Polymeric Immunonanoparticles Mediated Cancer Therapy: Versatile Nanocarriers for Cell-Specific Cargo Delivery.

The major drawback with conventional therapeutic approaches for cancer therapy is decreased efficacy and redundant therapy associated toxicity and side effects causing increased patient discomfort. With the aim of minimizing these limitations, a vast amount of attention has been given to targeted nanocarrier-based drug delivery systems that possess a several-fold advantage over conventional therapy. Increased research in targeted nanoparticulate systems has led to the development of immunonanoparticles with enhanced efficacy and targeting efficiency along with decreased drug-resistant cancer- and dose-related toxicity. These immunonanoparticle- based therapies, which can be extended to immunotherapy, have gained wide attention, but few formulations will be approved by regulatory agencies in the near future. This review details the various immunonanoparticle systems explored in cancer therapy, with particular emphasis on polymeric nanoparticles. This review describes the mechanisms of immunotherapy and the pathways for targeting dendritic cells for immunotherapy. It also focuses on present status of clinical trials of immunonanoparticles and related patents, as well as various FDA-approved monoclonal antibodies (mAbs) for immunotherapy. Toxicity issues related to immunonanoparticles along with regulatory guidelines for these therapeutic nanoparticles are also discussed.

Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L.) Leaves.

In the present study, we evaluated anti-Parkinson's activity of petroleum ether extract of Ficus religiosa (PEFRE) leaves in haloperidol and 6 hydroxydopamine (6-OHDA) induced experimental animal models. In this study, effects of Ficus religiosa (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters like catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters (MDA, CAT, SOD, and GSH) in rats. The experiment was designed by giving haloperidol to induce catalepsy and 6-OHDA to induce Parkinson's disease-like symptoms. The increased cataleptic scores (induced by haloperidol) were significantly (p < 0.001) found to be reduced, with the PEFRE at a dose of 200 and 400 mg/kg (p.o.). 6-OHDA significantly induced motor dysfunction (muscle rigidity and hypolocomotion). 6-OHDA administration showed significant increase in lipid peroxidation level and depleted superoxide dismutase, catalase, and reduced glutathione level. Daily administration of PEFRE (400 mg/kg) significantly improved motor performance and also significantly attenuated oxidative damage. Thus, the study proved that Ficus religiosa treatment significantly attenuated the motor defects and also protected the brain from oxidative stress.

Clerodendrum serratum (L.) Moon. - a review on traditional uses, phytochemistry and pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Clerodendrum serratum (L.) Moon. (Verbenaceae) is an important medicinal plant growing in the tropical and warm temperate regions like Africa, Southern Asia; Malaysia and distributed throughout in forests of India and Sri Lanka. It is traditionally valued and reported for treating pain, inflammation, rheumatism, respiratory disorders, fever and malarial fever in India with a long history. To provide a comprehensive overview of the traditional and ethno medicinal uses, phytochemistry and biological activities of C. serratum with clinical and toxicity data and possibly make recommendations for further research. MATERIALS AND METHODS: All relevant worldwide accepted databases were searched for the terms "Clerodendrum", "Clerodendrum serratum", "Bharangi" and "Cheruthekku" along with the other literature from Indian classical texts and pharmacopoeias. There was no specific timeline set for the search. The accessible literatures available on C. serratum were collected via electronic search using Pubmed, Scopus, Science Direct and traditional books reports on ethnopharmacology and traditional medicines. RESULTS: C. serratum has played an important role in Indian system of medicine. In addition to the common local use in respiratory diseases, other ethnomedicinal uses include treatment of pain, inflammation, rheumatism and fever especially malarial fever. Scientific studies on extracts and formulations revealed anti-asthmatic, mast cell stabilization and anti-allergic effects of roots of C. serratum. Reported data on pharmacological activities also includes hepatoprotective, anti-oxidant, anti-inflammatory and anticancer potential of the drug. Saponins (terpenoids and steroids), flavonoids and phenolics isolated from roots have been the focus of phytochemical investigations as the biological activity has been ascribed to the saponins, which are known to possess anti-inflammatory and anti-cancer activity. Isolated bioactives from roots like icosahydropicenic acid and ursolic acid have been claimed to offer anti-allergic and hepatoprotective activity. CONCLUSIONS: Therapeutic potential of roots and leaves of C. serratum has been demonstrated in the conditions like asthma, allergy, fever, inflammation and liver disorders attributed to the presence of various flavonoids, phenolics and saponins present in the drug. Many ethnobotanical claims have been confirmed through modern in-vitro and in-vivo pharmacological studies of different extracts and isolates from plant; however, additional studies on the biomarkers are needed to establish mechanism of action and to validate the traditional use of this drug in clinical practices after proper safety assessment.

Exploration of statistical experimental design to improve entrapment efficiency of acyclovir in poly (d, l) lactide nanoparticles.

OBJECTIVE: In current exploration, systematic attempts have been made to improve the entrapment efficiency of a model hydrophilic drug substance, i.e. acyclovir, in poly (d, l) lactide (PLA) nanoparticles (NPs) using a modified nanoprecipitation technique. METHODS: Formulation parameters such as drug to polymer ratio, antisolvent selection, electrolyte (NaCl) addition, pH alteration and temperature were screened to improve the entrapment efficiency of acyclovir in PLA NPs. The temperature of the system (0-5 °C), phase volume ratio (1:2), stirring speed (2000 rpm), sonication time (5 min), etc. were kept constant during the preparation of NPs. Drug to polymer ratio and electrolyte addition emerged as critical formulation parameters affecting particle size as well as entrapment efficiency. Hence, in the present investigation a 3(2) full factorial design was used to investigate the combined influence of two factors, i.e. drug to polymer ratio (X1) and the amount of electrolyte, i.e. NaCl (X2) on particle size (Y1) and entrapment efficiency (Y2). The NPs were also evaluated for drug-excipient compatibility study by employing DSC and FT-IR analysis, whereas in vitro drug release studies were performed using dialysis bag technique in phosphate buffer pH 7.4. RESULTS: Statistically significant models were evolved to predict entrapment efficiency and particle size. The effect of factors X1, X2 and [Formula: see text] was found to be statistically significant in nature. Response variables, i.e. entrapment efficiency and particle size, were simultaneously optimized using desirability function using Design Expert software. This process allowed the selection of most suitable level of factors to achieve desired level of particle size and entrapment efficiency. The results of multiple linear regression analysis revealed that for obtaining desirable particle size (less than 250 nm) and entrapment efficiency (more than 17%), the NPs should be prepared using 1:3 drug to polymer ratio and 0.04 M NaCl. Acyclovir was found to be compatible with PLA as indicated by DSC and FT-IR studies. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The drug release from the optimized formulation exhibited biphasic pattern and the drug release kinetics was best explained by Weibull model. CONCLUSION: In conclusion, results of the present study demonstrated that PLA NPs with expected particle size and entrapment efficiency can be obtained by adopting the concept of quality by design.

Development and characterization of glutathione-conjugated albumin nanoparticles for improved brain delivery of hydrophilic fluorescent marker.

The glutathione-conjugated bovine serum albumin (BSA) nanoparticles were constructed in the present exploration as a novel biodegradable carrier for brain-specific drug delivery with evaluation of its in vitro and in vivo delivery properties. BSA nanocarriers were activated and conjugated to the distal amine functions of the glutathione via carbodiimide chemistry using EDAC as a mediator. These nanoparticles were characterized for particle shape, average size, SPAN value, drug entrapment and in vitro drug release. Further, presence of glutathione on the surface of BSA nanoparticles was confirmed by Ellman's assay, which has suggested that approximately 750 units of glutathione were conjugated per BSA nanoparticle. To evaluate the brain delivery properties of the glutathione-conjugated BSA nanoparticles fluorescein sodium was used as a model hydrophilic compound. Permeability and neuronal uptake properties of developed formulations were evaluated against the MDCK-MDR1 endothelial and neuro-glial cells, respectively. The permeability of glutathione-conjugated BSA nanoparticles across the monolayer of MDCK-MDR1 endothelial tight junction was shown significantly higher than that of unconjugated nanoparticles and fluorescein sodium solution. Similarly, glutathione-conjugated nanoparticles exhibited considerably higher uptake by neuro-glial cells which was inferred by high fluorescence intensity under microscope in comparison to unconjugated nanoparticles and fluorescein sodium solution. Following an intravenous administration, nearly three folds higher fluorescein sodium was carried to the rat brain by glutathione-conjugated nanoparticles as compared to unconjugated nanoparticles. The significant in vitro and in vivo results suggest that glutathione-conjugated BSA nanoparticles is a promising brain drug delivery system with low toxicity.