Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy

Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (w/w) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.

Inhibition of oomycetes by the mixture of maleic acid and copper sulfate

After the discovery of the protective activity of Bordeaux mixture against plant disease caused by oomycetes, copper compounds have been used for over a century as a significant plant protection strategy. However, application of excessive copper can cause adverse effects through long-term heavy metal accumulation in soils. Therefore, it is necessary to develop new strategies to reduce or replace copper in pesticides based on organic and low-input farming systems. Organic acids are eco-friendly in nature. In this study, we tested the antifungal and anti-oomycete activity of maleic acid (MA) and copper sulfate (CS) against thirteen plant pathogens. Treatment of MA and CS mixture showed strong anti-oomycetes activity against Phytophthora cambivora, P. capsici and P. cinamomi. Moreover, the concentration of CS in the activated mixture of MA and CS was lower than that in the activated CS only, and the mixture showed synergy or partial synergy effects on the anti-oomycete activity. Application of a wettable powder formulation of MA and CS mixture (MCS 30WP; 26.67 % MA and 3.33 % CS) exhibited excellent protective activities in pot experiments with control values of 73 % Phytophthora blight on red pepper, 91 % damping-off on cucumber, and 84 % Pythium blight on creeping bentgrass, which are similar to those of the CS wettable powder formulation (6.67 % CS) containing two times the CS content in MCS 30WP. These observations suggest that the synergistic effect of the MA and CS combination is a sustainable alternative for effective management the destructive oomycete diseases.

AUG-3387, a Human-Derived Monoclonal Antibody Neutralizes SARS-CoV-2 Variants and Reduces Viral Load from Therapeutic Treatment of Hamsters In Vivo

Infections from the SARS-CoV-2 virus have killed over 4.6 million people since it began spreading through human populations in late 2019. In order to develop a therapeutic or prophylactic antibody to help mitigate the effects of the pandemic, a human monoclonal antibody (mAb) that binds to the SARS-CoV-2 spike protein was isolated from a convalescent patient following recovery from COVID-19 disease. This mAb, designated AUG-3387, demonstrates a high affinity for the spike protein of the original viral strains and all variants tested to date. In vitro pseudovirus neutralization and SARS-CoV-2 neutralization activity has been demonstrated in vitro. In addition, a dry powder formulation has been prepared using a Thin Film Freezing (TFF) process that exhibited a fine particle fraction (FPF) of 50.95 ± 7.69% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 3.74 ± 0.73 μm and 2.73 ± 0.20, respectively. The dry powder is suitable for delivery directly to the lungs of infected patients using a dry powder inhaler device. Importantly, AUG-3387, administered as a liquid by intraperitoneal injection or the dry powder formulation delivered intratracheally into Syrian hamsters 24 hours after intranasal SARS-CoV-2 infection, demonstrated a dose-dependent reduction in the lung viral load of the virus. These data suggest that AUG-3387 formulated as a dry powder demonstrates potential to treat COVID-19.

Formulation and Evaluation of Poly Herbal Liqui-Solid Compact for its Anti-Inflammatory Effect

Liquisolid approach is a potential method due to the ease in the production process, low cost, and manufacturing process because of their strong flow and compaction properties. The study's main goal is to create a liquisolid powder formulation from the polyherbal extract and evaluate its anti-inflammatory activity. Hibiscus cannabinus, Murraya koenigii, and Tabernaemontana divaricate are used to formulating polyherbal Liquisolid powder formulation to assess their anti-inflammatory action. The formulation is tested for its stability studies and anti-inflammatory activity, both in-vitro and in-vivo. The polyherbal liquisolid powder formulation (F5) has a minimum strength of 1kg/cm 2, while F2 & F6 strength was 4 kg/cm2; FTIR studies showed no interactions between drug and excipients. To confirm the liquisolid powder formulation, further evaluations on friability, hardness, disintegration time, dissolution rate, and Differential scanning calorimetry and X-ray powder diffraction analysis were determined. The polyherbal extract's anti-inflammatory activities were evaluated using the paw edema and cotton pellet method, and the results are found to exhibit its inhibitory activity. The polyherbal extract of Liquisolid powder formulation was evaluated, and it showed a promising inhibitory activity to overcome the inflammation in the test species. Hence it can be used as an alternative therapy for curing inflammation.

Bio-efficacy of Plants based Formulations for the Management of Cowpea Aphid (Aphis craccivora Koch.)

Background: The cowpea (Vigna unguiculata) is damaged by various insect pests of which cowpea aphid (Aphis craccivora) causes heavy damage to the tender leaves of the plant and reduces its yield. Two plant based formulation (prepared in the Chemistry Laboratory) viz. Polygonum hydropiper floral parts and Tobacco (Nicotiana tabacum) leaf, were used for safe management. Methods: The studies were done during 2019-2020 in BCKV, Kalyani, West Bengal, India for controlling of cowpea aphid by using plant based formulation. For preparing wettable powder formulation from Polygonum hydropiper floral parts and tobacco leaf the different ingredients are required viz. china clay, silica gel, wetting agent, dispersing agent etc. Physico-chemical analysis was done for preparation of accurate Wettable Powder formulation. Result: Cowpea aphid causes damage the tender leaves of the plant. It was revealed that imidacloprid (Confidor 17.8 SL) @ 1.0 ml/3L was found the most effective treatment against aphids giving more than 80% control followed by tobacco leaf (50 WP) @ 8 g/L of water (more than 70% control), fipronil (Regent 5% SC) @ 2.5 ml/L of water and Polygonum floral parts (50 WP) @ 8 g/L of water (more than 65% control both). The quality parameters of WP (50%) formulation was satisfactory as per the FAO specifications in terms of wet sieved test, wettability, foaming and suspensibility performed on the 0-day and also after 15th day at room temperature, at 65°C and at freezing temperature conditions.

Preparation of Poly-Lactic-Co-Glycolic Acid Nanoparticles in a Dry Powder Formulation for Pulmonary Antigen Delivery

One of the key requirements for successful vaccination via the mucosa is particulate antigen uptake. Poly-lactic-co-glycolic acid (PLGA) particles were chosen as well-known model carriers and ovalbumin (OVA) as the model antigen. Aiming at application to the respiratory tract, which allows direct interaction of the formulation with the mucosal immune system, this work focuses on the feasibility of delivering the antigen in a nanoparticulate carrier within a powder capable of pulmonary delivery. Further requirements were adequate antigen encapsulation in order to use the characteristics of the particulate carrier for (tunable) antigen release, and capability of the production process for industrialisation (realisation in industry). For an effective particulate antigen uptake, nanoparticles with a size of around 300 nm were prepared. For this, two production methods for nanoparticles, solvent change precipitation and the double emulsion method, were evaluated with respect to antigen incorporation, transfer to a dry powder formulation, redispersion and antigen release characteristics. A spray drying step was included in the production procedure in order to obtain a respirable powder with an aerodynamic particle size of between 0.5 and 5 μm. The dried products were characterised for particle size, dispersibility and aerodynamic behaviour, as well as for immune response and cytotoxicity in cell culture models. It could be shown that the double emulsion method is suitable to prepare nanoparticles (270 nm) and to incorporate the antigen. By modifying the production method to prepare porous particles, it was possible to obtain an acceptable antigen release while maintaining an antigen load of about 10%. By the choice of polyvinyl alcohol as a stabiliser, nanoparticles could be dried and redispersed without further excipients and the production steps were capable of realisation in industry. Aerodynamic characteristics were good with a mass median aerodynamic diameter of 3.3 µm upon dispersion from a capsule-based inhaler.