Inhaled Solid Lipid Microparticles to target alveolar macrophages for tuberculosis

Maretti, Eleonora; Rossi, Tiziana; Bondi, Moreno; Croce, Maria Antonietta; Hanuskova, Miriam; Leo, Eliana Grazia; Sacchetti, Francesca; Iannuccelli, Valentina

doi:10.1016/j.ijpharm.2013.12.034

Cited by 74 publications

(25 citation statements)

References 46 publications

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“…As a consequence of the several side effects along with the lengthy treatment period, there is a low adherence to drug administration schedules, which facilitates the development of multi-drug resistant tuberculosis. [9] Several side effects of RIF are related to its pharmacokinetics, mainly to its low solubility in water. [10][11][12] Under gastric conditions, RIF suffers hydrolysis leading to even less soluble compounds such as 3-formyl-rifampicin.…”

Section: Introductionmentioning

confidence: 99%

“…[13,14] In order to improve the bioavailability of RIF and the other tuberculostatic drugs, several research groups have been developing drug delivery systems (DDS). [12] Suggested formulations involve hydrosoluble polymers, [15][16][17][18][19] solid dispersions, [20] microparticles, [9] liposomes, [21,22] inclusion complexes [23,24] and dendrimers [25]. Ideally, a DDS would transport the active compounds to their targets, reducing the therapeutic dosage while keeping the desired drug level for a long period of time, minimizing adverse effects and simplifying the treatment.…”

Section: Introductionmentioning

confidence: 99%

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Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Bellini

Guimarães

Pacheco

et al. 2015

Journal of Molecular Graphics and Modelling

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The association of the anti-tuberculosis drug rifampicin (RIF) with a 4th-generation poly(amidoamine) (G4-PAMAM) dendrimer was investigated by means of molecular dynamics simulations. The RIF load capacity was estimated to be around 20 RIF per G4-PAMAM at neutral pH. The complex formed by 20 RIF molecules and the dendrimer (RIF20-PAMAM) was subjected to 100 ns molecular dynamics (MD) simulations at two different pH conditions (neutral and acidic). The complex was found to be significantly more stable in the simulation at neutral pH compared to the simulation at low pH in which the RIF molecules were rapidly and almost simultaneously expelled to the solvent bulk. The high stability of the RIF-PAMAM complex under physiological pH and the rapid release of RIF molecules under acidic medium provide an interesting switch for drug targeting since the Mycobacterium resides within acidic domains of the macrophage. Altogether, these results suggest that, at least in terms of stability and pH-dependent release, PAMAM-like dendrimers may be considered suitable drug delivery systems for RIF and derivatives.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

Bellini

Guimarães

Pacheco

et al. 2015

Journal of Molecular Graphics and Modelling

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“…In vitro studies on J774 cell lines reported that SLMs as non-cytotoxic and ability to be taken up by cell cytoplasm. The SLMs, showed features suitable for the pulmonary delivery and for inducing endocytosis by alveolar macrophages, for this reason, it may possibly be considered as a promising efficacious TB therapy using a Dry Powder Inhaler device [60]. Smaller particle size with improved sustained release properties was observed with RIF encapsulated microparticles.…”

Section: Solid Lipid Microparticlesmentioning

confidence: 99%

Exploring the Use of Lipid Based Nano-Formulations for the Management of Tuberculosis

Cm¹,

Cd²,

M³

et al. 2017

J Nanosci Curr Res

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Tuberculosis (TB) is an airborne infectious disease spreading very fast from person to person, which affect the health as well as socioeconomic conditions harshly. Though varieties of antitubercular drugs (ATDs) are available for its treatment, associated stern side effects restrict the patients to receive complete therapeutic benefits. Moreover, emergence of drug-resistant tuberculosis and co-infection of TB with HIV further worsen the situations. Polymeric formulations are introduced for progressive and long-term delivery of therapeutic agents, but owing to their noted limitations, performance is not up to the mark. In this juxtaposition, lipid based nano-formulations are introduced as an alternative to the polymic formulations in the management of TB with an intention to overcome side effects related to drugs along with limitations of polymeric formulations. The lipid based formulations comprise nanoemulsions, solid-lipid nanoparticles (SLNs), nano-structured lipid carriers (NLCs), liposomes, and niosomal systems, etc.Liposomes have more promising antitubercular activity as its intended for targeted drug delivery especially to the infected part. Further mannosylation of liposomes offers tremendous results in TB chemotherapy as it directly binds to mannose receptors available on the surface of alveolar macrophages resulting mycobacterium destruction. Niosomes may have superior drug targeting ability, chemical stability, osmotic activeness and in vivo activity in comparison to that of liposomes. SLNs and manosylated SLNs are the advanced form of the lipid formulations which enhance the drug uptake at the infected organ and show significant in vivo anti-tubercular activity with reduced toxicity. Moreover, NLCs shows its satisfactory potential against MTb along with drug targeting action. Advancement on the development of miscellaneous or other vesicular lipid formulations are not encouraging in the field of tubercular chemotherapy. Hence, lipid based formulations could be successfully employed for targeted delivery of ATDs with promising anti-tubercular activity.

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“…Equally, solid lipid particles can be formed as solid lipid microparticles (SLMs) for suitability in a range of applications. These SLMs can provide acceptable aerodynamic for pulmonary delivery and a negative surface charge to promote phagocytosis as shown in the murine macrophages cell line J774 [19]. Research has been carried out to combine a solid polymer-based core with an external lipid coating thereby combining the benefits of each system such as the biological compatibility of the external lipid coating with the increased stability of the polymer core to protect any delivered therapeutics.…”

Section: Lipid Based Drug Delivery Systemsmentioning

confidence: 99%