship between ROS and critical phases of wound healing and the processes underpinning antioxidant therapies. The manuscript also discusses cutting-edge antioxidant therapeutics that act via ROS scavenging to enhance chronic wound healing.

Engineering immunity via skin-directed drug delivery devices.

Extensive research is underway to discover a safe and effective vehicle to deliver the vaccines at the desired cutaneous site. These efforts majorly comprise the development of a fit-to-purpose vehicle for in-situ intracutaneous vaccine delivery for achieving the systemic cellular and humoral response to combat infectious diseases. Advancements in nanoscience, bioengineering, and skin science provided much support to vaccine adjuvant development. However, the bench-to-bed side translation of vaccines is still unsatisfactory. A skilfully designed vaccine delivery program aiming to translate the product into market use must address safety, efficacy, scaleup, reproducibility, cost of production, self-administrative potential, and regulatory concerns. This review provides deep insights into skin immunization approaches like mucosal vaccines, cellular/molecular immunological responses, and antigen-adjuvant combinations in modulating immunity. Further, the manuscript discusses distinct vaccine delivery systems used to date for engineering skin immunization, including microparticles, nanoparticles, spherical nucleic acids, STAR particles, niosomes, dendrimers, ethosomes, liposomes, and microneedles. The manuscript will interest researchers working towards developing a next-generation fit-to-purpose vehicle for intracutaneous vaccine delivery.

Recent advancements and future submissions of silica core-shell nanoparticles.

The core-shell silica-based nanoparticles (CSNPs) possess outstanding properties for developing next-generation therapeutics. CSNPs provide greater surface area owing to their mesoporous structure, which offers a high opportunity for surface modification. This review highlights the potential of core-shell silica-based nanoparticle (CSNP) based injectable nanotherapeutics (INT); its role in drug delivery, biomedical imaging, light-triggered phototherapy, Plasmonic enhancers, gene delivery, magnetic hyperthermia, immunotherapy, and potential as next-generation theragnostic. Specifically, the conceptual crosstalk on modern synthetic strategies, biodistribution profiles with a mechanistic view on the therapeutics loading and release modeling are dealt in detail. The manuscript also converses the challenges associated with CSNPs, regulatory hurdles, and their current market position.

Biosimilars accessible in the market for the treatment of cancer.

Biosimilars are the biological product clinically identical to a biologic reference standard regarding their strength, purity, and safety. A large segment of biosimilars has been developed for the treatment of cancer. This review aims to discuss various facets of biosimilars and explicates on biosimilars accessible in the market for cancer clinical intervention. It also illustrates the outcomes of recent clinical trial studies concerning biosimilars. Further, it also crosstalk the safety profiles, regulatory approval requirements, and allied challenges therein. The work will be of significant interest to researchers working in the field of biologics and biosimilars.

Nanomedicines accessible in the market for clinical interventions.

Nanomedicines refers to nanotechnology inspired pharmaceutical products often referred to as 'nanopharmaceuticals.' It has displayed commendable potential in enhancing therapeutic efficacy as well as in reducing the side effects associated with conventional drug counterpart. Recent years have monitored the entry of a large amount of nanomedicine in the market with an appreciable market share to date. Despite this, the development of nanomedicine is posing challenges (i.e., safety, regulatory hurdles, cost, scale-up issues, etc.) that need to be resolved for their market entry. This review presents a cross-sectional discussion on the nanomedicine-derived products available in the market for both clinical and diagnostic applications. An overview of its market potential, market size, and the products that are currently in the clinical stages is also provided. The review also expounds on the challenges faced by nano-drug products at the time of their commercialization.

99mTc-labelled and pH-awakened microbeads entrapping surface-modified lipid nanoparticles for the augmented effect of oxaliplatin in the therapy of colorectal cancer.

AIM: This study was aimed to develop Eudragit S100-coated, pH-awakened microbeads (MBs) encapsulating folic acid (FA)-modified tristearin solid lipid nanoparticles (SLNs) loaded with oxaliplatin (OP). Afterward, these formulations were evaluated (in vitro and in vivo) for their potential against colorectal cancer (CRC). METHODS: The SLNs were synthesised by employing the solvent diffusion technique and then they were entrapped in the MBs. The prepared uncoupled and coupled SLNs (SLN-OP and FA-SLN-OP, respectively) were examined for in vitro cytotoxicity effect against COLO-205. Gamma-scintigraphy study was used for determining biodistribution (in vivo) of drug in different organs through MBs. RESULTS: Outcomes for FA-SLN-OP revealed more cytotoxicity (50% inhibitory concentration [IC50] = 6.8 µg/ml) against COLO-205 cells (in vitro) than OP solution (IC50 = 8.0 µg/ml) and SLN-OP (IC50= 7.5 µg/ml). MBs were also investigated in vivo using Gamma-scintigraphy study. After 48 h study, 99mTc-EuB-FA-SLN-OP confirmed an elevated level of drug in the colonic tumour, which was found significantly (p< 0.0001) higher than that of 99mTc-EuB-SLN-OP. CONCLUSIONS: In conclusion, developed MBs formulation (99mTc-EuB-FA-SLN-OP) suggested promising results against therapy of CRC using dual targeting (i.e. ligand-directed and pH-awakened) approach.

Development of Metronidazole Loaded Chitosan Nanoparticles Using QbD Approach-A Novel and Potential Antibacterial Formulation.

The aim of this study was to design, optimize, and develop metronidazole (Met) loaded nanoparticles (MetNp) by employing quality-based design (QbD) as well as a risk assessment methodology. A fractional factorial design was used by selecting five independent variables viz., chitosan concentration, tripolyphosphate concentration, and acetic acid concentration as material attributes, stirring speed, and stirring time as process parameters, whereby their influence on two dependent variables such as particle size (PS) and %entrapment efficiency (%EE) was studied. MetNp were synthesized by employing an ionic-gelation technique and optimized formula obtained from the QbD design study. PS and %EE studies revealed the formation of MetNp with 558.06 ± 2.52 nm and 59.07 ± 2.15%, respectively. Furthermore, a Met release study in various simulated gastro-intestinal media suggested pH-triggered (pH > 7.0) and sustained release profile of Met from Eudragit S100 enteric-coated MetNp capsule (MetNp cap). Moreover, the stability investigation of formulations confirmed good stability with respect to their PS and residual drug content (RDC) at different temperature conditions. In conclusion, the QbD method was effectively utilized in the development of MetNp and enteric-coated MetNp cap depicting their potential to release Met through MetNp cap only in the colon region and can be utilized for the treatment of amoebiasis in the colon.

Expedition of Eudragit® Polymers in the Development of Novel Drug Delivery Systems.

Eudragit® polymer has been widely used in film-coating for enhancing the quality of products over other materials (e.g., shellac or sugar). Eudragit® polymers are obtained synthetically from the esters of acrylic and methacrylic acid. For the last few years, they have shown immense potential in the formulations of conventional, pH-triggered, and novel drug delivery systems for incorporating a vast range of therapeutics including proteins, vitamins, hormones, vaccines, and genes. Different grades of Eudragit® have been used for designing and delivery of therapeutics at a specific site via the oral route, for instance, in stomach-specific delivery, intestinal delivery, colon-specific delivery, mucosal delivery. Further, these polymers have also shown their great aptitude in topical and ophthalmic delivery. Moreover, available literature evidences the promises of distinct Eudragit® polymers for efficient targeting of incorporated drugs to the site of interest. This review summarizes some potential researches that are being conducted by eminent scientists utilizing the distinct grades of Eudragit® polymers for efficient delivery of therapeutics at various sites of interest.

Oral delivery of pH-responsive alginate microbeads incorporating folic acid-grafted solid lipid nanoparticles exhibits enhanced targeting effect against colorectal cancer: A dual-targeted approach.

To achieve an enhanced anticancer effect of drug to treat colorectal cancer, a dual-targeted (i.e., ligand-tailored and pH-triggered) multiparticulate system has been designed to deliver drug directly into the colon domain. In this regard, folic acid-grafted solid lipid nanoparticles (SLNs) bearing irinotecan were encapsulated in microbeads of alginates. Afterward, these microbeads were coated with enteric polymer (i.e., Eudragit S100) to make them pH-responsive. COLO-205 cells were used to determine in vitro cytotoxicity potential of various formulations. Findings for IHT loaded FA-coupled SLNs suggested significantly (p < 0.05) higher cytotoxic effect against COLO-205 cells (in vitro) as compared to drug solution and uncoupled SLNs. Further, the microbeads incorporating SLNs were evaluated for drug release in various simulated gastrointestinal fluids (i.e., pH, 1.2, 4.5, 7.4, and 6.8). Findings confirmed the release of the drug in the intestinal region only (i.e., pH > 7.0). In therapeutic experiments (in vivo), the optimized radiolabeled microbeads (99mTc-EuBIRSLN3 and 99mTc-EuBIRSLNF3) were administered via oral route to Balb/c mice. The results suggested that FA-coupled microbeads (99mTc-EuBIRSLNF3) distributed higher (19.62 ± 0.78%) amount of drug (i.e., 99mTc-IHT/g of tissue) as compared to uncoupled microbeads (99mTc-EuBIRSLN3, 7.63 ± 0.49%) in the colon tumor after 48 h, which confirmed its targeting ability to the tumor in the colon region. Further, 99mTc-EuBIRSLNF3 showed significantly (p < 0.01) higher antitumor effect against HT-29 cells bearing Balb/c mice over uncoupled microbeads and advocated their potential for enhanced antitumor efficacy for the treatment of colorectal cancer.

Nanotechnology-based Targeting of Neurodegenerative Disorders: A Promising Tool for Efficient Delivery of Neuromedicines.

Traditional drug delivery approaches remained ineffective in offering better treatment to various neurodegenerative disorders (NDs). In this context, diverse types of nanocarriers have shown their great potential to cross the blood-brain barrier (BBB) and have emerged as a prominent carrier system in drug delivery. Moreover, nanotechnology-based methods usually involve numerous nanosized carrier platforms, which potentiate the effect of the therapeutic agents in the therapy of NDs especially in diagnosis and drug delivery with negligible side effects. In addition, nanotechnology-based techniques have offered several strategies to cross BBB to intensify the bioavailability of drug moieties in the brain. In the last few years, diverse kinds of nanoparticles (NPs) have been developed by incorporating various biocompatible components (e.g., polysaccharide-based NPs, polymeric NPs, selenium NPs, AuNPs, protein-based NPs, gadolinium NPs, etc.), that showed great therapeutic benefits against NDs. Eventually, this review provides deep insights to explore recent applications of some innovative nanocarriers enclosing active molecules for the efficient treatment of NDs.

Lipid-based Nanoplatforms in Cancer Therapy: Recent Advances and Applications.

Though modern available cancer therapies are effective, they possess major adverse effects, causing non-compliance to patients. Furthermore, the majority of the polymeric-based medication platforms are certainly not universally acceptable, due to their several restrictions. With this juxtaposition, lipid-based medication delivery systems have appeared as promising drug nanocarriers to replace the majority of the polymer-based products because they are in a position to reverse polymer as well as, drug-associated restrictions. Furthermore, the amalgamation of the basic principle of nanotechnology in designing lipid nanocarriers, which are the latest form of lipid carriers, has tremendous chemotherapeutic possibilities as tumor-targeted drug-delivery pertaining to tumor therapy. Apart from this, it is reported that nearly 40% of the modern medication entities are lipophilic. Moreover, research continues to be efficient in attaining a significant understanding of the absorption and bioavailability of the developed lipids systems.

Solid Lipid Nanoparticles: A Promising Nanomaterial in Drug Delivery.

The solid lipid nanoparticles (SLNs) usually consists of active drug molecules along with solid lipids, surfactants, and/or co-surfactants. They possess some potential features such as nano-size, surface with a free functional group to attach ligands, and as well they prove safe homing for both lipophilic as well as hydrophilic molecules. As far as synthesis is concerned, SLNs can be prepared by employing various techniques viz., homogenization techniques (e.g., high-pressure, high-speed, cold, or hot homogenization), spray drying technique, ultrasonication, solvent emulsification, double emulsion technique, etc. Apart from this, they are characterized by different methods for determining various parameters like particle-size, polydispersity-index, surface morphology, DSC, XRD, etc. SLNs show good stability as well as the ability for surface tailoring with the specific ligand, which makes them a suitable candidate in the therapy of numerous illnesses, especially in the targeting of the cancers. In spite of this, SLNs have witnessed their application via various routes e.g., oral, parenteral, topical, pulmonary, rectal routes, etc. Eventually, SLNs have also shown great potential for delivery of gene/DNA, vaccines, as well as in cosmeceuticals. Hence, SLNs have emerged as a promising nanomaterial for efficient delivery of various Active Pharmaceutical Ingredients (APIs).

Irinotecan hydrochloride trihydrate loaded folic acid-tailored solid lipid nanoparticles for targeting colorectal cancer: development, characterization, and in vitro cytotoxicity study using HT-29 cells.

Aim: The aim of this investigation was to evaluate the potential of folic acid-tailored solid lipid nanoparticles (SLNs) for encapsulation as well as for in vitro cytotoxicity study of irinotecan hydrochloride trihydrate (IHT) against colorectal cancer (CRC) by using HT-29 cells. Methods: Solvent diffusion technique was employed for the preparation of SLNs. Further, the formulations were optimised via three-level, three-factor Box-Behnken design (BBD). Results: The uncoupled SLNs (IRSLNs) and folic acid-coupled SLNs (IRSLNFs) formulations revealed not only high %entrapment efficiency but also small particle size. Moreover, in vitro drug release results from IRSLNs and IRSLNFs confirmed that they followed sustained-release effect for up to 144 h. Whereas, in vitro cell viability study against HT-29 cell line suggested significantly (p < 0.05) higher cytotoxicity (IC50 = 15 µg/ml) of IRSLNFs over IRSLNs and IHT solution. Conclusions: Outcomes suggested that the engineered IRSLNFs hold great potential for targeting CRC for an extended period of time.

Colorectal cancer-targeted delivery of oxaliplatin via folic acid-grafted solid lipid nanoparticles: preparation, optimization, and in vitro evaluation.

OBJECTIVE: Colorectal cancer (CRC) ranked second in females and third in males among all type of cancers diagnosed. About 1.4 million cases took place with 693,900 deaths in 2012. It can occur either in colon or rectum. Thus, we aimed to develop and optimize oxaliplatin (OP) loaded solid lipid nanoparticles (SLNs). MATERIALS AND METHODS: SLNs containing tristearin, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), Lipoid S75, and Tween 80 was developed. Box-Behnken design was applied for optimization of SLNs and optimized formulation was selected for conjugation with folic acid (FA). Optimized formulations were evaluated for various physiochemical parameters viz., particle size (PS), zeta potential, %entrapment efficiency (EE), morphology, X-ray diffraction (XRD), and differential scanning calorimetry (DSC). RESULTS AND DISCUSSION: OP loaded uncoupled SLNs (OPSLNs) and OP loaded FA coupled SLNs (OPSLNFs) formulations revealed good EE, 49.2 ± 0.38% and 43.5 ± 0.59%, respectively and small PS, 146.2 ± 4.4 nm, and 158.8 ± 5.6 nm, respectively. XRD pattern and DSC results confirmed that OP was uniformly distributed in amorphous form within SLNs. In vitro drug release study of OPSLNs and OPSLNFs formulation revealed sustained drug release pattern of OP for up to 6 d. Anticancer activity on HT-29 cell line indicated the highest potency of OPSLNFs as compared to OPSLNs and OP solution. CONCLUSION: The present work illustrated the higher sensitivity of HT-29 cells to the drug entrapped in OPSLNFs as compared to OPSLNs and OP solution. Hence, this novel strategy might be a promising approach for the management of CRC.

Acyclovir-loaded sorbitan esters-based organogel: development and rheological characterization.

Herein, a nanoemulsion-based organogel (NEOG) system loaded with acyclovir has been developed for the effective treatment of herpes simplex virus infection via topical delivery. Pseudo-ternary phase diagram exhibited increase in non-birefrigent, optically isotropic region of organogel with Smix (Kw) ratio. The NEOG C showed good storage (G') and loss moduli (G″), and more compact network structures. Gel-sol transition temperature (Tg) and fractal dimension (Df) of NEOG system revealed increased density of the tubular network with Kw. Hence, high gelling ability of the developed NEOG system may attribute to the combination of sustained and site-specific delivery of drugs.

A novel sustained release drug-resin complex-based microbeads of ciprofloxacin HCl.

Objective A novel multiparticulate system for the gastro-mucoadhesive delivery of ciprofloxacin HCl (CFN) was developed with the help of ion-exchange resin to deal with urinary tract (UT) infections effectively. Materials and methods An optimized complex (resinate) of CFN with sodium polystyrene sulfonate USP resin was prepared and entrapped within microbeads of sodium alginate and pectin. The developed systems were evaluated for drug entrapment efficiency, percentage of mucoadhesion and in vitro release patterns in simulated gastric fluid (pH 1.2). Results and discussion The interaction of the resin complex and polycation via alginate was consequently supported the formation of polyelectrolyte complex membrane. The in vitro drug release studies demonstrate that formulation without drug-resin complex (NRB) released the drug more swiftly than formulation containing drug-resin complex (DRC). This controlled release pattern of drug, resin complex containing microbeads was owed to complexation between drug and resin. Conclusion Preliminary results from the study suggested that this drug-resin complex-entrapped microbeads can be used to incorporate other antibiotic drugs and could be effective against UT infection. Such developed formulation could be subjected to in vivo studies in future in order to prove their efficacy for such type of infections.

Development and in vitro characterization of a multiparticulate delivery system for acyclovir-resinate complex.

CONTEXT: Herpes viruses cause threatening infections in humans and stand second as causative agents for most human viral diseases, after influenza and cold viruses. OBJECTIVE: A novel multiparticulate delivery system for acyclovir (ACV), based on ion-exchange resin, was developed to achieve a gastro-mucoadhesive effect in order to effectively combat the herpes simplex virus. MATERIALS AND METHODS: A combination of ACV and cholestyramine resin was optimized and further entrapped within sodium alginate and Carbopol microbeads. The developed systems were evaluated for drug entrapment efficiency (DEE), percentage of mucoadhesion, and in vitro release characteristics in simulated gastric fluid (SGF, pH 1.2). RESULTS: With the aid of scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR), the interaction of the resinate and polycations with alginate has been revealed, which consequently supports the formation of the membrane by the polyelectrolyte complex. The in vitro drug release studies demonstrate that formulations without the drug-resin complex (DRC) released the drug more rapidly than formulations containing DRC, which released the drug in a controlled manner, due the formation of a complex between drug and resin. DISCUSSION AND CONCLUSION: Preliminary results from this study suggest that these DRC-entrapped microbeads may be used to incorporate other antiviral drugs and could be effective against infections caused by herpes viruses. Such formulations developed could be subjected to in vivo studies in future, in order to prove complete clearance of herpes infections.