Rakhi Jha

An emerging interface between life science and nanotechnology: present status and prospects of reproductive healthcare aided by nano-biotechnology

Among the various applications of nano-biotechnology, healthcare is considered one of the most significant domains. For that possibility to synthesize various kind of nanoparticles (NPs) and the ever-increasing ability to control their size as well as structure, to improve surface characteristics and binding NPs with other desired curing agents has played an important role. In this paper, a brief sketch of various kinds of nanomaterials and their biomedical applications is given. Despite claims of bio-nanotechnology about to touch all areas of medical science, information pertaining to the role of nanotechnology for the betterment of reproductive healthcare is indeed limited. Therefore, the various achievements of nano-biotechnology for healthcare in general have been illustrated while giving special insight into the role of nano-biotechnology for the future of reproductive healthcare betterment as well as current achievements of nanoscience and nanotechnology in this arena.

Smart RISUG: a potential new contraceptive and its magnetic field-mediated sperm interaction.

The rationale and technique underlying a novel concept of noninvasive fertility control by a new Cuproferrogel contraceptive drug, iron oxide–copper–styrene maleic anhydride–dimethyl sulphoxide (Fe3O4–Cu–SMA–DMSO) composite named ‘Smart RISUG’ (smart reversible inhibition of sperm under guidance) in presence of pulsed magnetic field (PMF; 1 mT to 800 mT) is explained. It was synthesized by dispersing iron oxide particles and copper particles into SMA-DMSO (male contraceptive RISUG) and characterized for particle distribution, particle size measurement and transmittance peaks, etc. Interaction of the RISUG particles as well as Smart RISUG particles with Albino rat sperm cell was studied in presence as well as absence of PMF. To find an explanation to increased reaching of the Smart RISUG drug into sperm under influence of magnetic field, the transport properties were characterized by high resolution transmission electron microscopy and atomic force microscopy. Smart RISUG could be mobilized into sperm cell membrane at the PMF, 760 mT in about 50 seconds. Adoption of novel drug Smart RISUG involving new technique may open the pathway for non surgical control of drug distribution, detection and restoration of the normal fertility after removal of the contraceptive from the male/female reproductive tube in presence of electromagnetic field.

Correction: Dietary flavone chrysin (5,7-dihydroxyflavone ChR) functionalized highly-stable metal nanoformulations for improved anticancer applications

Nanomaterials of noble metals with unique size, shape and composition receives much attention owing to their versatile functionality in personalized cancer nanomedicine. Chrysin (ChR), a natural anticancer bioflavonoid, emerged as a potential drug therapy for almost all types of cancer, however it has poor solubility and bioavailability. Herein, we report a new approach to formulate biofunctionalized metallic silver (ChR–AgNPs) and gold (ChR–AuNPs) nanoparticles using ChR as a direct bioreductant and capping agent. Size and dispersity of nanoparticles (NPs) were controlled through fixing different reaction conditions such as the temperature, pH, concentration of metal ion, stoichiometric proportion of the reaction mixture and incubation time based on their optical properties and SPR effect in UV-visible spectroscopy. The role of hydroxyl and carbonyl groups in functionalizing the metal ions with ChR was confirmed with Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis. It was also substantiated that the oxygen group from ChR donates electrons to metal ion and results in complexation; ionic Ag+ and Au3+ were reduced to Ag0 and Au0 nano-forms. The physiochemical state of obtained NPs was characterized through different exclusive instrumentation, which shows the presence of highly-stable, spherical, crystalline ChR–AgNPs and ChR–AuNPs with an average size of 14 ± 6 nm and 6 ± 2 nm respectively. In vitro anticancer results revealed that the formulated metallic NPs exhibit enhanced cytotoxicity over ChR in the treatment of two different breast carcinoma cell lines (MDA-MB-231 and MDA-MB-468). Furthermore, it was evident that the NPs cause cell death via the induction of apoptosis. A hemolysis assay with human erythrocytes demonstrates good blood biocompatibility of the NPs. Thus, the ChR functionalized metal NPs can be potentially employed as a combinational drug-nano platform for breast cancer therapy.

Entropy in good manufacturing system: Tool for quality assurance

It has been customary to implement Good Manufacturing Practices (GMP) in pharmaceutical organizations as a systematic and comprehensive quality approach and sometimes by regulatory enforcement. In this scenario, determination of the obvious entropy/disorder arising during the implementation has not been taken care of yet. Therefore, this paper gives the basis for applying query and visual perception of GMP system driven visualization approach, particularly the Laplace equation, to the determination of disorder and deviation pattern inside the GMP system applied in the organization. In this study, a three-dimensional mesh approached with raw and intermediate input handled under GMP parameter is considered to produce high quality products with minimum entropy (variation distribution) by adding the analogy wise different GMP parameters and process variables with Gauss Seidel iteration and thus producing visual picture of the entire system. The approximation involved in applying the equations to the GMP compliant aseptic region was analyzed. Using numerical technique and computer program, the Gauss Seidel iteration equations have been solved with appropriate GMP parameter and process variable. The result indicates that deviations vary over the GMP compliant system and that the process entropy affects the totality of disorderness. Experiments with model of GMP compliant reproductive medicine laboratory confirm that the new method provides optimal manufacturing maintaining GMP and high product quality through the visual representation of the entire system and activity to bring into notice the deviations.

An approach to noninvasive delivery, biodistribution, and fertility control potential evaluation of the Cuproferrogel iron oxide-copper-styrene maleic anhydride-dimethyl sulphoxide in the female

Under guidance of an external pulsed magnetic field the Cuproferrogel iron oxide-copper-styrene maleic anhydride-dimethyl sulphoxide delivered into the rat/rabbit oviduct resulted in oocytes with granulated cytoplasm, zona enlargement, membrane disintegration, and finally loss of viability in 72 hours. Also, the percentage biodistribution of magnetic and electrically conductive particles observed under safe level advocates the use of Cuproferrogel as a potential female fertility control molecule.

Probing suitable therapeutic nanoparticles for controlled drug delivery and diagnostic reproductive health biomarker development.

Nanomaterial mediated drug delivery represents a highly promising technique while its selectivity for reproductive healthcare application still remains a challenge. Since the delicate structure and functional role of reproductive tissue and gametes require the use of biocompatible nanomedicine/devices that do not affect fertility or the development of resulting offspring, this paper reports an intercomparative study of human spermatozoa interaction with three different nanoparticles (NPs) namely; iron oxide (Fe3O4), multiwalled carbon nanotubes (MWCNT) and graphene platelet nanopowder (GPN) to probe their suitability for drug delivery carrier and biomarker development purposes. ATR-FTIR results revealed that the sperm cell interaction with GPN had maximum amide I absorption for cell proteins and CO stretching of the peptide backbone at the band around 1657 cm(-1) followed by iron oxide NPs whereas MWCNT had no absorption. These results showed that GPN followed by iron oxide NPs got maximally entrapped by cell membrane protein with maximum disruption but MWCNT exhibited less entrapment but significantly higher internalization which was further validated by morphological analysis of these cell NP interaction by SEM, HRTEM and fluorescence microscopy. The uptake kinetics and penetration mechanism of NPs were examined with isothermal titration calorimetry (ITC). Interestingly, ITC results confirmed ATR-FTIR and morphological observations that the binding of GPN and Fe3O4 NPs with cell was exothermic and their bindings were favored by both negative enthalpy and positive entropy whereas in the case of MWCNT it was endothermic supported by unfavorable positive enthalpy and a favorable entropy change. Hence, it was evident that MWCNT had better internalization efficiency without disrupting the sperm lipid membrane compared to Fe3O4 and GPN NPs. Therefore, this work proposes CNT as promising means.

Potential targetability of multi-walled carbon nanotube loaded with silver nanoparticles photosynthesized from Ocimum tenuiflorum (tulsi extract) in fertility diagnosis

Abstract Nanocarrier mediated targeted delivery and biosensing in reproductive health care is a major exploratory domain. This work demonstrates the loading of silver nanoparticle (AgNP) inside the multiwalled carbon nanotube (MWCNT) and their targetability to the intracellular part of the sperm cell for its further application in biosensing based infertility diagnosis. Ocimum tenuiflorum (tulsi extract) mediated photosynthesized AgNP exhibited spherical shape, 5–40 nm size and surface plasmonic resonance at 430 nm. After loading of freshly prepared AgNP into emulsified MWCNT, the loading was confirmed with spectroscopic and microscopic methods. FTIR analysis displayed significant shifting at 3450 cm−1 (–OH stretching) and 1615 cm−1 (CNT back bone) which validated the binding of AgNP with MWCNT and interestingly heat flow analysis revealed that Ag loaded MWCNT has greater stability than AgNP. Moreover, AFM based surface profile height analysis clearly showed the loading of AgNP inside MWCNT as surface height of MWCNT increased from 22 to 32 nm, which in turn confirmed the encapsulation of 10 nm size of AgNP inside the tube. Furthermore, surface enhanced Raman spectroscopy (SERS) confirmed the homogeneous loading as there were no changes in D/G ratio. SERS analysis for the interaction of AgNP loaded MWCNT with freshly collected healthy, motile human spermatozoa showed a significant Raman shift at 800–780 cm−1 (NH2+ twist) and 1050–1060 cm−1 (vas PO3−) for change in DNA packaging process and its stabilizing protein polyamine respectively. Finally, DNA fragmentation and morphological examination confirmed the binding and targetability of AgNP to the sperm nucleus. Improved targeting efficiency and biosenssing ability make AgNP-MWCNT composite suitable in fertility diagnosis.