Proliposome formulations for delivery via medical nebulisers

This study aims to investigate the ability of proliposomes to generate liposomes for delivery using air-jet, ultrasonic and vibrating-mesh nebulisers. Particulate-based proliposomes successfully generated liposomes under static conditions. Manually dispersed proliposomes generated multilamellar vesicles, with formulation having a small effect on the liposome size. Using sucrose as a carrier, liposomes were generated or dispersed in situ from proliposomes within the medical nebulisers investigated. The Pari (air-jet) and the Omron (vibrating-mesh) nebulisers produced large mass and lipid outputs with a large lipid fraction deposited in the lower stage of a two stage impinger. The Liberty (Ultrasonic) nebuliser failed to deliver more than 6% of the lipid employed. Multilamellar liposomes were generated from ethanol-based proliposomes. The resultant vesicles entrapped 62% of the available salbutamol sulphate compared to only 1.23% entrapped by liposomes made by the thin film method. Aeroneb Pro or Aeroneb Go vibrating-mesh nebulisers generated aerosol droplets of larger volume median diameter and narrower size distribution than the Pari (air-jet) nebuliser. Unlike the vibrating-mesh nebulisers, the performance of the jet nebuliser was largely independent of formulation. A nebuliser-dependent significant loss of the originally entrapped drug was demonstrated. A customised large mesh Aeroneb Pro reduced the drug losses during nebulisation. High sensitivity differential scanning calorimetry showed that the phospholipid phase transitions and liposomal bilayer interaction with beclometasone dipropionate were dependent on the method of liposome manufacture. Ethanol-based proliposomes produced liposomes having no pretransition, with a very low incorporation of the steroid (max. 1 mole%). This was attributed to an alcohol-induced interdigitation of the bilayers. 1 to 2.5 mole% steroid seemed to be optimal for incorporation in liposomes manufactured by the thin film or particulate-based proliposome method. Jet-nebulisation of particulate-based proliposomes delivered vesicles with enhanced steroid incorporation compared to liposomes generated by manual dispersion of these proliposomes

Role of Computerized Physician Order Entry Usability in the Reduction of Prescribing Errors

Some hospitals have implemented computerized physician order entry (CPOE) systems to reduce the medical error rates. However, research in this area has been very limited, especially regarding the impact of CPOE use on the reduction of prescribing errors. Moreover, the past studies have dealt with the overall impact of CPOE on the reduction of broadly termed "medical errors", and they have not specified which medical errors have been reduced by CPOE. Furthermore, the majority of the past research in this field has been either qualitative or has not used robust empirical techniques. This research examined the impacts of usability of CPOE systems on the reduction of doctors' prescribing errors. Methods: One hundred and sixty-six questionnaires were used for quantitative data analyses. Since the data was not normally distributed, partial least square path modelling-as the second generation of multivariate data analyses-was applied to analyze data. Results: It was found that the ease of use of the system and information quality can significantly reduce prescribing errors. Moreover, the user interface consistency and system error prevention have a significant positive impact on the perceived ease of use. More than 50% of the respondents believed that CPOE reduces the likelihood of drug allergy, drug interaction, and drug dosing errors thus improving patient safety. Conclusions: Prescribing errors in terms of drug allergy, drug interaction, and drug dosing errors are reduced if the CPOE is not error-prone and easy to use, if the user interface is consistent, and if it provides quality information to doctors

Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications

This was a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues related to mechanism of the nebulization and liposome composition were appraised and correlated with the literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was the liposome inhalation for the treatment of lung cancers. Many in-vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localize their action in the lung following pulmonary delivery. Safety of inhaled liposomes incorporating anticancer drug depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low dose reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases including pulmonary cancers. Successful development of anticancer liposomes for inhalation may depend on future development of effective aerosolization devices and better targeted liposomes to maximize benefit of therapy and reduce potential of local and systemic adverse effects

Paclitaxel loaded lipid nanoemulsions for the treatment of brain tumour

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Proliposome powder or tablets for generating inhalable liposomes using a medical nebulizer

Purpose: The aim of this study was to develop and compare proliposome powder and proliposome tablet formulations for drug delivery from a Pari-LC Sprint nebulizer. Methods: Proliposome powders were prepared by the slurry method and sorbitol or mannitol carbohydrate carrier were used in a 1:10 and 1:15 w/w lipid phase to carrier ratio. Beclometasone dipropionate (BDP; 2 mol%) was incorporated in the lipid phase. Proliposome powders were compressed into tablets, and liposomes were generated from proliposome powders or tablets within the nebulizer reservoir for subsequent aerosolization. Results: Comparatively, shorter sputtering times were reported for the tablet formulations (≈ < 2.7±0.45 min), indicating uniform aerosolization. Post-nebulization, liposomes size was larger in the nebulizer reservoir in the range of 7.79±0.48 µm–9.73±1.53 µm for both powder and tablet formulations as compared to freshly prepared liposomes (5.38±0.73 µm–5.85±0.86 µm), suggesting liposome aggregation/fusion in the nebulizer’s reservoir. All formulations exhibited more than 80% mass output regardless of formulation type, but greater BDP proportions (circa 50%) were delivered to the Two-stage Impinger when tablet formulations were used. Moreover, the nebulized droplet median size and size distribution were lower for all tablet formulations in comparison to the powder formulations. Proliposome tablet and powdered formulations demonstrated the ability to generate vesicles that sustained the release of BDP. Conclusion: Overall, this study showed that proliposome tablets could be disintegrated within a Pari-LC Sprint nebulizer to generate inhalable aerosol, with high drug output and hence can be manufactured on large scale to overcome the storage problems associated with powder formulations

RECENT ADVANCES IN APPLICATIONS OF ACTIVE CONSTITUENTS OF SELECTED MEDICINAL PLANTS OF DHOFAR, SULTANATE OF OMAN

 The Dhofar region of Oman is extremely opulent in plant biodiversity in comparison to other parts of the country. Most of the cultivated, medicinal and wild plants of the region are available in the mountainous side and hilly areas of Dhofar. The plants produce products from primary metabolism and others from secondary metabolism. On the basis of active constituents plants can be categorized into two groups:1. Medicinal plants and2. Aromatic plants.Over 250 complex chemicals have been recognized and extracted from herbal sources. In this review article, we discuss a selection of medicinal plants of the Dhofar region of Oman which are rich in active constituents and through recent reports discuss the application of the most active constituents. Among the medicinal plants of the Dhofar region, frankincense is also a well-known indicator of the region and has a unique position through its medicinal properties of its oil and gum resin

Editorial: Anti-cancer drug delivery: lipid-based nanoparticles

Cancer continues to pose significant challenges that require extensive attention and efforts from the scientific community. The battle against cancer encompasses the development of effective and safe therapeutic approaches. However, achieving this balance is highly complex for anticancer therapies, as they often exhibit intense intrinsic cytotoxicity, affecting both cancerous and healthy cells and resulting in substantial toxicity that limits their clinical utility. A promising strategy to address this challenge involves the selective guidance of therapeutic agents to the cancer site, minimizing off-target effects. Nanotechnology offers powerful tools to engineer smart and targeted therapeutics that preferentially accumulate in cancerous tissues . This preferential localization is achieved through the Enhanced Permeation and Retention (EPR) effect, first reported by Prof. Hiroshi Maeda in 1984 . The EPR effect leverages the leaky vasculature in tumor regions, enabling enhanced infiltration of nanotherapeutics and localizing their therapeutic effects, which is commonly described as "passive targeting ". On the other hand, nanotechnologists may also employ "active targeting" by modifying nanoparticle surfaces with homing ligands that selectively recognize cancer cells . Both passive and active targeting strategies are keys for success of nanoparticle-based drug delivery systems, and serve as a justification for the development of nanotherapeutics. Extensive literature exists on various types of nanoparticles and nanomaterials with potential applications as drug delivery systems.The authors would like to thank to the journal (Frontiers in Oncology) for providing us this opportunity to organize the research topic on "Anti-Cancer Drug Delivery: Lipid-Based Nanoparticles". We thank all the authors who contributed in this topic collection. We are also, very grateful to all the reviewers who participated in the whole manuscript review process.Scopu

PEGylated graphene oxide for tumor-targeted delivery of paclitaxel.

AIM: The graphene oxide (GO) sheet has been considered one of the most promising carbon derivatives in the field of material science for the past few years and has shown excellent tumor-targeting ability, biocompatibility and low toxicity. We have endeavored to conjugate paclitaxel (PTX) to GO molecule and investigate its anticancer efficacy. MATERIALS & METHODS: We conjugated the anticancer drug PTX to aminated PEG chains on GO sheets through covalent bonds to get GO-PEG-PTX complexes. The tissue distribution and anticancer efficacy of GO-PEG-PTX were then investigated using a B16 melanoma cancer-bearing C57 mice model. RESULTS: The GO-PEG-PTX complexes exhibited excellent water solubility and biocompatibility. Compared with the traditional formulation of PTX (Taxol®), GO-PEG-PTX has shown prolonged blood circulation time as well as high tumor-targeting and -suppressing efficacy. CONCLUSION: PEGylated graphene oxide is an excellent nanocarrier for paclitaxel for cancer targeting

Paclitaxel-loaded Micro or Nano Transfersome Formulation into Novel Tablets for Pulmonary Drug Delivery via Nebulization

A simplistic approach was conducted to manufacture novel paclitaxel (PTX) loaded protransfersome tablet formulations for pulmonary drug delivery. Large surface area presented by pulmonary system offer better target using anti-cancer drug deposition for localized effect in the lungs. Protransfersomes are dry powder formulations, whereas transfersomes are liquid dispersions containing vesicles generated from protransfersomes upon hydration. Protransfersome powder formulations (F1 – F27) (referred as Micro formulations based on transfersomes vesicles size post hydration) were prepared by employing phospholipid (Soya phosphatidylcholine (SPC)), three different carbohydrate carriers (Lactose monohydrate, LMH; Microcrystalline cellulose, MCC; and Starch), three surfactants (i.e. Span 80, Span 20 and Tween 80) in three different lipid phase to carrier ratios (i.e. 1:05, 1:15 and 1:25 w/w), with the incorporation of PTX as a model drug. Hydrophobic chain of SPC may enhance PTX solubility as well as its accommodation to improve entrapment and delivery via transfersome vesicles to the target site. Out of the 27 Micro protransfersome formulations, PTX-loaded LMH powder formulations F3, F6 and F9 (i.e. 1:25 w/w lipid phase to carrier ratio) exhibited an excellent powder flowability via angle of repose (AOR) and good compressibility index due to the smaller and uniform particle size and shape of LMH. Following hydration, these formulations also showed smaller volume median diameter (VMD) in micrometres (5.65 ± 0.85 – 6.76 ± 0.61 µm) and PTX entrapment of 93 – 96%. Hydrated transfersome formulations (F3, F6 and F9) were converted into Nano size via probe sonication and referred as Nano formulations. These Nano formulations were converted into dry powder via spray drying (SD) (F3NSD, F6NSD and F9NSD) or freeze drying (FD) (F3NFD, F6NFD and F9NFD). Post manufacture of protransfersome tablets (i.e. 9 formulations), quality control tests were conducted in accordance to British Pharmacopeia (BP). Only Micro formulations protransfersome tablets (i.e. F3, F6 and F9) passed the uniformity of weight test, exhibited high crushing strength and tablet thickness when compared to SD or FD protransfersome tablets. Micro protransfersome formulations (i.e. F3, F6 and F9) into tablets demonstrated shorter nebulization time and high output rate using Ultrasonic nebulizer as compared to Vibrating mesh nebulizer (i.e. Omron NE U22). Based on formulations, characterizations and nebulizer performance; Micro protransfersome tablet formulations F3, F6 and F9 (i.e. 1:25 w/w) and Ultrasonic nebulizer was found to be a superior combination with enhanced output efficiency. Moreover, PTX-loaded F3, F6 and F9 tablet formulations (10%) were identified as toxic (60, 68 and 67% cell viability) to cancer MRC-5 SV2 (i.e. immortalized human lung cells) while safe to MRC-5 (normal lung fibroblast cells) cell lines