Sitagliptin (MK–0431) is a widely and commonly used oral hypoglycemic drug in the treatment of type 2 diabetes mellitus; patients typically take higher doses of this drug (50 mg, twice daily). One drawback is that only 38% of the drug is bound reversibly to plasma proteins and 79% is excreted in urine without being metabolized. To overcome this issue, there is a need for a better drug-delivery method to improve its efficacy in patients. It has been found that in existing formulations, the drug content is 72.5% ± 5% and the percentage yield is 84.9% ± 3%. In this study, sitagliptin nanoparticles (sizes ranging from 210 to 618 nm) were developed. The bioadhesion properties of the nanoparticles, as well as the swelling of the nanoparticles on the mucus membrane aided in sustained drug release. The pattern of drug release was in accordance with the Peppas model. Fourier-transform infrared (FTIR) spectroscopy demonstrated that there were no significant interactions between sitagliptin and chitosan. Differential scanning calorimetry (DSC) results showed an absence of drug peaks due to the fact that the drug was present in an amorphous state. Mucoadhesive nanoparticles were formulated using sitagliptin and were effective for about 12 hours in the gastrointestinal tract. When compared to conventional sitagliptin administration, use of a nanoparticle delivery system demonstrated greater benefits for use in oral delivery applications. This is the first time that a drug-delivery method based on the mucoadhesive properties of nanoparticles could prolong the drug-release time of sitagliptin.

Background: Chronic diseases such as diabetes, asthma, and heart disease are the leading causes of death in developing countries. Public health plays an important role in preventing such diseases to improve individuals' quality of life. Conventional dosage schemes used in public health to cure various diseases generally lead to undesirable side effects and renders the overall treatment ineffective. For example, a required concentration of drug cannot reach the lungs using conventional methods to cure asthma. Microspheres have emerged as a confirmed drug-delivery system to cure asthma. Method: In this paper, a salbutamol-loaded poly lactic acid-co-glycolic acid-polyethylene glycol (PLGA-PEG) microsphere (SPP)-based formulation was prepared using a Buchi B-90 nanospray drier. Face-centered central composite design (CCD) was applied to optimize the spray-drying process. Results: The drug content and product yield were found to be 72%±0.8% and 86%±0.4%, respectively; drug release (91.1%) peaked for up to 12 hrs in vitro. Microspheres obtained from the spray dryer were found to be shriveled. The experiments were carried out and verified using various groups of rabbits. In our study, the particle size (8.24 µm) was observed to be an essential parameter for drug delivery. The in vivo results indicated that the targeting efficacy and drug concentration in the lung was higher with the salbutamolloaded PLGA-PEG SPP formulation (1,410.1±10.11 µg/g, 15 mins), as compared to the conventional formulation (92±0.56 µg/g, 10 min). The final product was stable under 5°C±2°C , 25°C±2°C, and 40°C±2°C/75%±5% relative humidity. In addition, these co-polymers have a good safety profile, as determined by testing on human alveolar basal epithelium A549 cell lines. Conclusion: Our results prove that microspheres are an alternative drug-delivery system for lung-targeted asthma treatments used in public health.

Acute respiratory distress syndrome (ARDS), a catastrophic illness of multifactorial etiology, involves a rapid upsurge in inflammatory cytokines that leads to hypoxemic respiratory failure. Dexamethasone, a synthetic corticosteroid, mitigates the glucocorticoid-receptor-mediated inflammation and accelerates tissue homeostasis towards disease resolution. To minimize non-target organ side effects arising from frequent and chronic use of dexamethasone, we designed biodegradable, lung-targeted microspheres with sustained release profiles. Dexamethasone-loaded lipopolymeric microspheres of PLGA (Poly Lactic-co-Glycolic Acid) and DPPC (Dipalmitoylphosphatidylcholine) stabilized with vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate) were prepared by a single emulsion technique that had a mean diameter of 8.83 ± 0.32 μm and were spherical in shape as revealed from electron microscopy imaging. Pharmacokinetic and biodistribution patterns studied in the lungs, liver, and spleen of Wistar rats showed high selectivity and targeting efficiency for the lung tissue (re 13.98). As a proof-of-concept, in vivo efficacy of the microspheres was tested in the lipopolysaccharide-induced ARDS model in rats. Inflammation markers such as IL-1β, IL-6, and TNF-α, quantified in the bronchoalveolar lavage fluid indicated major improvement in rats treated with dexamethasone microspheres by intravenous route. Additionally, the microspheres substantially inhibited the protein infiltration, neutrophil accumulation and lipid peroxidation in the lungs of ARDS bearing rats, suggesting a reduction in oxidative stress. Histopathology showed decreased damage to the pulmonary tissue upon treatment with the dexamethasone-loaded microspheres. The multipronged formulation technology approach can thus serve as a potential treatment modality for reducing lung inflammation in ARDS. An improved therapeutic profile would help to reduce the dose, dosing frequency and, eventually, the toxicity.

Excessive architectural re-modeling of tissues in pulmonary fibrosis due to proliferation of myofibroblasts and deposition of extracellular matrix adversely affects the elasticity of the alveoli and lung function. Progressively destructive chronic inflammatory disease, therefore, necessitates safe and effective non-invasive airway delivery that can reach deep alveoli, restore the surfactant function and reduce oxidative stress. We designed an endogenous surfactant-based liposomal delivery system of naringin to be delivered as an aerosol that supports pulmonary mechanics for the management of pulmonary fibrosis. Phosphatidylcholine-based liposomes showed 91.5 ± 2.4% encapsulation of naringin, with a mean size of 171.4 ± 5.8 nm and zeta potential of −15.5 ± 1.3 mV. Liposomes with the unilamellar structure were found to be spherical and homogeneous in shape using electron microscope imaging. The formulation showed surface tension of 32.6 ± 0.96 mN/m and was able to maintain airway patency of 97 ± 2.5% for a 120 s test period ensuring the effective opening of lung capillaries and deep lung delivery. In vitro lung deposition utilizing Twin Stage Impinger showed 79 ± 1.5% deposition in lower airways, and Anderson Cascade Impactor deposition revealed a mass median aerodynamic diameter of 2.35 ± 1.02 μm for the aerosolized formulation. In vivo efficacy of the developed formulation was analyzed in bleomycin-induced lung fibrosis model in rats after administration by the inhalation route. Lactate dehydrogenase activity, total protein content, and inflammatory cell infiltration in broncho-alveolar lavage fluid were substantially reduced by liposomal naringin. Oxidative stress was minimized as observed from levels of antioxidant enzymes. Masson’s Trichrome staining of lung tissue revealed significant amelioration of histological changes and lesser deposition of collagen. Overall results indicated the therapeutic potential of the developed non-invasive aerosol formulation for the effective management of pulmonary fibrosis.

Context: Revised National Tuberculosis Control Program (RNTCP)-Directly Observed Treatment-Short course (DOTS) strategy to involve Community Pharmacist (CPs), was conceived and implemented in India, with the objective of improving accessibility of Tuberculosis free medicines. Though the RNTCP personnel in the study area had tried to create liaison with CPs; and to train them in DOTS provision roles, it was not successful as CPs were not forthcoming to be a part RNTCP-DOTS paradigm. Hence this study was ideated and executed to develop a liaison model between CP and RNTCP personnel, to support the delivery of DOTS treatment under RNTCP programme. This article discusses the liaison method followed by the researchers to integrate the CPs with RNTCP'S TB centres in Bangalore City. Aim: To establish liaison between community pharmacists and RNTCP personnel to strengthen Public Private Mix (PPM) Partnership for providing TB care role in Bengaluru City, India. Methodology: An educational interventional study involving CPs in Bengaluru City was conducted with the regulatory support from Drugs Control department, Karnataka.Awareness and Training was given on the basis of the RNTCP training module for Community Pharmacist. The change in the level of awareness on existence of PPM RNTCP strategy among community pharmacist; and the percentage of pharmacists showing interest for TB care role after the program was measured. Results and Discussion: Out of 125 CPs representations, 93 CPs enrolled them as Private DOTS providers immediately after programme. The change in the Level of Awareness on the existence of TB-DOTS provider role was found to be 100% in this study. This result clearly points to the fact that CPs needs to be sensitized. Conclusion: The policy level changes in the ease of enrolling CPs to be a DOTS provider under the aegis of drugs control department, needs to be revisited and rethought in RNTCP's national strategy for pharmacists.