Formulation of Cabotegravir Loaded Gold Nanoparticles: Optimization, Characterization to In-Vitro Cytotoxicity Study.

The effective and preventive treatment of HIV is one of the difficult challenges worldwide. It requires the development of an effective prophylactic strategy to prevent HIV/AIDS. This study aimed to synthesize Cabotegravir (CAB)-biodegradable gold (Au) nanoparticles by using pectin as a reducer and stabilizer. CAB-GNPs were prepared by the slightly modified Turkevich method. CAB-GNPs were optimized using Box Behnken design for independent variables gold chloride (A), pectin (B) and pH range (C). The effects of independent variables were observed on particle size (Y1) and encapsulation efficiency (Y2). The results of the study revealed that the optimized nanoparticles (GLN7) had a particle size of 3.9 ± 0.1 nm and encapsulation efficiency of 97.2 ± 3.9%. TEM study showed the spherical shape particles. The in-vitro drug release revealed 62.1 ± 0.5% release of CAB in simulated gastric buffer (pH 1.2) and 45.5 ± 2.8% in physiological buffer (pH 7.4). In-vitro cytotoxicity study and antibacterial activity depicted the safety of the prepared NPs by showing lesser toxicity than pure CAB. From the results, our experimental outcomes concluded that CAB gold nanoparticles composed of pectin may constitute a preferred embodiment for the delivery of CAB.

Dual engineered gold nanoparticle based synergistic prophylaxis delivery system for HIV/AIDS.

HIV is a pandemic and continuously raises problem across the world. This disease puts an immense pressure on treatment modalities. There are only few clinically accepted drugs available for the treatment and few molecules under clinical development. Although, the antiretroviral drugs give reliable and positive response on control of virus replication but during the long treatment, it has been affirmed that there are number of side effects. With recent advancements in biotechnology, nanomaterials such as gold and silver etc. are proving to be a game changer in targeted drug delivery treatment. As gold nanoparticles (AuNPs) are biocompatible natural excipients, a lot of scientists are very eager to investigate more about the immune effects of AuNPs to create a safe and cost effective treatment that could potentially help in the reduction of numerous toxic effects present in the existing treatments of various critical diseases like cancer and HIV etc. In this context, the present hypothesis recommends the use of combination drug delivery strategy based on gold nanoparticles that could pave the way to overcome adverse results of existing delivery techniques of antiretroviral drugs to treat HIV. This review also highlights the fact that a proper development of this gold nanoparticle combination antiretroviral drug delivery approach will not only help to suppress the virus multiplication but also target the viral entry area by attaching with gp120 (glycoprotein 120), and inhibit the binding with CD4 (Cluster of differentiation 4) T cells.

WITHDRAWN: Appraisal of Bone Targeting Potential of Nanohydroxyapatite Based Drug Carriers Conjugated with Pamidronate in Osteoporosis Treatment

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Emerging Role of CD44 Receptor as a Potential Target in Disease Diagnosis: A Patent Review.

BACKGROUND: The CD44 receptor is a cell surface glycoprotein, which mediates many physiological and pathological activities. Its key role is to provide defence against inflammatory reactions by cellular transmigration and cell signalling. In pathological conditions, it gives destructive outcomes by mediating migration of pathogenic cells to vital organs resulting in tissue and organ damage. It binds to several ligands principally the hyaluronan. OBJECTIVE: This review explores CD44 structure, functions, and its potential as a disease indicator and therapeutic target. METHOD: From a thorough literature review on the CD44 receptor, several patents of targeting approaches have been identified and herewith reviewed which recommend CD44-binding proteins, CD44-binding antibodies, antibody fragments, pharmaceutical compositions, as well as nucleic acids as a targeting moiety. RESULT: Applicability of CD44 overexpression and its targeting has now been extensively utilized in the disease diagnosis and real-time bio imaging of pathologic cells. CONCLUSION: A thorough understanding of CD44-receptor structure, expression and diverse functions towards different cell types would offer an opportunity to develop better therapeutic approaches in the near future by overcoming all the shortcomings of toxicity and efficacy. The present review includes recent patents of CD44 receptor targeting approaches that have been presented in the different agencies: European (EP), US, and World Intellectual Property Organization (WIPO) and a general analysis of the future developments and trends in this emerging area.

Synergistic anticancer efficacy of Bendamustine Hydrochloride loaded bioactive Hydroxyapatite nanoparticles: In-vitro, ex-vivo and in-vivo evaluation.

The present work evaluates the synergistic anticancer efficacy of bioactive Hydroxyapatite (HA) nanoparticles (HA NPs) loaded with Bendamustine HCl. Hydroxyapatite is a material with an excellent biological compatibility, a well-known fact which was also supported by the results of the Hemolytic studies and a high IC50 value observed in the MTT assay. HA NPs were prepared by the chemical precipitation method and loaded with the drug via physical adsorption. In-vitro release study was performed, which confirmed the sustained release of the drug from the drug loaded HA NPs. MTT assay, Cell Uptake and FACS studies on JURKAT E6.1 cell line and in-vivo pharmacokinetic studies in Wistar rats revealed that the drug loaded HA NPs could be easily internalized by the cells and release drug in a sustained manner. The drug loaded HA NPs showed cytotoxicity similar to the drug solution at 1/10th of the drug content, which indicates a possible synergism between the activity of the anticancer drug and calcium ions derived from the carrier. An increase in intracellular Ca(2+) ions is reported to induce apoptosis in cells. Tumor regression study in Balb/c mice Ehrlich's ascites model presented a similar synergistic efficacy. The drug solution was able to decrease the tumor volume by half, while the drug loaded HA NPs reduced the tumor size by 6 times.

Nanofacilitated synergistic treatment for rheumatoid arthritis: A 'three-pronged' approach.

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease of unidentified etiology that affects the joints and causes pain, swelling, stiffness and redness in the joints. The exact cause of rheumatoid arthritis has not yet been discovered and, consequently, treatment methods have not been optimally effective. It has long been treated with anti-inflammatory and immunosupressants including modern biologics either alone or in combination but all of the drugs have severe life threatening consequences with impaired immune function due to nonspecific targeting. Therefore, a three-pronged approach of local, active and synergistic targeting can be used to optimize delivery of therapeutic agents to reduce toxicity and patient outcome without compromising patient's immunity.

Revisiting bone targeting potential of novel hydroxyapatite based surface modified PLGA nanoparticles of risedronate: Pharmacokinetic and biochemical assessment.

Hydroxyapatite based biodegradable mPEG-PLGA nanoparticles of risedronate (mPEG-PLGA-RIS-HA) were prepared by water miscible dialysis method for synergistic treatment of osteoporosis. The bone targeting potential of prepared nanoparticles was evaluated by performing the cell viability study and protein estimation in pre-osteoblast cell line (MC3T3E1). Biochemical and in-vivo pharmacokinetic studies on osteoporotic rat model treated with different formulations were performed. Under the biochemical study ALP, TRAP, HxP and Calcium levels were determined. Osteoporotic model treated with prepared nanoparticles indicated significant effect on bone. Pharmacokinetic studies revealed 6-fold and 4-fold increase in the relative bioavailability after intravenous and oral administration of nanoparticles respectively as compared to marketed formulation confirming better effective drug transport. Biochemical investigations also showed a significant change in biomarker level which ultimately lead to bone formation/resorption. A stability analysis has also been carried out according to ICH guidelines (Q1AR2) and shelf life was found to be 1year and 4 months for the prepared formulation. Thus the results of present studies indicated that mPEG-PLGA-RIS-HA NPs has a great potential for sustained delivery of RIS for the treatment and prevention of osteoporosis and to minimize the adverse effects of RIS typically induced by its oral administration.

Design and Development of Bioceramic Based Functionalized PLGA Nanoparticles of Risedronate for Bone Targeting: In-vitro Characterization and Pharmacodynamic Evaluation.

PURPOSE: Bioceramic(Hydroxyapatite) based Poly(D,L-lactide-co-glycolide) (PLGA) and polyethylene glycol (PEG) nanoparticles of Risedronate was prepared by dialysis method for bone-targeting. METHODS: Risedronate, a targeting moiety that has a strong affinity for bone, was conjugated to PLGA via carbodiimide chemistry. Mono-methoxy PEG(mPEG)-PLGA block polymers were synthesized and used to impart surface hydrophilicity to nanoparticles to avoid its uptake by reticuloendothelial system (RES). The structure of prepared di block copolymers were characterized by FT-IR and NMR spectrometry. Risedronate was adsorbed on the surface of hydroxyapatite (RIS-HA) and it was conjugated with different ratios of mPEG-PLGA. The formation of surface-modified PLGA nanoparticle prepared with various ratios of risedronate as well as hydroxyapatite and mPEG was confirmed by (1)H NMR and FT-IR spectrometry. RESULTS: Size and % entrapment of the prepared nanoparticle was found to be 79.3 ± 2.3 nm and 93 ± 3.1%. Transmission electron microscopy (TEM) revealed that mPEG-PLGA-RIS-HA nanoparticles possess smooth and uniform surface. Pharmacodynamic study was performed on Dexamethasone (DEX) induced osteoporotic model. The effect of various formulations (mPEG-PLGA-RIS, mPEG-PLGA-RIS-HA and RISOFOS tablet) on bone was studied by Volume bone density (VBD) and by histopathological evaluation. Interestingly mPEG-PLGA-RIS-HA, showed a significant enhancement in bone micro-architecture when compared with other formulations. CONCLUSIONS: The results strongly implicated that mPEG-PLGA-RIS-HA has a therapeutic benefits over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model.