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In vitro evaluation of the inhalable quercetin loaded nanoemulsion for pulmonary delivery

Arbain NH, Salim N, Masoumi HRF, Wong TW, Basri M, Abdul Rahman MB

Drug Deliv Transl Res, 2019 04;9(2):497-507.
PMID: 29541999 DOI: 10.1007/s13346-018-0509-5

Bioavailability of quercetin, a flavonoid potentially known to combat cancer, is challenging due to hydrophobic nature. Oil-in-water (O/W) nanoemulsion system could be used as nanocarrier for quercertin to be delivered to lung via pulmonary delivery. The novelty of this nanoformulation was introduced by using palm oil ester/ricinoleic acid as oil phase which formed spherical shape nanoemulsion as measured by transmission electron microscopy and Zetasizer analyses. High energy emulsification method and D-optimal mixture design were used to optimize the composition towards the volume median diameter. The droplet size, polydispersity index, and zeta potential of the optimized formulation were 131.4 nm, 0.257, and 51.1 mV, respectively. The formulation exhibited high drug entrapment efficiency and good stability against phase separation and storage at temperature 4 °C for 3 months. It was discovered that the system had an acceptable median mass aerodynamic diameter (3.09 ± 0.05 μm) and geometric standard deviation (1.77 ± 0.03) with high fine particle fraction (90.52 ± 0.10%), percent dispersed (83.12 ± 1.29%), and percent inhaled (81.26 ± 1.28%) for deposition in deep lung. The in vitro release study demonstrated that the sustained release pattern of quercetin from naneomulsion formulation up to 48 h of about 26.75% release and it was in adherence to Korsmeyer's Peppas mechanism. The cytotoxicity study demonstrated that the optimized nanoemulsion can potentially induce cyctotoxicity towards A549 lung cancer cells without affecting the normal cells. These results of the study suggest that nanoemulsion is a potential carrier system for pulmonary delivery of molecules with low water solubility like quercetin.

Matched MeSH terms: Administration, Inhalation
Fulltext Comparison of effectiveness and time-efficiency between multimedia and conventional counselling on metered-dose inhaler technique education

King TL, Kho EK, Tiong YH, Julaihi SN

Singapore Med J, 2015 Feb;56(2):103-8.
PMID: 25715856

INTRODUCTION: This study aimed to evaluate whether multimedia counselling (MC) using a touchscreen computer is as effective and time-efficient as conventional counselling (CC) in promoting correct metered-dose inhaler (MDI) technique, with or without the valved holding chamber (VHC).

METHODS: Participants in the MDI-only and MDI-with-VHC groups were randomly assigned to the MC group or CC group. No blinding was imposed. Inhalation technique was assessed using checklists before and after counselling. Time spent on counselling was determined for all participants, while time taken to perfect the technique was determined only for participants who achieved perfect technique within one hour.

RESULTS: The CC group had more elderly participants than the MC group, but the difference was not significant. MDI-only and MDI-with-VHC users showed significant improvement in their inhaler technique after multimedia (44.5 ± 28.0% and 44.1 ± 14.4%, respectively) and conventional counselling (36.8 ± 20.5% and 37.0 ± 14.6%, respectively). No significant difference in MDI technique enhancement was found between the two groups. Although no significant difference was found between the MC and CC groups with regard to the time spent on counselling and the time taken to perfect the technique, the average time spent on counselling was longer for MDI-only users. MDI-only users had 13.5 times the odds of failing to achieve perfect technique compared to MDI-with-VHC users (95% confidence interval 1.50-121.32, p = 0.020).

CONCLUSION: MC and CC significantly improved MDI technique. Both methods showed comparable short-term effectiveness and time-efficiency in MDI technique education. VHC was beneficial, especially for MDI-users with hand-lung coordination problems.

Matched MeSH terms: Inhalation
Fulltext The incidence of inhaled foreign body in West Malaysia

Shanmugham MS

Singapore Med J, 1984 Feb;25(1):52-3.
PMID: 6463665

In this paper the incidence of inhaled foreign body in the tracheobronchial tree at the University Hospital Kuala Lumpur, West Malaysia, is reviewed. Children are the usual victims. Food·related substance (peanut) is the most common foreign body, Successful removal of foreign body by bronchoscopy is achieved in the great majority of cases (86%), Prevention can be achieved by educating the parents not to give nuts to children below the age of 3 years.

Matched MeSH terms: Inhalation
Can patients achieve sufficient peak inspiratory flow rate (PIFR) with Turbuhaler® during acute exacerbation of asthma?

Mohd Rhazi NA, Muneswarao J, Abdul Aziz F, Ibrahim B, Kamalludin A, Soelar SA

J Asthma, 2023 Aug;60(8):1608-1612.
PMID: 36650693 DOI: 10.1080/02770903.2023.2169930

INTRODUCTION: Anti-inflammatory reliever (AIR) with or without regular maintenance delivered through Turbuhaler® has been widely recommended in the GINA strategy document. These patients are not prescribed with additional reliever inhalers, but dependent on Turbuhaler® during acute asthma episodes. The peak inspiratory flow rate (PIFR) is crucial in drug delivery from a dry powder inhaler (DPI) such as Turbuhaler®. Despite its increasing usage, there are some concerns that patients on Turbuhaler® are not able to achieve adequate PIFR during acute exacerbation of asthma.
OBJECTIVE: This study aimed to assess the PIFR at resistance settings that matched Turbuhaler® in patients with acute exacerbation of asthma.
METHODOLOGY: A six-month cross-sectional study was conducted at the Emergency Department (ED) of Hospital Sultanah Bahiyah and Hospital Kulim, Kedah, Malaysia. Adult patients diagnosed with mild to moderate acute exacerbations of asthma were recruited. The PIFRs were measured using the In-Check DIAL G16 that was set to simulate the resistance of Turbuhaler® (R3). The PIFRs were assessed before (pre) and after (post) the initial bronchodilator (BD) treatment at the ED. The minimal required PIFR was defined as flow rates ≥ 30 L/min while a PIFR of 60 L/min was considered as optimal.
RESULTS: A total of 151 patients (81 females and 70 males) were recruited. The mean age was 37.5 years old with a range between 18 and 79 years old. The results showed that 98% (n = 148) of patients managed to achieve the minimal PIFR required for pre-BD. The mean PIFR pre-BD was 60 ± 18.5 L/min and post-BD was 70 ± 18.5 L/min. Furthermore, more than half (54%, n = 82) of the patients recorded PIFR ≥ 60 L/min during pre-BD, and about three-quarters (71%, n = 92) achieved PIFR ≥ 60 L/min post-BD. The PIFR showed a moderate correlation with peak expiratory flow rate (PEFR) (r = 0.55, 95% CI: 0.43-0.65, p

Matched MeSH terms: Administration, Inhalation
Fulltext Development and characterization of a spray-dried inhalable ternary combination for the treatment of Pseudomonas aeruginosa biofilm infection in cystic fibrosis

Alhajj N, Yahya MFZR, O'Reilly NJ, Cathcart H

Eur J Pharm Sci, 2024 Jan 01;192:106654.
PMID: 38013123 DOI: 10.1016/j.ejps.2023.106654

Cystic fibrosis (CF) is an inherited lung disease characterised by the accumulation of thick layers of dried mucus in the lungs which serve as a nidus for chronic infection. Pseudomonas aeruginosa is the predominant cause of chronic lung infection in cystic fibrosis. The dense mucus coupled with biofilm formation hinder antibiotic penetration and prevent them from reaching their target. Mucoactive agents are recommended in the treatment of CF in combination with antibiotics. In spite of the extensive research in developing novel drug combinations for the treatment of lung infection in CF, to our knowledge, there is no study that combines antibiotic, antibiofilm and mucoactive agent in a single inhaled dry powder formulation. In the present study, we investigate the possibility of adding a mucoactive agent to our previously developed ciprofloxacinquercetin (antibiotic-antibiofilm) dry powder for inhalation. Three mucoactive agents, namely mannitol (MAN), N-acetyl-L-cysteine (NAC) and ambroxol hydrochloride (AMB), were investigated for this purpose. The ternary combinations were prepared via spray drying without the addition of excipients. All ternary combinations conserved or improved the antibacterial and biofilm inhibition activities of ciprofloxacin against P. aeruginosa (ATCC 10145). The addition of AMB resulted in an amorphous ternary combination (SD-CQA) with superior physical stability as indicated by DSC and nonambient XRPD. Furthermore, SD-CQA displayed better in vitro aerosolization performance (ED ∼ 71 %; FPF ∼ 49 %) compared to formulations containing MAN and NAC (ED ∼ 64 % and 44 %; FPF ∼ 44 % and 29 %, respectively). In conclusion, a ternary drug combination powder with suitable aerosolization, physical stability and antibacterial/antibiofilm properties was prepared by a single spray drying step.

Matched MeSH terms: Administration, Inhalation
Fulltext Surfactant therapy in respiratory distress syndrome--the first local experience

Lim NL, Nordin MM, Cheah IG

Med J Malaysia, 1994 Mar;49(1):4-11.
PMID: 8057989

An open prospective descriptive pilot study was undertaken to assess the effectiveness and experience in the use of ExosurfNeonatal, a synthetic surfactant, on preterm infants with respiratory distress syndrome in the neonatal intensive care unit of the Paediatric Institute. Of 10 infants treated, seven (70%) survived with no major handicap on discharge. The mean duration of ventilation for these survivors was 6.4 days, mean duration of oxygen therapy 9.1 days and mean length of hospital stay 38.3 days. A comparison was made with a retrospective analysis of 15 neonates who were admitted during an eight month period prior to the pilot study. These infants were mechanically ventilated for respiratory distress syndrome but not given surfactant therapy. Of these, nine (60%) survived (P > 0.1 compared to Exosurf treated infants), but two developed post haemorrhagic hydrocephalus requiring shunting. For these nine survivors, the mean duration of ventilator therapy was 12.6 days, the mean duration of oxygen therapy 20.7 days and the mean length of hospital stay 70.8 days. This difference was statistically significant (P < 0.05). Of the three ExosurfNeonatal treated infants who died, two were extremely premature. Both developed grade IV periventricular haemorrhage while the third infant was admitted in shock and hypothermia and died from intraventricular haemorrhage and pulmonary interstitial emphysema. Except for the very sick and extremely premature infants, surfactant therapy is useful in reducing the mortality and morbidity of premature infants with respiratory distress syndrome in our neonatal intensive unit.

Matched MeSH terms: Oxygen Inhalation Therapy/statistics & numerical data
Retinopathy of prematurity in very low birth weight infants

Chye JK, Lim CT, Leong HL, Wong PK

Ann Acad Med Singap, 1999 Mar;28(2):193-8.
PMID: 10497665

This study aims to determine the prevalence of and risk factors associated with retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants. All premature VLBW infants, admitted into the neonatal intensive care unit of the University Hospital Kuala Lumpur, were screened from 4 weeks of life. Perinatal and neonatal data were retrieved from the infants' medical notes. Between August 1994 and July 1996, 100 infants had their eyes examined serially. Of the 15 (15%) infants with ROP, all were less than 31 weeks gestation, and only 1 infant had birth weight above 1250 g. Five (5%) infants had severe ROP; 4 infants underwent cryotherapy for stage 3 threshold disease. Infants with ROP, as compared to infants without ROP, had lower birth weight [mean (SEM) 993 (50) g versus 1205 (22) g, P < 0.001], lower gestational age [mean (SEM) 28.0 (0.4) weeks versus 30.1 (0.2) weeks, P < 0.001], higher rates of patent ductus arteriosus and chronic lung disease, greater number of radiographic examinations and episodes of late-onset suspected/confirmed sepsis, and required longer duration of supplemental oxygen, ventilation, xanthine, antibiotics and intralipid use, but were slower to establish full enteral feeds. On multivariate logistic regression analysis, birth weight < or = 1000 g [OR 2.38, 95% CI 1.25, 4.55, P = 0.009] and gestational age < or = 28 weeks [OR 2.86, 95% CI 1.47, 5.56, P = 0.002] were significant predictors of increased risk of this disease. In conclusion, ROP is strongly associated with smaller, more immature and sicker neonates. Prevention of prematurity would help reduce the incidence of this disease.

Matched MeSH terms: Oxygen Inhalation Therapy/statistics & numerical data
Lack of neutrophil degranulation in low-dose endotoxin inhalation based on a novel intracellular assay

Loh LC, Lo WH, Kanabar V, O'Connor BJ

Asian Pac J Allergy Immunol, 2006 Jun-Sep;24(2-3):153-60.
PMID: 17136881

To study the nature of endotoxin or lipopolysaccharide (LPS) induced inflammation, we developed a method of quantifying intracellular human neutrophil elastase (HNE) in lysed sputum polymorphs as a means to study the degranulation status of LPS-recruited neutrophils. Induced sputum, blood and exhaled nitric oxide (NO) were collected from 10 healthy non-atopic human subjects after inhaling a single 15 microg dose of Escherichia coil LPS in an open study. At 6 hours, LPS inhalation caused significant increase of sputum and blood neutrophils but without parallel increase in myeloperoxidase, HNE or interleukin-8 (IL-8) in sputum sol and blood, or exhaled NO. Intracellular HNE in lysed sputum polymorphs or purified blood neutrophils did not show any significant changes between inhaled LPS and saline, nor was there any appreciable change in percentage HNE release induced by N-Formyl-Met-Leu-Phe (fMLP) in vitro. We concluded that in healthy humans, the transient neutrophilic inflammation induced by a single dose of inhaled 15 microg LPS is mainly characterized by cell recruitment, not enhanced secretion of granular mediators or increased exhaled NO based on our experimental conditions.

Matched MeSH terms: Administration, Inhalation
A comparison of sputum induction methods: ultrasonic vs compressed-air nebulizer and hypertonic vs isotonic saline inhalation

Loh LC, Eg KP, Puspanathan P, Tang SP, Yip KS, Vijayasingham P, et al.

Asian Pac J Allergy Immunol, 2004 Mar;22(1):11-7.
PMID: 15366653

Airway inflammation can be demonstrated by the modem method of sputum induction using ultrasonic nebulizer and hypertonic saline. We studied whether compressed-air nebulizer and isotonic saline which are commonly available and cost less, are as effective in inducing sputum in normal adult subjects as the above mentioned tools. Sixteen subjects underwent weekly sputum induction in the following manner: ultrasonic nebulizer (Medix Sonix 2000, Clement Clarke, UK) using hypertonic saline, ultrasonic nebulizer using isotonic saline, compressed-air nebulizer (BestNeb, Taiwan) using hypertonic saline, and compressed-air nebulizer using isotonic saline. Overall, the use of an ultrasonic nebulizer and hypertonic saline yielded significantly higher total sputum cell counts and a higher percentage of cell viability than compressed-air nebulizers and isotonic saline. With the latter, there was a trend towards squamous cell contaminations. The proportion of various sputum cell types was not significantly different between the groups, and the reproducibility in sputum macrophages and neutrophils was high (Intraclass correlation coefficient, r [95%CI]: 0.65 [0.30-0.91] and 0.58 [0.22-0.89], p < 0.001). Overall changes in median FEV, were small and comparable between all groups. Induction using ultrasonic nebulizers together with hypertonic saline was generally less well tolerated than compressed-air nebulizers and isotonic saline. We conclude that in normal subjects, although both nebulizers and saline types can induce sputum with reproducible cellular profile, ultrasonic nebulizers and hypertonic saline are more effective but less well tolerated.

Matched MeSH terms: Administration, Inhalation
Inhaled endotoxin in healthy human subjects: a dose-related study on systemic effects and peripheral CD4+ and CD8+ T cells

Loh LC, Vyas B, Kanabar V, Kemeny DM, O'Connor BJ

Respir Med, 2006 Mar;100(3):519-28.
PMID: 16039108

Inhaled endotoxin or lipopolysaccharide (LPS) is implicated in the pathogenesis of pulmonary diseases. We investigated the inhalation effects of two different doses of LPS in healthy human subjects.

Matched MeSH terms: Administration, Inhalation
Aerosol-Based Cell Therapy for Treatment of Lung Diseases

Kardia E, Halim NSSA, Yahaya BH

Methods Mol Biol, 2016;1516:243-255.
PMID: 27062596 DOI: 10.1007/7651_2016_327

Aerosol-based cell delivery technique via intratracheal is an effective route for delivering transplant cells directly into the lungs. An aerosol device known as the MicroSprayer(®) Aerosolizer is invented to transform liquid into an aerosol form, which then can be applied via intratracheal administration for drug delivery. The device produces a uniform and concentrated distribution of aerosolized liquid. Using the capability of MicroSprayer(®) Aerosolizer to transform liquid into aerosol form, our group has designed a novel method of cell delivery using an aerosol-based technique. We have successfully delivered skin-derived fibroblast cells and airway epithelial cells into the airway of a rabbit with minimum risk of cell loss and have uniformly distributed the cells into the airway. This chapter illustrates the application of aerosol device to deliver any type of cells for future treatment of lung diseases.

Matched MeSH terms: Administration, Inhalation
Bronchodilator response to inhaled beta-2 agonist and anticholinergic drugs in patients with bronchiectasis

Hassan JA, Saadiah S, Roslan H, Zainudin BM

Respirology, 1999 Dec;4(4):423-6.
PMID: 10612580 DOI: 10.1046/j.1440-1843.1999.00215.x

OBJECTIVE: An increase in incidence of reversible airflow obstruction and bronchial hyperresponsiveness occurs in patients with bronchiectasis. We conducted a study to assess the efficacy of bronchodilators in the treatment of bronchiectasis.
METHODOLOGY: Twenty-four patients with confirmed bronchiectasis were studied. Each patient inhaled fenoterol 400 microg administered by metered dose inhaler via a spacer after a baseline lung function and a lung function test was repeated 30 min later. This was followed by a second dose of fenoterol 5 mg via nebulizer and another lung function test 30 min later. A repeat study was done at least 24 h later with ipratropium bromide 40 microg by metered dose inhaler and 500 microg by a nebulizer.
RESULTS: The results showed a significant improvement from baselines (mean percentage change +/- SD) of peak expiratory flow rate (PEF) by 8.5 +/- 8.72% and 15.3 +/- 11.63%, forced expiratory volume in 1 s (FEV1) by 8.77 +/- 9.69% and 10.2 +/- 12.2% and forced vital capacity (FVC) by 10.25 +/- 11.61% and 10.09 +/- 10.88% after low- and high-dose fenoterol, respectively. The improvements after low- and high-dose ipratropium bromide for PEE FEV1 and FVC were 9.89 +/- 9.35% and 14.39 +/- 12.82%, 9.38 +/- 10.41% and 13.52 +/- 17.09%, and 8.03 +/- 10.85% and 9.63 +/- 13.85%, respectively. Eleven patients (45.8%) responded to one or both bronchodilators significantly (> 15% improvement in FEV1). Five patients (20%) responded to both, three (12%) to fenoterol alone and another three (12%) to ipratropium bromide alone.
CONCLUSION: There is significant bronchodilator response in a subset of patients with bronchiectasis and patients with bronchiectasis should therefore undergo bronchodilator testing. Skin prick testing against a panel of nine allergens done on each individual yielded a positive result in 13 patients (54.2%).

Matched MeSH terms: Administration, Inhalation
Relationship between head growth and neurodevelopmental outcome of Malaysian very low birthweight infants during the 1st year of life

Ong LC, Boo NY, Chandran V, Zamratol SM, Allison L, Teoh SL, et al.

Ann Trop Paediatr, 1997 Sep;17(3):209-16.
PMID: 9425375

A prospective study was carried out to (i) compare head growth patterns of 103 very low birthweight (VLBW, < 1500 g) Malaysian infants and 98 normal birthweight (NBW, 2500- < 4500 g) controls during the 1st year of life; and (ii) examine the relationship between neurodevelopmental outcome at 1 year of age and occipito-frontal head circumferences (OFC) at birth and at 1 year of age in VLBW babies. When compared with those of NBW infants at birth, mid-infancy and 1 year of age, the mean OFC ratios (observed/expected OFC at 50th percentile) of VLBW infants were significantly lower (p < 0.001). Small-for-gestational-age (SGA) VLBW babies had significantly lower mean OFC ratios than their appropriate-for-gestational-age (AGA) VLBW counterparts at birth (p < 0.001), but this difference was no longer seen at mid-infancy or at 1 year of age. Logistic regression analysis showed that abnormal late neonatal cranial ultrasound findings (odds ratio 8.5, 95% confidence interval 4.12-22.07; p < 0.001) and each additional day of oxygen therapy (odds ratio 1.15, 95% confidence interval 1.00-4.45; p = 0.045) were significant risk factors associated with neurodevelopmental disability at 1 year of age, while mean OFC ratios at birth or at 1 year of age were not. Poor postnatal head growth per se did not predict disability, but probably reflected the consequences of "brain injury" as evidenced by abnormal brain scans.

Matched MeSH terms: Oxygen Inhalation Therapy
Upward transtentorial herniation of posterior fossa structures

Wang CY, Chee CP, Delilkan AE

Eur J Anaesthesiol, 1991 Nov;8(6):469-70.
PMID: 1765045
Matched MeSH terms: Anesthesia, Inhalation
Fulltext Clinical profile and outcomes of asymptomatic vs. symptomatic travellers diagnosed with COVID-19: An observational study from a coastal town in South India

Gupta N, John A, Kokkottil MS, Varma M, Umakanth S, Saravu K

Drug Discov Ther, 2021 Mar 10;15(1):1-8.
PMID: 33642450 DOI: 10.5582/ddt.2020.03068

Despite the high number of coronavirus disease-19 (COVID-19) cases from India, there are few reports from India describing the clinical epidemiology of COVID-19. This study aimed to describe the clinical/epidemiological characteristics and outcomes of asymptomatic vs. symptomatic COVID-19 patients. This was a retrospective chart review of all admitted patients with COVID-19 above 18 years with a history of travel within one month of the admission. The patients were categorized into asymptomatic and symptomatic. The symptomatic patients were further classified into mild, moderate and severe. The demographic profile, risk factors, clinical features, laboratory parameters, treatment details and outcome of all patients were recorded. The clinical and laboratory parameters were compared between symptomatic patients and asymptomatic patients. Of the 127 recruited patients, 75 were asymptomatic. Of the 52 symptomatic patients, 41 patients were classified as a mild illness. The mean age of the patients was 44.5 ± 15 years. A total of 73 patients had one or more risk factors. The male patients were more commonly found to be symptomatic compared to female patients. Neutrophil-lymphocyte ratio, C-reactive protein and lactate dehydrogenase were significantly elevated in symptomatic patients. A total of five individuals required supplemental oxygen therapy, and one of them required mechanical ventilation. All the patients had favourable outcomes. Asymptomatic and mild illness form a significant proportion of positive patients and have excellent outcomes without therapeutic interventions.

Matched MeSH terms: Oxygen Inhalation Therapy
Fulltext Occupational and Environmental Risk Factors Influencing the Inducement of Erythema among Nigerian Laboratory University Workers with Multiple Chemical Exposures

Reuben U, Ismail AF, Ahmad AL, Maina HM, Daud A

Int J Environ Res Public Health, 2019 04 13;16(8).
PMID: 31013942 DOI: 10.3390/ijerph16081334

: The chemicals from laboratories pose a significant risk forinducing erythema, an abnormal redness of the skin, as a result of poor occupational and environmental factors that promote hypersensitivity to a chemical agent. The aim of this present study was to determine the occupational and environmental risk factors influencing the inducement of erythema in laboratory workers due to exposure to chemicals. This was a cross-sectional study on a population-based sample of Nigerian university laboratory workers. Data were collected using the erythema index meter and an indoor air control meter. The study included 287 laboratory workers. The laboratory workers who properly used personal protective equipment (PPE) were 60% less likely to have induced erythema (adjusted odds ratio (AOR) = 0.40; 95% confidence interval CI: 0.22-0.77; probability value p = 0.011). The chemical mixture exceeding the permissible exposure limit (PEL) was found to have a small effect in inducing the erythema (AOR = 4.22; 95%CI: 2.88-12.11; p = 0.004). Most of the sampled laboratories where the respondents worked had unsuitable temperatures (AOR = 8.21; 95% CI: 4.03-15.01; p = 0.001). Erythema was more frequently found in the respondents who spent 4-5h in the laboratory (AOR = 3.11; 95%CI: 1.77-9.23; p = 0.001). However, high levels of ventilation reduce the likelihood of erythema in a laboratory by 82% (0.18). Multiple logistic regressions revealed that PPE, PEL, exposure time, temperature, and ventilation were the probable predictive factors associated with the inducement of erythema. Providing better educational knowledge and improving the attitude towards hazards and safety in a laboratory would lead to reduced rates of new cases.

Matched MeSH terms: Inhalation Exposure
Lipid-based pulmonary delivery system: a review and future considerations of formulation strategies and limitations

Ngan CL, Asmawi AA

Drug Deliv Transl Res, 2018 10;8(5):1527-1544.
PMID: 29881970 DOI: 10.1007/s13346-018-0550-4

Inhalation therapy of lipid-based carriers has great potential in direct target towards the root of respiratory diseases, which make them superior over other drug deliveries. With the successful entry of lipid carriers into the target cells, drugs can be absorbed in a sustained release manner and yield extended medicinal effects. Nevertheless, translation of inhalation therapy from laboratory to clinic especially in drug delivery remains a key challenge to the formulators. An ideal drug vehicle should safeguard the drugs from any premature elimination, facilitate cellular uptake, and promote maximum drug absorption with negligible toxicity. Despite knowing that lung treatment can be done via systemic delivery, pulmonary administration is capable of enhancing drug retention within the lungs, while minimizing systemic toxicity with local targeting. Current inhalation therapy of lipid-based carriers can be administered either intratracheally or intranasally to reach deep lung. However, the complex dimensions of lung architectural and natural defense mechanism poise major barriers towards targeted pulmonary delivery. Delivery systems have to be engineered in a way to tackle various diseases according to their biological conditions. This review highlights on the developmental considerations of lipid-based delivery systems cater for the pulmonary intervention of different lung illnesses.

Matched MeSH terms: Administration, Inhalation
The potential to treat lung cancer via inhalation of repurposed drugs

Lee WH, Loo CY, Ghadiri M, Leong CR, Young PM, Traini D

Adv Drug Deliv Rev, 2018 08;133:107-130.
PMID: 30189271 DOI: 10.1016/j.addr.2018.08.012

Lung cancer is a highly invasive and prevalent disease with ineffective first-line treatment and remains the leading cause of cancer death in men and women. Despite the improvements in diagnosis and therapy, the prognosis and outcome of lung cancer patients is still poor. This could be associated with the lack of effective first-line oncology drugs, formation of resistant tumors and non-optimal administration route. Therefore, the repurposing of existing drugs currently used for different indications and the introduction of a different method of drug administration could be investigated as an alternative to improve lung cancer therapy. This review describes the rationale and development of repositioning of drugs for lung cancer treatment with emphasis on inhalation. The review includes the current progress of repurposing non-cancer drugs, as well as current chemotherapeutics for lung malignancies via inhalation. Several potential non-cancer drugs such as statins, itraconazole and clarithromycin, that have demonstrated preclinical anti-cancer activity, are also presented. Furthermore, the potential challenges and limitations that might hamper the clinical translation of repurposed oncology drugs are described.

Matched MeSH terms: Administration, Inhalation
Protein and peptide delivery to lungs by using advanced targeted drug delivery

Chellappan DK, Prasher P, Saravanan V, Vern Yee VS, Wen Chi WC, Wong JW, et al.

Chem Biol Interact, 2022 Jan 05;351:109706.
PMID: 34662570 DOI: 10.1016/j.cbi.2021.109706

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.

Matched MeSH terms: Administration, Inhalation
Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment

Shah K, Chan LW, Wong TW

Drug Deliv, 2017 Nov;24(1):1631-1647.
PMID: 29063794 DOI: 10.1080/10717544.2017.1384298

The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.

Matched MeSH terms: Administration, Inhalation

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