Liposome-based carrier systems and devices used for pulmonary drug delivery

Khan, Iftikhar; Elhissi, Abdelbary; Shah, Mohak; Alhnan, Mohamed Albed; Ahmed, Waqar

doi:10.1533/9780857092205.395

Cited by 41 publications

(28 citation statements)

References 99 publications

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“…Small molecule cryoprotectants, such as glycerol or trehalose and other carbohydrates, can significantly reduce aggregation, fusion and leakage. Cryoprotectants have been successfully used to enhance the stability of liposomes to lyophilisation and rehydration [43]. However, this is notoriously challenging [44], and the potential for synergistic effects from cryoprotectants in the solution phase and block copolymers blended within hybrid vesicle membranes is a worthwhile avenue for future investigation.…”

Section: Discussionmentioning

confidence: 99%

“…During the freeze-drying process the product is frozen, thus immobilising the sample and allowing it to retain its original form, and then the water is removed by sublimation ( Figure 1c), preventing microbial growth [42]. For lipids, the absence of water would minimise the rate of hydrolysis during storage [43]. However lyophilisation of liposome formulations is challenging to maintain encapsulation and structural stability.…”

Section: Introductionmentioning

confidence: 99%

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Hybrid Vesicle Stability under Sterilisation and Preservation Processes Used in the Manufacture of Medicinal Formulations

et al. 2020

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Sterilisation and preservation of vesicle formulations are important considerations for their viable manufacture for industry applications, particular those intended for medicinal use. Here, we undertake an initial investigation of the stability of hybrid lipid-block copolymer vesicles to common sterilisation and preservation processes, with particular interest in how the block copolymer component might tune vesicle stability.We investigate two sizes of polybutadiene-block-poly(ethylene oxide) polymers (PBd 12 -PEO 11 and PBd 22 -PEO 14 ) mixed with the phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) considering the encapsulation stability of a fluorescent cargo and the colloidal stability of vesicle size distributions. We find that autoclaving and lyophilisation cause complete loss of encapsulation stability under the conditions studied here. Filtering through 200 nm pores appears to be viable for sterilisation for all vesicle compositions with comparatively low release of encapsulated cargo, even for vesicle size distributions which extend beyond the 200 nm filter pore size. Freeze-thaw of vesicles also shows promise for the preservation of hybrid vesicles with high block copolymer content. We discuss the process stability of hybrid vesicles in terms of the complex mechanical interplay between bending resistance, stretching elasticity and lysis strain of these membranes and propose strategies for future work to further enhance the process stability of these vesicle formulations.Polymers 2020, 12, 914 2 of 17 liposomes can have inherent instabilities. Their membranes are highly flexible under bending deformations, but weak under stretching deformations, with a lysis strain of less than 5% [28,29]. The labile fluidity of the membrane can lead to transient membrane defects that frustrates long term encapsulation stability and lipid peroxidation can cause chemical instabilities in these structures.Polymersomes, due to their synthetic nature, are often less biocompatible than their lipid counterparts but offer greater mechanical stability and a broader chemical parameter space [30]. Amphiphilic copolymers that form vesicles can have several different architectures, the most common being AB diblock (A = hydrophilic, B = hydrophobic) [6], ABA [31] and ABC tri-block polymers [32] where A and C are chemically different hydrophilic blocks and finally graft copolymers [33]. Formation of polymersomes depends on the amphiphilic co-polymers molecular weight, polydispersity and hydrophilic/hydrophobic block lengths ratio, which is ideally less than 1:3 to form vesicular structures [34]. Their membranes are often thicker than liposome membranes, which provides greater bending resistance and their enhanced elasticity under stretching makes them tough and durable [22]. The polymer chemistry can be designed to minimise chemical instability but also to incorporate novel functionality. In blending liposomes and polymersomes to create hybrid vesicles, the ambition is to combine advantageous properties of these m...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hybrid Vesicle Stability under Sterilisation and Preservation Processes Used in the Manufacture of Medicinal Formulations

et al. 2020

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“…Small molecule cryoprotectants such as glycerol or trehalose and other carbohydrates can significantly reduce aggregation, fusion and leakage. Cryoprotectant have been successfully used to enhance the stability of liposomes to lyophilisation and rehydration [39]. However this is notoriously challenging [40] and the potential for synergistic effects from cryoprotectants in the solution phase and block copolymers blended within hybrid vesicle membranes is a worthwhile avenue for future investigation.…”

Section: Discussionmentioning

confidence: 99%

“…1c), preventing microbial growth [38]. For lipids, the absence of water would minimise the rate of hydrolysis during storage [39]. However lyophilisation of liposome formulations is challenging to maintain encapsulation and structural stability.…”

mentioning

confidence: 99%

Hybrid Vesicle Stability under Sterilisation and Preservation Processes Used in the Manufacture of Medicinal Formulations

Seneviratne¹,

Jeuken²,

Rappolt³

et al. 2020

Preprint

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Sterilisation and preservation of vesicle formulations are an important consideration for their viable manufacture for industry applications, particular those intended for medicinal use. Here we undertake an initial investigation of the stability of hybrid lipid -block copolymer vesicles to common sterilisation and preservation processes, with particular interest in how the block copolymer component might tune vesicle stability. We investigate two sizes of polybutadiene-blockpoly(ethylene oxide) polymers (PBd12-PEO11 and PBd22-PEO14) mixed with the phospholipid POPC considering the encapsulation stability of a fluorescent cargo and the colloidal stability of vesicle size distributions. We find that autoclaving and lyophilisation cause complete loss of encapsulation stability under the conditions studied here. Filtering through 200 nm pores appears to be viable for sterilisation for all vesicle compositions with comparatively low release of encapsulated cargo, even for vesicle size distributions which extend beyond the 200 nm filter pore size. Freeze-thaw of vesicles also shows promise for preservation of hybrid vesicles with high block copolymer content. We discuss the process stability of hybrid vesicles in terms of the complex mechanical interplay between bending resistance, stretching elasticity and lysis strain of these membranes and propose strategies for future work to further enhance the process stability of these vesicle formulations.

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“…The carrier should be chosen on account of porosity and its capacity to accommodate phospholipids and drug moiety on its surface. Compared with conventional liposomal dispersions, proliposomes demonstrate more advantages in stability, solubility and drug release [19]. By knowing this situation, different inhalable proliposomes formulations have been designed and studied to enhance the aerodynamic performance and physical stability of various anti-TB drugs.…”

Section: Proliposomesmentioning

confidence: 99%

Potential of dry powder inhalers for tuberculosis therapy: facts, fidelity and future

Mehta

Bothiraja

Kadam

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Tuberculosis (TB) is a contagious and airborne infectious disease caused by the pathogen Mycobacterium tuberculosis (Mtb). In spite of substantial research efforts, continuous multiple high-dose drug therapy regularly for 4-7 months can impede patient quality of life. The pathology of TB and biology of pulmonary airways permits for a variety of drug delivery strategies and natural route of infection denotes a more logical remedial approach for treatment of TB. Pulmonary delivery is non-invasive, allow easy transcytosis in alveolar region, avoids first-pass metabolism and extensive vascularization facilitates delivery of therapeutic agents to infection site. It also potentially reduces the frequency with dose requirement and linked side effects. Dry powder is a most preferred inhalation option due to their greater physiochemical stability over liquid or suspension based formulations. Dry powder inhalers (DPIs) are easy to handle and appropriate for high-dose formulations. Moreover, the progress of disciplines such as nanotechnology, particle engineering, material science and molecular biology permits further expansion of treatment capability and efficiency. Thus, this article will focus on the role of novel DPIs systems for treatment of TB. This article also contains a dedicated section discussing about technical limitations and clinical challenges with help of strengths, weaknesses, opportunities and threats (SWOT) analysis. Additionally, it will also offer some basic background information for drug repurposing, formulation development and drug delivery systems.

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Liposome-based carrier systems and devices used for pulmonary drug delivery

Cited by 41 publications

References 99 publications

Hybrid Vesicle Stability under Sterilisation and Preservation Processes Used in the Manufacture of Medicinal Formulations

Hybrid Vesicle Stability under Sterilisation and Preservation Processes Used in the Manufacture of Medicinal Formulations

Hybrid Vesicle Stability under Sterilisation and Preservation Processes Used in the Manufacture of Medicinal Formulations

Potential of dry powder inhalers for tuberculosis therapy: facts, fidelity and future

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