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Purpose: Amikacin, a water-soluble aminoglycoside antibiotic used to treat gram-negative bacillary infections, is a Biopharmaceutics Classification System class III drug having poor permeability and short half-life. It is given parenterally, which limits its use in patients warranting "at-home care." An oral drug delivery of amikacin is, therefore, imminent. Aim: This work focused on establishing poly d, l-lactide-co-glycolide (PLGA)-based nanoparticles of amikacin with consolidated pharmaceutical attributes capable of circumventing gastrointestinal tract membrane barriers and promoting oral administration of the drug. The partied attributes are suggestive of enhanced uptake of the drug via Peyer's patches overlaying small intestine and support successful oral delivery. Materials and Methods: To have a robust delivery system, a statistical Box–Behnken experimental design was used and formulation parameters such as homogenization time, probe sonication time, and drug/polymer ratio of amikacin-loaded PLGA nanoparticles (A-NPs) for obtaining monodispersed nanoparticles of adequate size and high drug loading were optimized. Results: The model suggested to use the optimum homogenization time, probe sonication time, and drug/polymer ratio as 30s, 120s, and 1:10, respectively. Under these formulation conditions, the particle size was found to be 260.3nm and the drug loading was 3.645%. Conclusion: Biodegradable PLGA nanoparticulate systems with high payload, optimum size, and low polydispersity index will ensure successful uptake and ultimately leading to better bioavailability. Hence, under the aforementioned optimized conditions, the A-NPs prepared had particle size of 260.3nm, which is appreciable for its permeability across small intestine, and drug loading of 3.645%. [ABSTRACT FROM AUTHOR]

Context: Medical management of heavy metal toxicity including radioactive ones is the cause of concern because of their increased use in energy production, healthcare and mining. As inhalation is one of the primary routes for internalization, a formulation is needed to trap metal(s) at the portal of entry itself. Objective: Objective was to formulate and characterize a nanonized dry powder inhaler (DPI) formulation of alendronate sodium as potential inhalable antidote for chelating metal toxicants. Methods. In vitro binding studies of alendronate with respect to seven non-radioactive heavy metals were carried out using UV-spectroscopy and HPLC. Nanonizing of alendronate particles was achieved by antisolvent precipitation using Pluronic-F68 as stabilizer. Characterization was done with the help of SEM, TEM FT-IR, XRD, DSC, NMR spectroscopy and PSD studies. In vitro and in vivo pulmonary deposition studies were carried out using gamma scintigraphy, followed by a limited pharmacokinetic study in humans. Results. In vitro binding studies confirmed the chelating action of alendronate. Anderson cascade impaction showed that nano-alendronate exhibited significantly higher respirable fraction (58.25 ± 1.32%) compared to the micronized form (28.7 ± 0.59%). Scintigraphy results showed significant increase in the alveolar deposition of drug post-nanonizing. Conclusion: Results strongly indicate the role of nano-alendronate DPI as potential inhalable antidote for neutralizing heavy metal toxicity, including radio-metal contamination. [ABSTRACT FROM AUTHOR]

Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89 ± 2.13%) with vesicle size of 144 ± 3.47 nm (polydispersity index [PDI] == 0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2 ± 0.015% drug was released in 24 h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 µg/mL in plasma) was also maintained for at least 8 h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir. [ABSTRACT FROM AUTHOR]