Muhammad Sarfraz

Biological control of the diamondback moth, Plutella xylostella: A review

Abstract The diamondback moth (DBM), Plutella xylostella (L.) (Lepidoptera: Plutellidae), is one of the most destructive cosmopolitan insect pests of brassicaceous crops. It was the first crop insect reported to be resistant to DDT and now, in many crucifer producing regions, it has shown significant resistance to almost every synthetic insecticide applied in the field. In certain parts of the world, economical production of crucifers has become almost impossible due to insecticidal control failures. Consequently, increased efforts worldwide have been undertaken to develop integrated pest management (IPM) programs, principally based on manipulation of its natural enemies. Although over 130 parasitoid species are known to attack various life stages of DBM, most control worldwide is achieved by relatively few hymenopteran species belonging to the ichneumonid genera Diadegma and Diadromus, the braconid genera Microplitis and Cotesia, and the eulophid genus Oomyzus. DBM populations native to different regions have genetic and biological differences, and specific parasitoid strains may be associated with the specific DBM strains. Therefore, accurate identification based on genetic studies of both host and parasitoid is of crucial importance to attaining successful control of DBM through inoculative or inundative releases. Although parasitoids of DBM larvae and pupae are currently its principal regulators, bacteria-derived products (e.g., crystal toxins from Bacillus thuringiensis) and myco-insecticides principally based on Zoophthora radicans and Beauveria bassiana are increasingly being applied or investigated for biological control. Viruses, nematodes and microsporidia also have potential as biopesticides for DBM. When an insect pest is exposed to more than one mortality factor, there is the possibility of interactions that can enhance, limit, or limit and enhance the various aspects of effectiveness of a particular control tactic. This paper reviews the effectiveness of various parasitoids and entomopathogens against DBM, interactions among them, and their possible integration into modern IPM programs.

Liposomal drug delivery: a versatile platform for challenging clinical applications.

Liposomes are lipid based vesicular systems that offer novel platform for versatile drug delivery to target cell. Liposomes were first reported by Bangham and his co-workers in 1964 (1). Since then, liposomes have undergone extensive research with the prime aim to optimize encapsulation, stability, circulation time and target specific drug delivery. Manipulation of a liposomes lipid bilayer and surface decoration with selective ligands has transformed conventional liposomes into adaptable and multifunctional liposomes. Development of liposomes with target specificity provide the prospect of safe and effective therapy for challenging clinical applications. Bioresponsive liposomes offer the opportunity to release payload in response to tissue specific microenvironment. Incorporation of novel natural and synthetic materials has extended their application from stable formulations to controlled release targeted drug delivery systems. Integration and optimization of multiple features into one system revolutionized research in the field of cancer, gene therapy, immunotherapy and infectious diseases. After 50 years since the first publication, this review is aimed to highlight next generation of liposomes, their preparation methods and progress in clinical applications.

Physicochemical, in vitro and in vivo evaluation of flurbiprofen microemulsion

Flurbiprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of flurbiprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, microemulsions have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The purpose of this study was to formulate and characterize gel based microemulsions, for topical delivery of flurbiprofen. Different gel bases, containing microemulsion and hydro-alcoholic solution of flurbiprofen, were developed and compared. In vitro study showed that gels containing microemulsion had a higher permeation rate than those containing hydro-alcoholic solutions. Additionally, formulation of Carbopol-I (microemulsion) showed higher percent of inhibition of inflammation than others bases. Further, skin irritation study demonstrated that Carbopol-I was none irritating. Flurbiprofen microemulsion incorporated on Carbopol-I showed physicochemical, in vitro and in vivo characteristics suitable for the development of alternative transdermal delivery formulation.

Immune response to antituberculosis drug-loaded gelatin and polyisobutyl-cyanoacrylate nanoparticles in macrophages

AIM Secondary toxicity of nanoparticles (NPs) in macrophages is a well-known phenomenon. The aim of the study was to investigate the immuneresponse of macrophages after NP treatment. METHODS & RESULTS Antituberculosis drugs moxifloxacin and rifampicin were loaded into gelatin and polyisobutyl-cyanoacrylate NPs. The NPs were physicochemical characterized. Cellular immuneresponses and cellular viability were determined. The drug release kinetics vary depending on the type of NP, size and loading capacity. IC50 values of polyisobutyl-cyanoacrylate NPs were lower than for gelatin NPs. NPs treatment induced higher release of Th1 type cytokines compared with free drug. CONCLUSION NPs together with chemotherapeutic drugs might be able to trigger an immune response in macrophages. The combined effect might be able to overcome mycobacteria infections.

Liposomal co-delivered oleanolic acid attenuates doxorubicin-induced multi-organ toxicity in hepatocellular carcinoma

Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC). OA attenuated the cardiotoxicity induced by doxorubicin without compromising its anticancer activity. Apoptosis assays revealed that co-delivery of DOX and OA produced a synergistic anticancer effect. However, the drugs had antagonistic effects on cardiomyocytes. Female BALB/c nude mice treated with OA- and DOX-loaded liposomes (ODLs) exhibited reduced tumor growth, stable body weight, and stable organ indices. Reduced 20-HETE production suggested ODLs had limited cardiotoxicity. No changes in biochemical or histopathological markers were observed in mice treated with ODLs. Tailored co-delivery of OA and DOX may thus be an effective therapeutic strategy for treating HCC.

Inflammation Caused by Nanosized Delivery Systems: Is There a Benefit?

Secondary macrophage cytotoxicity induced by nanoparticles was described before. The study aim was to investigate the role of secondary cytotoxic effect in a macrophage-lung cancer coculture model after nanoparticle treatment in the presence and absence of anti-inflammatory drugs. An in vitro coculture model composed of confluent alveolar macrophage MH-S and A-549 lung cancer cells separated by a 0.4 μm porous membrane was used in the study. Macrophages were treated with two sizes of gelatin nanoparticles and two sizes of poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles, with and without doxorubicin as a chemotherapeutic drug. The treatment effect with and without the presence of anti-inflammatory drug was studied using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The model drugs were ibuprofen, celecoxib, prednisolone, dexamethasone, and methotrexate. Different nanoparticles in different sizes were synthesized with a range of physicochemical characteristics. Doxorubicin loaded nanoparticles were prepared with an entrapment efficiency of 82-83% for PIBCA and 39-42% for gelatin. Nanoparticle treatment of macrophages showed a secondary cytotoxic effect on A-549 cancer cells at 24 and 36 h, with a drop in cell viability of 40-62%. However, this effect was significantly reduced to 10-48% if the macrophages were exposed to anti-inflammatory drugs. When ibuprofen and celecoxib were used the cell viability rebounded between 24 and 36 h. For prednisolone, dexamethasone, and methotrexate the cell viability dropped further between 24 and 36 h. Macrophages exposed to nanoparticles show secondary cytotoxicity, which has a significant antitumor effect in the microclimate of the coculture model. The beneficial nanoparticle treatment effect was significantly reduced if nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, or methotrexate was given at the same time. The data suggest that anti-inflammatory treatments can decrease the carrier-induced macrophage cytotoxicity and its antitumor effectiveness with chemotherapy.

Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies

Oleanolic acid (OA), which is a natural pentacyclic terpenoid, has been identified for hepato-protective, nephron-protective and cardio-tonic properties. In contrast, doxorubicin (DOX) is a famous anti-cancer drug but its efficacy is a question mark because of its known cardio-toxicity. We developed a combined nanoliposomal formulation of DOX with OA, as adjuvant, to overwhelm toxic effects of DOX without compromising anticancer activity. The entrapment efficiency and the particle size were brought in limit by the reengineered ethanolic injection method (REIM), without further extrusion. The developed formulations were stable over the study period of two months. A modified HPLC method was employed for the analysis of OA (drug retention time, Tr = 12 ± 1 min). The recovery of OA against spiked plasma samples was more than 90%. MTT assay showed anti-apoptotic synergism against HepG2 cells at non-fixed ratio (combination index, CI < 1). A sustained in vivo drug release of experimental drugs was depicted over 24 h. Histopathological examination and laboratory findings indicated no visible sign of toxicity in the treated mice group against combined delivery. Hence, this combined nanoliposomal formulation was tagged as a safer therapy for the DOX based cancer treatments.