Lactoferrin-tethered betulinic acid nanoparticles promote rapid delivery and cell death in triple negative breast and laryngeal cancer cells.

Cancer management presents multifarious problems. Triple negative breast cancer (TNBC) is associated with inaccurate prognosis and limited chemotherapeutic options. Betulinic acid (BA) prevents angiogenesis and causes apoptosis of TNBC cells. NIH recommends BA for rapid access in cancer chemotherapy because of its cell-specific toxicity. BA however faces major challenges in therapeutic practices due to its limited solubility and cellular entree. We report lactoferrin (Lf) attached BA nanoparticles (Lf-BAnp) for rapid delivery in triple negative breast (MDA-MB-231) and laryngeal (HEp-2) cancer cell types. Lf association was confirmed by SDS-PAGE and FT-IR analysis. Average hydrodynamic size of Lf-BAnp was 147.7 ± 6.20 nm with ζ potential of -28.51 ± 3.52 mV. BA entrapment efficiency was 75.38 ± 2.70% and the release mechanism followed non-fickian pattern. Impact of Lf-BAnp on cell cycle and cytotoxicity of triple negative breast cancer and its metastatic site laryngeal cancer cell lines were analyzed. Lf-BAnp demonstrated strong anti-proliferative and cytotoxic effects, along with increased sub-G1 population and reduced number of cells in G1 and G2/M phases of the cell cycle, confirming reduced cell proliferation and significant cell death. Speedy intracellular entry of Lf-BAnp occurred within 30 min. Lf-BAnp design was explored for the first time as safer chemotherapeutic arsenals against complex TNBC conditions.

Semi-interpenetrating hydrogels from carboxymethyl guar gum and gelatin for ciprofloxacin sustained release.

The present work reports the synthesis of new generation semi-interpenetrating (s-IPN) hydrogels from carboxymethyl guar gum (CMGG) and gelatin with enhanced gel properties for suitable drug delivery applications. Hydrogels are three dimensional polymer networks which respond to water and ion interactions. Irreversible s-IPN hydrogels were prepared by CMGG interactions in gelatin and characterized in FT-IR, SEM and thermal studies. CMGG was synthesized by Hofmeister ion guided homogeneous phase reactions. The swelling kinetics of the newer s-IPN hydrogels followed Schott's pseudo second order model. Furthermore, the hydrogels were hemocompatible, non-cytotoxic and appropriate for applications in physiological environment. Model drug ciprofloxacin was loaded within the hydrogels and the drug release was found to be a combination of both diffusion and hydrogel degradation. New generation s-IPN biopolymer hydrogels of carboxymethyl guar gum and gelatin holds promise for its application as sustained drug delivery device or alternatively as hydrogel sorbents for bio-toxins and molecules of biomedical importance.

Highly monodispersed gold nanoparticles synthesis and inhibition of herpes simplex virus infections.

This work relates to quasi spherical gold nanoparticles synthesis and successful antiviral efficacy evaluations against Herpes simplex virus (HSV) infections. Ultrasound induced rapid reduction in gallic acid (GA) leads to highly monodispersed gold nanoparticles (GAunps). GAunps plasmonic peak was recorded at 531 nm with TEM size of 7.86 nm. X-ray diffraction and SAED pattern proved fcc crystalline structure. FTIR studies confirmed nanoparticles surface conjugation with gallic acid. The antiviral efficacy of GAunps was studied against HSV infections in Vero cells. GAunps were effective in dose-dependent manner with EC50 of 32.3 µM in HSV-1 and 38.6 µM in HSV-2. Further study revealed that GAunps prevented viral attachment and penetration into the Vero cells. The inhibition percentage varied with the nanoparticles exposure time in infected cells. Nanoparticles cytotoxicity (CC50 972.4 µM) in Vero cells was significantly lower than acyclovir (CC50 561.7 µM) indicating its safety. Bio-safe gold nanoparticles were proposed as a safer alternative in virus chemotherapy.

Lactoferrin-modified Betulinic Acid-loaded PLGA nanoparticles are strong anti-leishmanials.

Visceral Leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani, is a potentially fatal disease. The only orally bioavailable drug miltefosine is toxic and the effective liposomal Amphotericin B (AmBisome) is limited by its prohibitive cost and requirement for parenteral administration. Therefore, finding a new potential drug candidate and an alternative delivery system is imperative. We report that Betulinic acid (BA), a pentacyclic triterpenoid from Betula alba bark, was loaded onto uniformly spherical PLGA nanoparticles (BANPs; diameter 187.5 ±â€¯5.60 nm) coated with Lactoferrin (Lf-BANPs). The amastigotes count in macrophages was more effectively reduced by Lf-BANP than BA and BANP. Lf-BANPs reduced the pro-parasitic, anti-inflammatory cytokine IL-10, but increased nitric oxide (NO), production in L. donovani-infected macrophages indicating that Lf-BANP possesses a significant anti-leishmanial activity.

Andrographolide engineered gold nanoparticle to overcome drug resistant visceral leishmaniasis.

Visceral leishmaniasis (VL) is World Health Organization designated most serious leishmaniasis with an annual mortality rate of 50,000. Even after country specific eradication programs, the disease continues to multiply with added complexities like resistance development, drug hypersensitivity and associated infections. Newer therapeutic interventions are urgently warranted to control the spread. Present study aims to arrive at terpenoid andrographolide engineered gold nanoparticle (AGAunps) facile synthesis and its efficacy evaluations against wild and drug resistant VL strains for the first time. Molecular bio-organic conjugation of AGAunp was confirmed in FT-IR and EDAX studies. Nano-gold plasmon response was recorded at 543 nm and the average size in TEM was 14 nm. SAED pattern and XRD observations proved fcc crystalline structure of nano-gold. AGAunp recorded spherical geometry in AFM and TEM. PDI value of 0.137 revealed the monodisperse nature of the nano-scale population. AGAunp exhibited strong antileishmanicidal effect both against wild type (IC50 19 ± 1.7 µM) and sodium stibogluconate (IC50 55 ± 7.3 µM)/paromomycin (IC50 41 ± 6 µM) resistant strains. Complete macrophage uptake AGAunp's occured within two hours exposure. AGAunp macrophage cytotoxicity was significantly lower as compared to Amphotericin-B. Low toxic Andrographolide engineered gold nanoparticle emerged as promising alternatives in the control of wild and drug resistant VL.

In vitro susceptibilities of wild and drug resistant leishmania donovani amastigote stages to andrographolide nanoparticle: role of vitamin E derivative TPGS for nanoparticle efficacy.

Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50∶50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.