Inhalable DNase I microparticles engineered with biologically active excipients

Osman, Rihab; Al‐Jamal, Khuloud T.; Kan, Pei-Lee; Awad, Gehanne A.S.; Mortada, Nahed D.; EL-Shamy, Abd-Elhameed; Alpar, Oya

doi:10.1016/j.pupt.2013.07.010

Cited by 20 publications

(18 citation statements)

References 38 publications

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“…Aggregation could be avoided by adding excipients to the formulations as lubricant agents such as magnesium stearate (O'Connor et al 2019) and oleic acid (Cocks et al 2015). Protein stabilizer, as divalent ions, ovalbumin and hydroxyl propyl-βcyclodextrin,or other excipients, as trehalose or Tween, have been successfully used to improve protein and enzyme stabilities into PLGA MPs (Osman et al 2013). Conversely, one of the most critical aspects is the employment of toxic reactive as organic solvents (i.e., dichloromethane or chloroform) (Table 2); consequently, there is a great interest in developing greener and safer procedures when preparing PLGA MPs (Sah 2000).…”

Section: Introductionmentioning

confidence: 99%

Recent advances in the formulation of PLGA microparticles for controlled drug delivery

et al. 2020

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Polymeric microparticles (MPs) are recognized as very popular carriers to increase the bioavailability and bio-distribution of both lipophilic and hydrophilic drugs. Among different kinds of polymers, poly-(lactic-co-glycolic acid) (PLGA) is one of the most accepted materials for this purpose, because of its biodegradability (due to the presence of ester linkages that are degraded by hydrolysis in aqueous environments) and safety (PLGA is a Food and Drug Administration (FDA)-approved compound). Moreover, its biodegradability depends on the number of glycolide units present in the structure, indeed, lower glycol content results in an increased degradation time and conversely a higher monomer unit number results in a decreased time. Due to this feature, it is possible to design and fabricate MPs with a programmable and time-controlled drug release. Many approaches and procedures can be used to prepare MPs. The chosen fabrication methodology influences size, stability, entrapment efficiency, and MPs release kinetics. For example, lipophilic drugs as chemotherapeutic agents (doxorubicin), anti-inflammatory non-steroidal (indomethacin), and nutraceuticals (curcumin) were successfully encapsulated in MPs prepared by single emulsion technique, while water-soluble compounds, such as aptamer, peptides and proteins, involved the use of double emulsion systems to provide a hydrophilic compartment and prevent molecular degradation. The purpose of this review is to provide an overview about the preparation and characterization of drug-loaded PLGA MPs obtained by single, double emulsion and microfluidic techniques, and their current applications in the pharmaceutical industry. Graphic abstract

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Section: Introductionmentioning

confidence: 99%

Recent advances in the formulation of PLGA microparticles for controlled drug delivery

et al. 2020

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“…In addition to the composition of the feed formulation, several operational parameters greatly affect the quality and quantity of the final formulation such as inlet temperature, air flow, aspiration capacity and feed rate . Biocompatible excipients (carbohydrates, amino acids and lipids) are typically added to the formulation feed to afford dry powders with bulk and to promote the production of a desirable aerodynamic particle size which upon inhalation allows rapid release of NPs in the lung fluid . In addition, the excipients can protect the NPs and encapsulated agents against the extreme spray‐drying process conditions such as high temperatures and shear forces .…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers

Alfagih

Kunda

Alanazi

et al. 2015

Journal of Pharmaceutical Sciences

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Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immunocompromised, the very young and the old, and remains one of the leading causes of death. A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S. pneumoniae, pneumococcal surface protein A (PspA) that has shown cross-reactivity amongst serotypes to be delivered via the pulmonary route has been formulated. The formulation contains the antigen PspA adsorbed onto the surface of polymeric nanoparticles encapsulated in L-leucine microparticles that can be loaded into capsules and delivered via an inhaler. We have successfully synthesized particles of ∼150 nm and achieved ∼20 μg of PspA adsorption per mg of NPs. In addition, the spray-dried powders displayed a FPF of 74.31 ± 1.32% and MMAD of 1.70 ± 0.03 μm suggesting a broncho-alveolar lung deposition facilitating the uptake of the nanoparticles by dendritic cells. Also, the PspA released from the dry powders maintained antigen stability (SDS-PAGE), integrity (Circular dichroism) and activity (lactoferrin binding assay). Moreover, the released antigen also maintained its antigenicity as determined by ELISA. Graphical abstractPlease cite this article as: Kunda, Nitesh K., Alfagih, Iman M., Miyaji, Eliane N.

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“…This would account for up-regulation in genes coding for transporter proteins which would not have necessarily been anticipated as a result of interaction with the API alone. This lends strength to the recently developing ideology that excipients potentially possess biological activity and are not inactive ingredients [28,29].…”

Section: Assessment Of Absorption In Vitromentioning

confidence: 90%

Paediatric drug development of ramipril: reformulation,in vitroandin vivoevaluation

Russell

Begum²,

Hussain³

et al. 2015

Journal of Drug Targeting

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Ramipril is used mainly for the treatment of hypertension and to reduce incidence of fatality following heart attacks in patients who develop indications of congestive heart failure. In the paediatric population, it is used most commonly for the treatment of heart failure, hypertension in type 1 diabetes and diabetic nephropathy. Due to the lack of a suitable liquid formulation, the current study evaluates the development of a range of oral liquid formulations of ramipril along with their in vitro and in vivo absorption studies. Three different formulation development approaches were studied: solubilisation using acetic acid as a co-solvent, complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) and suspension development using xanthan gum. Systematic optimisation of formulation parameters for the different strategies resulted in the development of products stable for 12 months at long-term stability conditions. In vivo evaluation showed C(max) of 10.48 µg/ml for co-solvent, 13.04 µg/ml for the suspension and 29.58 µg/ml for the cyclodextrin-based ramipril solution. Interestingly, both ramipril solution (co-solvent) and the suspension showed a T(max) of 2.5 h, however, cyclodextrin-based ramipril produced T(max) at 0.75 h following administration. The results presented in this study provide translatable products for oral liquid ramipril which offer preferential paediatric use over existing alternatives.

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Inhalable DNase I microparticles engineered with biologically active excipients

Cited by 20 publications

References 38 publications

Recent advances in the formulation of PLGA microparticles for controlled drug delivery

Recent advances in the formulation of PLGA microparticles for controlled drug delivery

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers

Paediatric drug development of ramipril: reformulation,in vitroandin vivoevaluation

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