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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, Intranasal
Nose to Brain Delivery of Nanocarriers Towards Attenuation of Demented Condition

Gorain B, Rajeswary DC, Pandey M, Kesharwani P, Kumbhar SA, Choudhury H

Curr Pharm Des, 2020;26(19):2233-2246.
PMID: 32167424 DOI: 10.2174/1381612826666200313125613

Increasing incidence of demented patients around the globe with limited FDA approved conventional therapies requires pronounced research attention for the management of the demented conditions in the growing elderly population in the developing world. Dementia of Alzheimer's type is a neurodegenerative disorder, where conventional therapies are available for symptomatic treatment of the disease but possess several peripheral toxicities due to lack of brain targeting. Nanotechnology based formulations via intranasal (IN) routes of administration have shown to improve therapeutic efficacy of several therapeutics via circumventing blood-brain barrier and limited peripheral exposure. Instead of numerous research on polymeric and lipid-based nanocarriers in the improvement of therapeutic chemicals and peptides in preclinical research, a step towards clinical studies still requires wide-ranging data on safety and efficacy. This review has focused on current approaches of nanocarrierbased therapies on Alzheimer's disease (AD) via the IN route for polymeric and lipid-based nanocarriers for the improvement of therapeutic efficacy and safety. Moreover, the clinical application of IN nanocarrier-based delivery of therapeutics to the brain needs a long run; however, proper attention towards AD therapy via this platform could bring a new era for the AD patients.

Matched MeSH terms: Administration, Intranasal
Inflammation and oxidative stress impair preimplantation embryonic morphogenesis in allergic asthma model

Wafriy CI, Kamsani YS, Nor-Ashikin MNK

Cells Dev, 2023 Sep;175:203864.
PMID: 37321350 DOI: 10.1016/j.cdev.2023.203864

The incidence of allergic asthma has been increasing worldwide in recent decades. Also, an increasing number of women are suffering from poor pregnancy outcome. However, the causal relationship between allergic asthma and embryonic growth in terms of cell morphogenesis has not been well elucidated. Here, we investigated the impact of allergic asthma on the morphogenesis of preimplantation embryos. Twenty-four female BALB/c were randomly divided into control (PBS), 50-μg (OVA1), 100-μg (OVA2) and 150-μg (OVA3). On Days-0 and -14, mice were induced intraperitoneally (i.p) with ovalbumin (OVA). On Days-21 until -23, mice were challenged with OVA via intranasal instillation (i.n). Control animals were sensitized and challenged with PBS. At the end of treatment (Day-25), 2-cell embryos were retrieved and cultured in vitro until the blastocysts hatched. Results showed reduced number of preimplantation embryos at all developing stages in all treated groups (p ≤ 0.0001). Uneven blastomere size, partial compaction- and cavitation-activity, low formation of trophectoderm (TE), as well as cell fragmentation were noted in all the treated groups. Maternal serum interleukin (IL)-4, immunoglobulin (Ig)-E and 8-hydroxydeoxyguanosine (8-OHdG) were notably high (p ≤ 0.0001, p ≤ 0.01) in contrast with low total antioxidant capacity (TAOC) (p ≤ 0.0001). Our findings indicated that OVA-induced allergic asthma had compromised cell morphogenesis through reduced blastomere cleavage division, partial compaction and cavitation-activity, impairment of TE production, and cell fragmentation leading to embryonic cell death via OS mechanism.

Matched MeSH terms: Administration, Intranasal
Fulltext Salted fish and inhalants as risk factors for nasopharyngeal carcinoma in Malaysian Chinese

Armstrong RW, Armstrong MJ, Yu MC, Henderson BE

Cancer Res, 1983 Jun;43(6):2967-70.
PMID: 6850606

We conducted a case-control study of nasopharyngeal carcinoma among Malaysian Chinese to test inhalants, salted fish consumption, and use of tobacco, alcohol, and nasal ointments as risk factors for the disease. Interviews with 100 cases and 100 controls indicated that salted fish consumption during childhood was a significant risk factor (relative risk, 3.0; p = 0.04); childhood daily consumption of this food item compared to nonconsumption carried a relative risk of 17.4 [95% confidence interval = (2.7, 111.1)]. Occupational exposure to smokes (relative risk, 6.0; p = 0.006) and to dusts (relative risk, 4.0; p less than 0.001) was also significantly associated with nasopharyngeal carcinoma. The two risk factors (consumption of salted fish and exposure to smoke and/or dust) were independent of each other. There was no association between nasopharyngeal carcinoma and tobacco, alcohol, or nasal ointments.

Matched MeSH terms: Administration, Intranasal/adverse effects
Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches

Bhattamisra SK, Shin LY, Saad HIBM, Rao V, Candasamy M, Pandey M, et al.

CNS Neurol Disord Drug Targets, 2020;19(3):174-183.
PMID: 32418534 DOI: 10.2174/1871527319666200518102130

The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords "insulin"; "insulin resistance"; "Alzheimer's disease"; "Parkinson's disease" in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.

Matched MeSH terms: Administration, Intranasal
Nanoparticles Based Intranasal Delivery of Drug to Treat Alzheimer's Disease: A Recent Update

Pandey M, Choudhury H, Verma RK, Chawla V, Bhattamisra SK, Gorain B, et al.

CNS Neurol Disord Drug Targets, 2020;19(9):648-662.
PMID: 32819251 DOI: 10.2174/1871527319999200819095620

Alzheimer Association Report (2019) stated that the 6th primary cause of death in the USA is Alzheimer's Disease (AD), which leads to behaviour and cognitive impairment. Nearly 5.8 million peoples of all ages in the USA have suffered from this disease, including 5.6 million elderly populations. The statistics of the progression of this disease is similar to the global scenario. Still, the treatment of AD is limited to a few conventional oral drugs, which often fail to deliver an adequate amount of the drug in the brain. The reduction in the therapeutic efficacy of an anti-AD drug is due to poor solubility, existence to the blood-brain barrier and low permeability. In this context, nasal drug delivery emerges as a promising route for the delivery of large and small molecular drugs for the treatment of AD. This promising pathway delivers the drug directly into the brain via an olfactory route, which leads to the low systemic side effect, enhanced bioavailability, and higher therapeutic efficacy. However, few setbacks, such as mucociliary clearance and poor drug mucosal permeation, limit its translation from the laboratory to the clinic. The above stated limitation could be overcome by the adaption of nanoparticle as a drug delivery carrier, which may lead to prolong delivery of drugs with better permeability and high efficacy. This review highlights the latest work on the development of promising Nanoparticles (NPs) via the intranasal route for the treatment of AD. Additionally, the current update in this article will draw the attention of the researcher working on these fields and facing challenges in practical applicability.

Matched MeSH terms: Administration, Intranasal
Reflections on: Pharmacokinetics of Intranasal Dexmedetomidine

Sethuraman RM, Suresh V

Anesth Analg, 2023 Aug 01;137(2):e19.
PMID: 37450919 DOI: 10.1213/ANE.0000000000006581
Matched MeSH terms: Administration, Intranasal
Fulltext Mometasone furoate intranasal spray is effective in reducing symptoms and adenoid size in children and adolescents with adenoid hypertrophy

Ghafar MHA, Mohamed H, Mohammad NMY, Mohammad ZW, Madiadipoera T, Wang Y, et al.

Acta Otorrinolaringol Esp (Engl Ed), 2019 08 07;71(3):147-153.
PMID: 31400807 DOI: 10.1016/j.otorri.2019.04.004

INTRODUCTION: The use of mometasone furoate (MF) intranasal spray in treating adenoid hypertrophy (AH) has a variable outcome due the different methods of adenoid size evaluation. The aim of our study was to evaluate the effect of MF intranasal spray in children and adolescents with AH using a reliable and consistent endoscopic evaluation.
MATERIAL AND METHOD: A prospective interventional study was conducted. Evaluation took place during the first visit (week 0) and second visit (week 12). Symptoms of nasal obstruction, rhinorrhoea, cough and snoring were assessed, and an overall total symptoms score was obtained. A rigid nasoendoscopic examination using a four-grading system of adenoid size from 1 to 4 was performed. Patients were treated with MF intranasal spray for 12 weeks. Patients' aged 7-11-years old used 1 spray in each nostril once daily, while patients aged 12-17 used two sprays in each nostril once daily. Reassessment was carried out during the second visit (week 12).
RESULTS: A total of 74 patients was recruited. There were significant improvements from week 0 to week 12 in the symptoms' score for nose obstruction, rhinorrhoea, cough, snoring including the total nasal symptoms' score (p<0.001). AH significantly reduced in size from week 0 (2.89±.87) to week 12 (1.88±.83) (p<0.001).
CONCLUSION: MF intranasal spray is effective in improving the symptoms attributed to AH as well as reducing the adenoid size. MF intranasal spray is advocated as a treatment option before adenoidectomy is considered.

Matched MeSH terms: Administration, Intranasal