Preparation, In Vitro Characterization, and In Vivo Pharmacokinetic Evaluation of Respirable Porous Microparticles Containing Rifampicin

Kundawala, Aliasgar J.; Patel, Viraat; Patel, Harsha V.; Choudhary, Dhaglaram

doi:10.3797/scipharm.1307-03

Cited by 14 publications

(3 citation statements)

References 22 publications

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“…The key role of these large particles is to avoid being phagocytized by alveolar macrophages because of their large geometric sizes. The deposited particles have an opportunity to release entrapped drugs to the surroundings. , Porous microspheres can be fabricated with the methods of solvent evaporation, spray drying, and supercritical fluid technology . However, these methods have disadvantages such as low encapsulation efficiency, difficulty in removing organic solvents, and of separation particles from the aqueous phase.…”

Section: Introductionmentioning

confidence: 99%

Drug-Loaded PLGA Electrospraying Porous Microspheres for the Local Therapy of Primary Lung Cancer via Pulmonary Delivery

2017

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Nonsmall-cell lung cancer is a severe disease with high morbidity and mortality. However, the systemic administration of anticancer drugs generally leads to serious toxicity and low anti-lung cancer efficiency because of very limited drug distribution in the lung. In our previous research, we have confirmed the high anti-lung cancer effect of inhalable oridonin microparticles in spite of their long and complicated preparation process. Here, we develop a novel, simple, and quick method for preparing inhalable oridonin-loaded poly(d,l-lactic-co-glycolic)acid (PLGA) porous microspheres using the electrospraying technique. The formulation and preparation processes were screened. The electrospraying porous microspheres (EPMs) were rough, porous, and suitable for pulmonary delivery. Most of the oridonin was released from the EPMs within 20 h based on drug diffusion and via PLGA erosion. The EPMs exhibited efficient lung deposition in vitro and in vivo because of their ideal aerodynamic diameters. Chemical carcinogens were used to prepare primary lung cancer rat models by direct pulmonary delivery. The EPMs showed high anti-lung cancer effect after pulmonary delivery according to CT images and pathology. Inhibition of angiogenesis and enhancement of lung cancer cell apoptosis could be the major anticancer mechanism. Electrospraying is an efficient method for the preparation of inhalable drug-loaded porous microspheres. The oridonin-loaded EPMs are promising dry powder inhalers for the local therapy of primary lung cancer.

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Section: Introductionmentioning

confidence: 99%

Drug-Loaded PLGA Electrospraying Porous Microspheres for the Local Therapy of Primary Lung Cancer via Pulmonary Delivery

2017

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“…Nevertheless, the study reported only mild changes in the lung histopathology, suggesting the absence of toxicity after the administration of rifampicin as an inhaled dry powder in rats. In bioavailability studies [ 48 , 73 ], low-dose rifampicin (5–20 mg/kg) was administered via the inhaled route to rats and guinea pigs, which demonstrated up to two-fold higher bioavailability of rifampicin compared to that from the oral route. In the guinea pig study, administration of 20 mg/kg rifampicin as porous particles via the inhaled route led to a relative bioavailability of 0.87 ± 0.33 compared to the intravenous rifampicin (10 mg/kg), while administration of the same via the oral route at 40 mg/kg dose achieved a relative bioavailability of only 0.61 ± 0.23 [ 48 ].…”

Section: Rifampicin: a Long-established Oral Anti-tb Drug With New Po...mentioning

confidence: 99%

A review of formulations and preclinical studies of inhaled rifampicin for its clinical translation

Khadka

Dummer

Hill

et al. 2022

Drug Deliv. and Transl. Res.

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Inhaled drug delivery is a promising approach to achieving high lung drug concentrations to facilitate efficient treatment of tuberculosis (TB) and to reduce the overall duration of treatment. Rifampicin is a good candidate for delivery via the pulmonary route. There have been no clinical studies yet at relevant inhaled doses despite the numerous studies investigating its formulation and preclinical properties for pulmonary delivery. This review discusses the clinical implications of pulmonary drug delivery in TB treatment, the drug delivery systems reported for pulmonary delivery of rifampicin, animal models, and the animal studies on inhaled rifampicin formulations, and the research gaps hindering the transition from preclinical development to clinical investigation. A review of reports in the literature suggested there have been minimal attempts to test inhaled formulations of rifampicin in laboratory animals at relevant high doses and there is a lack of appropriate studies in animal models. Published studies have reported testing only low doses (≤ 20 mg/kg) of rifampicin, and none of the studies has investigated the safety of inhaled rifampicin after repeated administration. Preclinical evaluations of inhaled anti-TB drugs, such as rifampicin, should include high-dose formulations in preclinical models, determined based on allometric conversions, for relevant high-dose anti-TB therapy in humans. Graphical abstract

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“…Porous materials as spherical particles have received a lot of attention lately for the numerous directions in which they can be used, such as in catalytic reactions, separation processes, consumer products (such as water softeners), biomedical devices, coating additives and controlled drug release systems [ 1 , 2 , 3 , 4 , 5 ]. As a polymer matrix, both natural [ 6 , 7 , 8 , 9 , 10 ] and synthetic polymers [ 11 , 12 , 13 , 14 , 15 ] can be used for the synthesis of porous microparticles.…”

Section: Introductionmentioning

confidence: 99%

Porous Crosslinked Zwitterionic Microparticles Based on Glycidyl Methacrylate and N-Vinylimidazole as Possible Drug Delivery Systems

Trofin¹,

Racoviţă²,

Vasiliu³

et al. 2022

IJMS

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Crosslinked porous microparticles have received great attention as drug delivery systems lately due to their unique set of properties: the capability to form various polymer–drug combinations, low immunogenicity, patient compliance and ability to release drugs in a delayed or controlled manner. Moreover, polymers with betaine groups have shown some unique features such as antifouling, antimicrobial activity, biocompatibility and strong hydration properties. Herein, novel porous zwitterionic microparticles were prepared in two stages. The first step involves the synthesis of porous microparticles based on glycidyl methacrylate, N-vinylimidazole and triethyleneglycol dimethacrylate using the suspension polymerization technique, the second step being the synthesis of zwitterionic porous microparticles by polymer–analogous reaction in presence of sodium monochloroacetate as betainization agent. Both types of microparticles were characterized structurally and morphologically by FT-IR spectroscopy, energy dispersive X-ray analysis, scanning electron microscopy, dynamic vapors sorption and mercury porosimetry. The tetracycline loading into crosslinked and zwitterionic microparticles was also performed, the maximum tetracycline loading capacities being 87 mg/g and 135 mg/g, respectively. The drug release mechanism, elucidated by various mathematical models, is controlled by both diffusion and swelling processes as a function of the zwitterionic and/or porous microparticle structure. Both types of microparticles presented antibacterial activity against the two reference strains used in this study: Escherichia coli and Staphylococcus aureus.

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Preparation, In Vitro Characterization, and In Vivo Pharmacokinetic Evaluation of Respirable Porous Microparticles Containing Rifampicin

Cited by 14 publications

References 22 publications

Drug-Loaded PLGA Electrospraying Porous Microspheres for the Local Therapy of Primary Lung Cancer via Pulmonary Delivery

Drug-Loaded PLGA Electrospraying Porous Microspheres for the Local Therapy of Primary Lung Cancer via Pulmonary Delivery

A review of formulations and preclinical studies of inhaled rifampicin for its clinical translation

Porous Crosslinked Zwitterionic Microparticles Based on Glycidyl Methacrylate and N-Vinylimidazole as Possible Drug Delivery Systems

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