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

TOPICAL DELIVERY OF QUERCETIN LOADED TRANSFERSOMES FOR WOUND TREATMENT: IN VITRO AND IN VIVO EVALUATION

Objective: To design topical Quercetin (Qc)-loaded transfersomes (TFs) for wound treatment. Methods: Qc-loaded TFs were prepared by thin-film hydration technique using 2241full factorial design and the optimum formula was selected. In vivo skin, deposition and cutaneous wound induction studies were performed for four groups of male wistar rats. At the end of the experiment, biochemical parameters were measured in the healed tissues (total proteins (TP), total antioxidant capacity (TAC), glutathione reductase (GSH), nitric oxide (NO), and malonaldehyde (MDA). Two in vivo histopathological experiments using male wistar rats were performed; the first study was done for the healed tissues of the above experiment and the second was to confirm the safety of formulations. Results: Qc optimum TFs (F6) showed EE% of 91.1%, PS of 695.35 nm, PDI of 0.592, and ZP of-11.1 mV, and spherical shape. In vivo skin deposition study showed that drug percentage retained in the skin from Qc optimum TFs was significantly higher than that from Qc suspension and Qc liposomes (p<0.05). There was no significant difference in the values of TP, TAC and MDA between the treated groups (p>0.05). GSH in TFs treated groups was significantly higher than the other groups (p<0.05) while NO in TFs treated groups was significantly lower than the other treated groups (p<0.05). Histopathological experiments showed that wounds treated by TFs healed better than those treated by both liposomes and Qc suspension. Conclusion: Qc-loaded TFs can be used as successful drug-delivery system for wound healing

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

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

Paclitaxel loaded lipid nanoemulsions for the treatment of brain tumour

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Pelvic Positioning in the Supine Position Leads to More Consistent Cup Orientation after Total Hip Arthroplasty

Aims: This study aims to 1) Determine the difference in pelvic position that occurs between surgery and radiographic, supine, post-operative assessment; 2) Examine how the difference in pelvic position influences subsequent cup orientation and 3) Establish whether pelvic position, and thereafter cup orientation differences exist between THAs performed in the supine versus the lateral decubitus positions. Materials and Methods: 321 THAs who had intra-operative, post-cup impaction, AP pelvic radiograph, in the operative position were studied; 167 were performed with patient supine (anterior approach), whilst 154 were performed in lateral decubitus (posterior approach). Cup inclination/anteversion was measured from intra- and post-operative radiographs and difference (Δ) was determined. The target zone was inclination/anteversion of 40/20°±10°. Change in pelvic position (tilt, rotation, obliquity) between surgery and post-operatively was calculated from Δinclination/anteversion using the Levenberg-Marquardt algorithm. Results: The post-operative inclination/anteversion was 40°±8/23°±9. 74 had Δinclination and/or Δanteversion&gt;±10° (21%). Intra-operatively (compared to post-operative), the pelvis was on average 4°±10 anteriorly tilted; 1°±10 internally rotated and 1°±5 adducted. Having Δinclination and/or Δanteversion &gt;±10° was associated with a 3.5 odds ratio of having a cup outside the target. A greater proportion of hips operated in the lateral decubitus had Δinclination and/or Δanteversion &gt;±10° (54/153), compared to supine (8/167) (p&lt;0.001). A greater number of cups achieved the target orientation in supine (120/167;73%), compared to lateral position (67/153;44%) (p&lt;0.001). Intra-operatively, pelvis was more anteriorly tilted (p&lt;0.001) and hemi-pelvis was more internally rotated (p=0.04) in lateral position. Conclusion: Pelvic movement is significantly less in supine position, which leads to more consistent cup orientation. Significant differences in pelvic tilt and rotation were seen in the lateral position. Clinical Relevance: Understanding the differences in pelvic orientation and cup orientation between supine and lateral decubitus positions may facilitate better intraoperative practices for surgeons