Cold kit for Rhenium-188 microspheres based selective intra-arterial therapy (SIRT): Preparation, characterization and feasibility study.

Selective-intra-arterial radionuclide therapy (SIRT) using radiolabeled microspheres are being widely employed for the delivery of therapeutic radioisotope to liver cancers by exploiting the dual blood supply to liver. It delivers the therapeutic radiations to tumor and spares the healthy liver. Several radiolabeled microspheres formulations, labelled with 90Y, are commercially available. However, high-cost leads to unaffordability for several patients. 188Re-based therapy seems affordable due to commercial availability of 188W/188Re generator that have long shelf-life of more than 6 months. To provide affordable solution, the microsphere cold kit with quick and facile methodology for 188Re radiolabeling has been developed. The microsphere cold kit has been characterized for their physicochemical properties. The Quality Control (QC) tests were also performed for clinical application. The feasibility studies were performed to study distribution and retention of 188Re microspheres in tumor. The results demonstrated that the developed cold kit enables facile and quick radiolabeling with 188Re. 188Re microspheres showed good retention in tumor and found suitable for SIRT.

Freeze-dried microspheres for selective intra-arterial radionuclide therapy: an affordable solution.

OBJECTIVE: Selective intra-arterial radionuclide therapy (SIRT) using radiolabelled microspheres is for the delivery of therapeutic radioisotope to liver cancers and thus, sparing healthy liver. Several radiolabelled microspheres are commercially available. The main issue associated with these microspheres is affordability. Re-188 is a generator produced radionuclide, emits high energy therapeutic beta particle and imageable gamma photons for pre- and post-therapy dosimetry. METHODS: Tc-99m/Re-188 labelled microspheres have been developed and quality control tests have been performed for suitable clinical use. The clinical studies with Re-188 microspheres for SIRT have been performed. Post-therapy images were acquired for dosimetry. RESULTS: The microspheres were found to possess spherical morphology of less than 20 µm size. The quality control revealed the suitability of microspheres for intravenous administration. The preliminary studies in thirty patients demonstrated good retention in tumor and high tumor to normal liver ratio. Re-188 microspheres were well tolerated by patients. Same microspheres labelled with either Tc-99m or Re-188 were used for pretherapy dosimetry and Re-188 labeled microspheres for therapy (SIRT) as a single-day procedure. CONCLUSION: The freeze-dried microspheres may emerge as highly cost-effective candidates for both pre-therapy dosimetry and SIRT and may benefit a large population with inoperable liver cancer.

A Facile Approach for Synthesis and Intracellular Delivery of Size Tunable Cationic Peptide Functionalized Gold Nanohybrids in Cancer Cells.

Peptide-based drug delivery systems have become a mainstay in the contemporary medicinal field, resulting in the design and development of better pharmaceutical formulations. However, most of the available reports employ tedious multiple reaction steps for the conjugation of bioactive cationic peptides with drug delivery vehicles. To overcome these limitations, the present work describes a one-step approach for facile and time efficient synthesis of highly cationic cell penetrating peptide functionalized gold nanoparticles and their intracellular delivery. The nanoconstruct was synthesized by the reduction of gold metal ions utilizing cell penetrating peptide (CPP), which facilitated the simultaneous synthesis of metal nanoparticles and the capping of the peptide over the nanoparticle surface. The developed nanoconstruct was thoroughly characterized and tested for intracellular delivery into HeLa cells. Intriguingly, a high payload of cationic peptide over gold particles was achieved, in comparison to conventional conjugation methods. Moreover, this method also provides the ability to control the size and peptide payload of nanoparticles. The nanoconstructs produced showed enhanced cancer cell penetration (µM) and significant cytotoxic effect compared to unlabeled gold nanoparticles. Therefore, this novel approach may also have significant future potential to kill intracellular hidden dreaded pathogens like the human immunodeficiency virus, Mycobacterium tuberculosis, and so forth.

A novel polyherbal microbicide with inhibitory effect on bacterial, fungal and viral genital pathogens.

A polyherbal cream (Basant) has been formulated using diferuloylmethane (curcumin), purified extracts of Emblica officinalis (Amla), purified saponins from Sapindus mukorossi, Aloe vera and rose water along with pharmacopoeially approved excipients and preservatives. Basant inhibits the growth of WHO strains and clinical isolates of Neisseria gonorrhoeae, including those resistant to penicillin, tetracycline, nalidixic acid and ciprofloxacin. It has pronounced inhibitory action against Candida glabrata, Candida albicans and Candida tropicalis isolated from women with vulvovaginal candidiasis, including three isolates resistant to azole drugs and amphotericin B. Basant displayed a high virucidal action against human immunodeficiency virus HIV-1NL4.3 in CEM-GFP reporter T and P4 (Hela-CD4-LTR-betaGal) cell lines with a 50% effective concentration (EC50) of 1:20000 dilution and nearly complete (98-99%) inhibition at 1:1000 dilution. It also prevented the entry of HIV-1(IIIB) virus into P4-CCR5 cells (EC50 approximately 1:2492). Two ingredients, Aloe and Amla, inhibited the transduction of human papillomavirus type 16 (HPV-16) pseudovirus in HeLa cells at concentrations far below those that are cytotoxic and those used in the formulation. Basant was found to be totally safe according to pre-clinical toxicology carried out on rabbit vagina after application for 7 consecutive days or twice daily for 3 weeks. Basant has the potential of regressing vulvovaginal candidiasis and preventing N. gonorrhoeae, HIV and HPV infections.