Lung inflammation involves the activation of immune cells and inflammatory mediators in response to injury and infection. When inflammation persists, fibroblasts, which are resident lung cells, become activated, leading to pulmonary fibrosis (PF), abnormal wound healing, and long-term damage to the alveolar epithelium. This persistent inflammation and fibrosis can also elevate the risk of lung cancer, emphasizing the need for innovative treatments. Current therapies, such as inhaled corticosteroids (ICS) and chemotherapy, have significant limitations. Although conventional nanoparticles (NPs) provide a promising avenue for treating lung disorders, they have limited selectivity and stability. Polyethylene glycol (PEG) grafting can prevent NP aggregation and phagocytosis, thus prolonging their circulation time. When combined with targeting ligands, PEGylated NPs can deliver drugs precisely to specific cells or tissues. Moreover, pH-sensitive NPs offer the advantage of selective drug delivery to inflammatory or tumor-acidic environments, reducing side effects. These NPs can change their size, shape, or surface charge in response to pH variations, improving drug delivery efficiency. This review examines the techniques of PEGylation, the polymers used in pH-sensitive NPs, and their therapeutic applications for lung inflammation, fibrosis, and cancer. By harnessing innovative NP technologies, researchers can develop effective therapies for respiratory conditions, addressing unmet medical needs and enhancing patient outcomes.
Pulmonary disease is sometimes treated empirically as tuberculosis (TB) in the absence of microbial confirmation if the clinical suspicion of active TB is high. In a country of relatively high TB and low HIV burden, we retrospectively studied 107 patients (69.2% male; mean age (SD): 45 (17) years) who received empirical anti-TB treatment for intrapulmonary opacities or pleural effusions suspected of active TB in our hospitals between 1998 and 2002. The diagnosis of definite or probable 'smear-negative' pulmonary TB was made based on treatment outcome at two months with rifampicin, isoniazid, pyrazinamide and ethambutol (or streptomycin). At this end-point, 81 patients (84.4%) had both clinical and radiological improvement (definite cases), 12 (12.5%) had clinical improvement alone and 3 (3.1%) had radiological improvement alone (probable cases). Confirmation of acid-fast bacilli was subsequently obtained in 12 patients (all definite cases) from culture of initial pulmonary specimens. Eleven patients (10.5%) were diagnosed as 'non-TB' based on absence of both clinical and radiological improvement or discovery of another cause for the pulmonary condition at or before this two-month study end-point. In the 'non-TB' group, 2 had carcinoma, 2 had HIV-related pulmonary diseases, 1 had bronchiectasis, while in 6 causes were indeterminate. Six (6.3%) and 3 (27.3%) patients reported adverse effects from anti-TB drugs from the 'TB' and 'non-TB' groups respectively. Our findings suggest that empirical anti-TB treatment is an acceptable practice if clinical suspicion is high in patients coming in our region.
A female patient who presented with left empyema thoracis caused by Actinomyces odontolyticus is reported. She responded to treatment with penicillin and metronidazole but after 3 weeks developed leucopenia complicated by gram-negative septicaemia. Leucopenia improved rapidly on withdrawal of metronidazole. Treatment was continued with a prolonged course of penicillin and she made an uneventful recovery.
Introduction: Pulmonary route is one of the preferred routes for the administration of therapeutically active agents for systemic as well as localized delivery. Chronic obstructive pulmonary disease (COPD), bronchial asthma, pneumonia, pulmonary hypertension, bronchiolitis, lung cancer, and tuberculosis are the major chronic diseases associated with the pulmonary system. Knowledge about the affecting factors, namely, the etiology, pathophysiology, and the various barriers (mechanical, chemical, immunological, and behavioral) in pulmonary drug delivery is essential to develop an effective drug delivery system. Formulation strategies and mechanisms of particle deposition in the lungs also play an important role in designing a suitable delivery system.Areas covered: In the present paper, various drug delivery strategies, viz. nanoparticles, microparticles, liposomes, powders, and microemulsions have been discussed systematically, from a patent perspective.Expert opinion: Patent publications on formulation strategies have been instrumental in the evolution of new techniques and technologies for safe and effective treatment of pulmonary diseases. New delivery systems are required to be simple/reproducible/scalable/cost-effective scale for manufacturing ability and should be safe/effective/stable/controllable for meeting quality and regulatory compliance.
Nuclear factor-kappa B, involved in inflammation, host immune response, cell adhesion, growth signals, cell proliferation, cell differentiation, and apoptosis defense, is a dimeric transcription factor. Inflammation is a key component of many common respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and acute respiratory distress syndrome. Many basic transcription factors are found in NF-κB signaling, which is a member of the Rel protein family. Five members of this family c-REL, NF-κB2 (p100/p52), RelA (p65), NF-κB1 (p105/p50), RelB, and RelA (p65) produce 5 transcriptionally active molecules. Proinflammatory cytokines, T lymphocyte, and B lymphocyte cell mitogens, lipopolysaccharides, bacteria, viral proteins, viruses, double-stranded RNA, oxidative stress, physical exertion, various chemotherapeutics are the stimulus responsible for NF-κB activation. NF-κB act as a principal component for several common respiratory illnesses, such as asthma, lung cancer, pulmonary fibrosis, COPD as well as infectious diseases like pneumonia, tuberculosis, COVID-19. Inflammatory lung disease, especially COVID-19, can make NF-κB a key target for drug production.
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.
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.
BACKGROUND: Prescribing medicines in an unlicensed and off-label manner for children is a widespread practice around the world.
OBJECTIVES: To determine the extent and predictors of off-label respiratory drug prescriptions for children in the outpatient clinics of a hospital in Malaysia.
SETTING: Outpatient clinics at the Universiti Kebangsaan Malaysia Medical Centre, a tertiary teaching hospital in Malaysia.
METHODS: The pharmacy-based computer system and medical records of the patients were utilized to collect data from 220 pediatric patients who were prescribed at least one respiratory drug from July 2011 to December 2011.
MAIN OUTCOME MEASURE: Characteristics of the off-label respiratory drug prescriptions were measured.
RESULTS: A total of 134 children (60.9 %) received at least one respiratory drug prescribed in an off-label manner. The most common reasons for the off-label prescribing of drugs were off-label use by indication (31.5 %), followed by higher than the recommended dose (24.9 %) and lower than the recommended frequency (17.1 %). Diphenhydramine was the most common respiratory drug prescribed off-label. The number of medications prescribed was the only significant predictor of off-label prescription of respiratory drugs. Pediatric patients receiving 4-6 medications were 7.8 times more likely to receive at least one off-label respiratory drug compared to pediatric patients that received 1-3 medications (OR 7.8, 95 % CI 1.74-37.44).
CONCLUSION: There was substantial prescribing of respiratory drugs for children in an off-label manner at the outpatient clinics at the Universiti Kebangsaan Malaysia Medical Centre. This highlights the need for more research to be carried out on respiratory drugs in the pediatric population.
Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
A 12-year old girl presented with an unusual problem of recurrent discharging multiple skin sinuses on her right anterior and posterior chest wall for a year. There was ipsilateral lower lobe pneumonia and imaging showed multiple abscesses in her lower back muscles bilaterally. A purulent fluid was aspirated from her back muscles and the histology examination showed sulphur granules with gram positive branched filaments. She responded well to the treatment for actinomycosis with penicillin and doxycycline.
A 30-year-old Chinese lady was admitted for hoarseness of voice of one month's duration. Clinical examination revealed a granuloma of the left vocal cord while chest X-ray showed an opacity in the lower lobe of the right lung. The provisional clinical diagnosis was tuberculous laryngitis. A biopsy of the vocal cord lesion revealed inflamed tissue with actinomycotic colonies. Cultures and sputum smears did not reveal any tuberculous bacilli. The patient responded to a 6-week course of intravenous C-penicillin, regaining her voice on day 5 of commencement of antibiotics. A subsequent CT scan of the neck and thorax revealed multiple non-cavitating nodular lesions in both lung fields, felt to be indicative of resolving actinomycosis. She was discharged well after completion of treatment. It was felt that this is a case of primary actinomycosis of the vocal cord with probably secondary pulmonary actinomycosis.
Fourteen cases of sarcoidosis consisting of 7 male and 7 female patients with a mean age of 42.4 years were seen at the University Hospital from 1972 to 1990. There were 10 Indians, 2 Malays, and 2 Chinese. Twelve patients had thoracic involvement. The other common disease manifestations included weight loss, arthralgia, hepatomegaly, erythema nodosum, peripheral lymphadenopathy, and hypercalcaemia. At initial presentation, the disease was in radiographic stage I, II, and III in 8, 3 and one patient respectively. The Kveim test was positive in 7 out of 9 patients. Eight patients required steroid therapy.