Novel Drug Delivery Approaches for the Localized Treatment of Cervical Cancer.

Cervical cancer (CC) is the fourth leading cancer type in females globally. Being an ailment of the birth canal, primitive treatment strategies, including surgery, radiation, or laser therapy, bring along the risk of infertility, neonate mortality, premature parturition, etc. Systemic chemotherapy led to systemic toxicity. Therefore, delivering a smaller cargo of therapeutics to the local site is more beneficial in terms of efficacy as well as safety. Due to the regeneration of cervicovaginal mucus, conventional dosage forms come with the limitations of leaking, the requirement of repeated administration, and compromised vaginal retention. Therefore, these days novel strategies are being investigated with the ability to combat the limitations of conventional formulations. Novel carriers can be engineered to manipulate bioadhesive properties and sustained release patterns can be obtained thus leading to the maintenance of actives at therapeutic level locally for a longer period. Other than the purpose of CC treatment, these delivery systems also have been designed as postoperative care where a certain dose of antitumor agent will be maintained in the cervix postsurgical removal of the tumor. Herein, the most explored localized delivery systems for the treatment of CC, namely, nanofibers, nanoparticles, in situ gel, liposome, and hydrogel, have been discussed in detail. These carriers have exceptional properties that have been further modified with the aid of a wide range of polymers in order to serve the required purpose of therapeutic effect, safety, and stability. Further, the safety of these delivery systems toward vital organs has also been discussed.

Chemometric profiling and anti-arthritic activity of aerial parts of Glinus oppositifolius (L.) Aug. DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Glinus oppositifolius (L.) Aug. DC. belongs to the family Molluginaceae, an annual prostrate herb traditionally used to treat inflammations, arthritis, malarial, wounds, fevers, diarrhoea, cancer, stomach discomfort, jaundice, and intestinal parasites. However, the anti-arthritic activity of the aerial part has still not been reported. AIM OF THE STUDY: To investigate the antioxidant and anti-arthritic activity of G. oppositifolius in Complete Freund's Adjuvant (CFA) induced rats. MATERIALS AND METHODS: The dried aerial parts of this plant material were defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The in vitro anti-arthritic activity of methanolic extract of G. oppositifolius (MEGO) was evaluated in protein denaturation, membrane stabilization, and inhibition of proteinase assay at 25, 50, 100, 200, and 400 µg/ml concentrations. Female Wistar rats were immunized sub-dermally into the right hind paw with 0.1 ml of CFA. Rats were administered with MEGO at doses of 200 and 400 mg/kg once daily for fourteen days after arthritis induction. Assessment of arthritis was performed by measuring paw diameter, arthritic index, arthritic score, body weight, organ weight, and hematological and biochemical parameters, followed by the analysis of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1-beta (IL-1ß), cyclooxygenase-2 (COX-2), interleukin 13 (IL-13) and interleukin 10 (IL-10) and histopathological study. In vivo antioxidant effect was investigated in enzymatic assays. The presence of phytoconstituents was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. In silico molecular docking study of the compounds was carried out against COX-2, IL-1ß, IL-6, and TNF-α using AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer software. RESULTS: MEGO's in vitro anti-arthritic activity showed dose-dependent inhibition of protein denaturation, membrane stabilization, and proteinase inhibition, followed by significant in vivo anti-arthritic activity. The rats treated with MEGO showed tremendous potential in managing arthritis-like symptoms by restoring hematological, biochemical, and histological changes in CFA-induced rats. MEGO (200 and 400 mg/kg) showed a significant alleviation in the levels of hyper expressed inflammatory mediators (TNF-α, IL-1ß, and IL-6) and oxidative stress (SOD, CAT, GSH, and LPO) in CFA-induced rats. Spergulagenin-A as identified by LC-MS analysis, exhibited the highest binding affinity against COX-2 (-8.6), IL-1ß (7.2 kcal/mol), IL-6 (-7.4 kcal/mol), and TNF-α (-6.5 kcal/mol). CONCLUSIONS: Provided with the comprehensive investigation, methanolic extract of G. oppositifolius against arthritic-like condition is a proof of concept that revalidates its ethnic claim. The presence of Spergulagenin-A might be responsible for the anti-arthritic activity.

Gelatin carrageenan sericin hydrogel composites improves cell viability of cryopreserved SaOS-2 cells.

Cryopreservation and the low revival rate of cryopreserved cells remains a major challenge in cell based bone regeneration therapies. In our current study we aimed to develop a sericin based hydrogel composite incorporating various drugs and growth factors to enhance cell attachment, cryopreservation to increase the cellular viability upon revival. Sericin, gelatin and carrageenan blended hydrogel composites were prepared and explored for their physicochemical properties. The hydrogels prepared were porous and showed higher biocompatibility. Further, silver nanoparticles, alendronate and insulin like growth factor (IGF-1) were incorporated into the hybrid hydrogels individually and checked for sustained drug release profile. IGF-1 incorporated hydrogels composites showed better osteogenic cell attachment, proliferation and cell revival upon cryopreservation. The clonogenic potential of seeded cells upon 30 days of cryopreservation was also evaluated which was 55% in IGF-1 incorporated scaffold cells. A flow cytometry based staining protocol using Annexin V was developed which showed a live cell population up to 80% even after 30 days of crypreservation. These results validate the potential of our formulated hydrogels as cell based systems aimed for increasing cell survival upon cryopreservation and thus has a great potential for bone repair and regeneration.

Amino acid profiling and antimicrobial activity of Cucurbita moschata and Lagenaria siceraria seed protein hydrolysates.

Cucurbita moschata and Lagenaria siceraria seed proteins were extracted and hydrolysed with trypsin in order to recover antibacterial peptides. Amino acid content and molecular weight distribution were estimated to justify their co-relationship with antimicrobial activity. Antimicrobial activities of C. moschata and L. siceraria seed protein hydrolysates against three Gram-negative bacteria and two Gram-positive bacteria were evaluated. Seed protein hydrolysates of both of these plants have significantly higher activity against Acinetobacter baumannii (p < 0.05). The lethal concentration (LC50) values of L. siceraria hydrolysates (LSH) and C. moschata hydrolysates (CMH) were 70 ± 6.2 and 135.6 ± 4.5 µg/mL in viable count method and 73.2 ± 2.9 and 122.9 ± 3.2 µg/mL in turbidity method, respectively, against A. baumannii. Based on the above findings, seed protein hydrolysates of these plants may be considered as nutritional food and functional antimicrobial agents in food system.

Chemometric profile, antioxidant and tyrosinase inhibitory activity of Camel's foot creeper leaves (Bauhinia vahlii).

The present study is the first effort to a comprehensive evaluation of antityrosinase activity and chemometric analysis of Bauhinia vahlii. The experimental results revealed that the methanol extract of Bauhinia vahlii (BVM) possesses higher polyphenolic compounds and total antioxidant activity than those reported elsewhere for other more conventionally and geographically different varieties. The BVM contain saturated fatty acids such as hexadecanoic acid (10.15%), octadecanoic acid (1.97%), oleic acid (0.61%) and cis-vaccenic acid (2.43%) along with vitamin E (12.71%), α-amyrin (9.84%), methyl salicylate (2.39%) and ß-sitosterol (17.35%), which were mainly responsible for antioxidant as well as tyrosinase inhibitory activity. Tyrosinase inhibitory activity of this extract was comparable to that of Kojic acid. These findings suggested that the B. vahlii leaves could be exploited as potential source of natural antioxidant and tyrosinase inhibitory agent, as well.

Amino acid composition, antioxidant and functional properties of protein hydrolysates from Cucurbitaceae seeds.

In this study, the effect of enzymatic hydrolysis of globulin fraction of C. moschata (CMH), C. lanatus (CLH) and L. siceraria (LSH) on antioxidant capacity, functional properties, structural and micro-structural properties, as well as amino acid compositions were evaluated. All the hydrolysates exhibited significant antioxidant properties. The essential amino acids content in LSH (92.7 mg/g) was higher than CMH (79.9 mg/g) and CLH (70.5 mg/g). Water absorption capacity (5 g/g), heat stability (89%), emulsifying activity index (98.3 m2/g) and emulsifying stability index (45.1 min) were statistically more significant for LSH as compared to CMH and CLH. In addition, LSH had significantly higher FS and FC at pH 3-9. Among all hydrolysates, LSH showed highest solubility (87.3%) as compared to other hydrolysates. The results suggested that enzymatic hydrolysis improve the antioxidant and functional properties. Thus, the globulin hydrolysates might be served as an innovative source with promising nutritive values, good antioxidant and functional properties. Moreover, these could be used in food and pharmaceutical industries for the development of novel functional foods.