Engineering Platelet Membrane Imitating Nanoparticles for Targeted Therapeutic Delivery.

Platelet membrane imitating nanoparticles (PMINs) is a novel drug delivery system that imitates the structure and functionality of platelet membranes. PMINs imitate surface markers of platelets to target specific cells and transport therapeutic cargo. PMINs are engineered by incorporating the drug into the platelet membrane and encapsulating it in a nanoparticle scaffold. This allows PMINs to circulate in the bloodstream and bind to target cells with high specificity, reducing off-target effects and improving therapeutic efficacy. The engineering of PMINs entails several stages, including the separation and purification of platelet membranes, the integration of therapeutic cargo into the membrane, and the encapsulation of the membrane in a nanoparticle scaffold. In addition to being involved in a few pathological conditions including cancer, atherosclerosis, and rheumatoid arthritis, platelets are crucial to the body's physiological processes. This study includes the preparation and characterization of platelet membrane-like nanoparticles and focuses on their most recent advancements in targeted therapy for conditions, including cancer, immunological disorders, atherosclerosis, phototherapy, etc. PMINs are a potential drug delivery system that combines the advantages of platelet membranes with nanoparticles. The capacity to create PMMNs with particular therapeutic cargo and surface markers provides new possibilities for targeted medication administration and might completely change the way that medicine is practiced. Despite the need for more studies to optimize the engineering process and evaluate the effectiveness and safety of PMINs in clinical trials, this technology has a lot of potential.

Engineered Bacteria: General Overview as Therapeutic Agent and a Novel Drug Delivery System.

Bacterial engineering modifies bacteria's genomic sequence using genetic engineering tools. These engineered bacteria can produce modified proteins, peptides, nucleic acids, and other biomolecules that can be used to treat various medical conditions. Engineered bacteria can target diseased tissues or organs, detect specific biomarkers in the diseased environment, and even induce specific conditions. Furthermore, a meticulously designed intracellular metabolic pathway can activate or inhibit the expression of related genes, synthesise biologically active therapeutic molecules, and precisely deliver drug payloads to diseased tissues or organs. Lactococcus (L. lactis), Salmonella (S. typhi), and E. coli (E. coli Nissle) are the most studied engineered microorganisms used as drug carriers. These have been used in vaccines to treat multifactorial diseases such as cancer, autoimmune diseases, metabolic diseases, and inflammatory conditions. Other promising strains include Bifidobacterium animalis, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus lugdunensis, and Clostridium sporogenes. Despite the low reported risk, toxic effects associated with bacterial cells, limiting their efficacy and rapid clearance due to immune responses stimulated by high bacterial concentrations, remain major drawbacks. As a result, a better and more effective method of drug delivery must be developed by combining bacterial-based therapies with other available treatments, and more research in this area is also needed.

Microbubbles Contrast Agents: General Overview as Diagnostics and Therapeutic Agent.

Recent discoveries have unfolded many powerful emerging applications in the field of drug delivery science. For the past few years, ultrasound mediated microbubble contrast agents have been an emerging modality for diagnostic and drug delivery applications. Microbubbles are small spherical bubbles composed of a gas core encapsulated by a shell with different materials. The composition of the microbubble determines its stiffness, encapsulation efficiency, stability, and clearance from the system. A gas-filled microbubble, when activated by an acoustic pulse, can produce large volumetric oscillations and, once administered intravenously, can act as a cavitating nuclei, allowing for a wide range of ultrasound-assisted drug delivery applications. Microbubbles offer a fantastic approach to ultrasound triggered drug delivery with various drug loading techniques and targeting strategies for the uptake of bioactive substances such as polynucleotides, proteins, genes, and small-molecule drugs. Microbubbles can be used for several diagnostic and therapeutic purposes for accurate detection and treatment of various life-threatening diseases.

Genome-Wide SNP Discovery and Mapping QTLs for Seed Iron and Zinc Concentrations in Chickpea (Cicer arietinum L.).

Biofortification through plant breeding is a cost-effective and sustainable approach towards addressing micronutrient malnutrition prevailing across the globe. Screening cultivars for micronutrient content and identification of quantitative trait loci (QTLs)/genes and markers help in the development of biofortified varieties in chickpea (Cicer arietinum L.). With the aim of identifying the genomic regions controlling seed Fe and Zn concentrations, the F2:3 population derived from a cross between MNK-1 and Annigeri 1 was genotyped using genotyping by sequencing approach and evaluated for Fe and Zn concentration. An intraspecific genetic linkage map comprising 839 single nucleotide polymorphisms (SNPs) spanning a total distance of 1,088.04 cM with an average marker density of 1.30 cM was constructed. By integrating the linkage map data with the phenotypic data of the F2:3 population, a total of 11 QTLs were detected for seed Fe concentration on CaLG03, CaLG04, and CaLG05, with phenotypic variation explained ranging from 7.2% (CaqFe3.4) to 13.4% (CaqFe4.2). For seed Zn concentration, eight QTLs were identified on CaLG04, CaLG05, and CaLG08. The QTLs individually explained phenotypic variations ranging between 5.7% (CaqZn8.1) and 13.7% (CaqZn4.3). Three QTLs for seed Fe and Zn concentrations (CaqFe4.4, CaqFe4.5, and CaqZn4.1) were colocated in the "QTL-hotspot" region on CaLG04 that harbors several drought tolerance-related QTLs. We identified genes in the QTL regions that encode iron-sulfur metabolism and zinc-dependent alcohol dehydrogenase activity on CaLG03, iron ion binding oxidoreductase on CaLG04, and zinc-induced facilitator-like protein and ZIP zinc/iron transport family protein on CaLG05. These genomic regions and the associated markers can be used in marker-assisted selection to increase seed Fe and Zn concentrations in agronomically superior chickpea varieties.

BCS class II drug loaded protein nanoparticles with enhanced oral bioavailability: in vitro evaluation and in vivo pharmacokinetic study in rats.

The aim of the study was to improve the bioavailability of atorvastatin calcium (ATC) by formulating polymeric nanoparticles (NPs) with an easy and cost-effective approach. ATC entrapped gelatin nanoparticles (AEGNPs) were prepared by using a simple one-step desolvation method. The formed NPs were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Morphological study exhibited a homogenous spherical shape of formulated NPs. FTIR studies revealed the chemical compatibility of the drug with gelatin. The improvement in drug delivery kinetics of AEGNPs could be attributed to amorphization along with the reduction in particle size of ATC. The pharmacokinetic study in Sprague-Dawley rats revealed that the Cmax and AUC0-24 of AEGNPs in rats were ∼4-fold and ∼11-fold higher than that of pure ATC suspension. The research presented successfully shows that AEGNPs preparation by one-step desolvation, using minimum excipients is a quick, easy and reproducible method. These results suggest that the ATC encapsulated gelatin NP is a promising approach for the oral delivery of ATC, improving the bioavailability of the drug.

Cubosomes: Innovative Nanostructures for Drug Delivery.

BACKGROUND: Some amphiphilic lipids can self-assemble to form bicontinuous cubic liquid crystalline materials in aqueous media. These cubic structures have gained considerable attention since they impart unique properties of practical interest. Cubosomes, being dispersions of an inverted type bicontinuous cubic phase, separate two continuous aqueous regions with a lipid bilayer having the propensity to incorporate drugs of varying polar characteristics. These novel versatile materials possess the properties to form a section of the next generation of advanced biocompatible nanoparticles. METHODS: This review chiefly considers the scope and importance of cubosomes as a proficient drug delivery vehicle. In addition, it also takes into account the various methods of preparation, the drug loading and release behavior as well as different methods of characterization. Their current advances in various arenas ranging from sustained drug release, burn management, melanoma therapy, vaccine delivery, protein delivery, cosmeceutical and theranostic applications are briefly summarized in this overview. RESULTS: The drug release from cubosomal dispersions have shown enhancement in bioavailability by solubilisation of poorly water soluble drugs, decrease in adverse effects, enhancement of intracellular penetration, protection against degradation, possibility of sustained drug release and the biodegradable nature of lipids is an added advantage. CONCLUSION: Recognizing the desirable properties of cubosomes, it has been proposed as a novel carrier for drug delivery systems. Their unique solubilizing, encapsulating, transporting and protecting capabilities make them an attractive vehicle for numerous in vivo drug delivery routes.

Nanodiamonds as a new horizon for pharmaceutical and biomedical applications.

A palpable need for the optimization of therapeutic agents, due to challenges tackled by them such as poor pharmacokinetics and chemoresistance, has steered the journey towards novel interdisciplinary scientific field for emergence of nanostructure materials as a carrier for targeted delivery of therapeutic agents. Amongst various nanostructures, nanodiamonds are rapidly rising as promising nanostructures that are suited especially for various biomedical and imaging applications. Advantage of being biocompatible and ease of surface functionalization for targeting purpose, besides safety which are vacant by nanodiamonds made them a striking nanotool compared to other nonmaterials which seldom offer advantages of both functionality as well as safety. This review outlines the summary of nanodiamonds, regarding their types, methods of preparation, and surface modification. It also portrays the potential applications of nanodiamond as targeted drug delivery of various bioactive agents. Based on photoluminescent and optical property, nanodiamonds are envisioned as an efficient bioimaging nanostructure. Nanodiamonds as a novel platform hold great promise for targeting cancer cells and in-vivo cell imaging. Based upon their inimitable properties and applications nanodiamonds propose an exciting future in field of therapeutics and thus possess vibrant opportunities.

Cyclodextrin-based nanosponges: a propitious platform for enhancing drug delivery.

INTRODUCTION: Recently, Nanotechnology is receiving considerable acknowledgment due to its potential to combine features that are difficult to achieve by making use of a drug alone. Cyclodextrin-based nanosponges are yet another contemporary approach for highlighting the advancements which could be brought about in a drug delivery system. Statistical analyses have shown that around 40% of currently marketed drugs and about 90% of drugs in their developmental phase encounter solubility-related problems. Cyclodextrin-based nanosponges have the capacity to emerge as a productive approach over conventional cyclodextrins by overcoming the disadvantages associated with the latter. AREAS COVERED: This review is intended to give an insight regarding cyclodextrin-based nanosponges such as their physical and chemical properties. In addition, methods of preparation and characterization are discussed along with biocompatibility, and how these nanomeric elements can be exploited in developing effective drug formulations. EXPERT OPINION: This emerging technology of cyclodextrin-based nanosponges is expected to provide technical solutions to the formulation arena and to come up with some successful products in the pharmaceutical market. It also has an exciting future in the field of therapeutics wherein it can cater site-directed drug delivery and hence it possesses vibrant opportunities.

Aptamer-dendrimer bioconjugate: a nanotool for therapeutics, diagnosis, and imaging.

INTRODUCTION: Aptamers hold great promise as molecular tool in biomedical applications due to the therapeutic utility exhibited by their target specificity and sensitivity. Although current development of aptamer is hindered by its probable in vivo degradation, inefficient immobilization on probe surface, and generation of low detection signal, bioconjugation with nanomaterials can feasibly solve these problems. Nanostructures such as dendrimers, with multivalency and nonimmunogenicity, bioconjugated with aptamers have opened newer vistas for better pharmaceutical applications of aptamers. AREAS COVERED: This review covers brief overview of aptamers and dendrimers, with specific focus on recent progresses of aptamer-dendrimer (Apt-D) bioconjugate in areas of targeted drug delivery, diagnosis, and molecular imaging along with the discussion on the currently available conjugates, using their in vitro and in vivo results. EXPERT OPINION: The novel Apt-D bioconjugates have led to advances in targeting cancer cell, have amplified biosensing, and offered in vivo cell imaging. Because of the unique properties and applications, Apt-D bioconjugate propose an exciting future. However, further research in synthesis of new target-specific aptamers and their conjugation with dendrimers is required to establish full potential of Apt-D bioconjugate.

Formulation and evaluation of lecithin organogel for topical delivery of fluconazole.

The purpose of the present study was to develop and investigate the suitability of microemulsion based lecithin organogel formulations for topical delivery of fluconazole in order to bypass its gastrointestinal adverse effects. The ternary phase diagrams were developed and various organogel formulations were prepared using pharmaceutically acceptable surfactant (lecithin) and ethyl oleate (EO). Solubility of fluconazole in EO and EO-lecithin reverse micellar system was determined. The transdermal permeability of fluconazole from different concentrations of lecithin organogels containing EO as oil phase was analyzed using Keshary-Chien diffusion cell through excised rat skin. Solubility of fluconazole in EO-lecithin reverse micellar system was almost 3 folds higher than that in EO. Gelation and immobilization of oil require critical solubility-insolubility balance of gelator. The occurrence of gel phase was lecithin concentration dependent and was observed in 10-60% w/v of system. Organogel containing 300 mM of lecithin showed the higher drug release and better relative consistency. Hence, it was selected for antifungal activity. The increase in antifungal activity of fluconazole in lecithin organogel may be because of the surfactant action of the lecithin and EO that may help in the diffusion of drug. The histopathological data showed that EO-lecithin organogels were safe enough for the topical purpose. Hence, the present lecithin based organogel appears beneficial for topical delivery of fluconazole in terms of easy preparation, safety, stability and low cost.

Evaluation of sublethal effects of dichlorvos upon Caenorhabditis elegans based on a set of end points of toxicity.

The primary objective of this study was to examine a possible correlation among the three endpoints of toxicity, namely, stress gene expression (hsp16), feeding, and acetylcholinesterase (AChE) activity in transgenic C. elegans (hsp16-lacZ) exposed to sublethal concentrations of dichlorvos, an organophosphorus insecticide. Worms exposed to dichlorvos (at 5, 40, and 80 microM) exhibited a concentration-dependent inhibition in feeding with total cessation in feeding occurring beyond 4 h of exposure. Concomitantly, marked and dose-dependent inhibition (69%-90%) of AChE was also evident after 4 h of exposure. Induction of heat shock protein (Hsp) was evident after 4 h of exposure (as seen from quantitative analysis), although maximum expression of Hsp was evident only after 24 h of exposure (as evident from qualitative analysis). Interestingly, the Hsp induction was restricted only to the pharyngeal region. Significant correlation was discernible between the three evaluated end points suggesting their possible interrelated role in the physiological dysfunctions evoked by sublethal concentrations of dichlorvos.

Development and in vitro evaluation of an oral floating matrix tablet formulation of diltiazem hydrochloride.

The purpose of this research was to prepare a floating drug delivery system of diltiazem hydrochloride (DTZ). Floating matrix tablets of DTZ were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by direct compression technique, using polymers such as hydroxypropylmethylcellulose (HPMC, Methocel K100M CR), Compritol 888 ATO, alone or in combination and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of sodium bicarbonate and succinic acid on drug release profile and floating properties were investigated. A 3(2) factorial design was applied to systematically optimize the drug release profile. The amounts of Methocel K100M CR (X1) and Compritol 888 ATO (X2) were selected as independent variables. The time required for 50% (t50) and 85% (t85) drug dissolution were selected as dependent variables. The results of factorial design indicated that a high level of both Methocel K100M CR (X1) and Compritol 888 ATO (X2) favors the preparation of floating controlled release of DTZ tablets. Comparable release profiles between the commercial product and the designed system were obtained. The linear regression analysis and model fitting showed that all these formulations followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). While tablet hardness had little or no effect on the release kinetics and was found to be a determining factor with regards to the buoyancy of the tablets.