Multiple Routes Of Administration Research Articles

Ketamine for Migraine in the Emergency Department.

Ketamine is utilized often in the emergency department (ED) for rapid sequence intubation, procedural sedation, and acute pain management. The treatment of migraine headache in the ED varies widely and is dependent on several factors including migraine cause, previous successful abortive methods, and provider preference. Several medications are currently employed to treat acute migraine including nonsteroidal anti-inflammatory drugs, triptans, antihistamines, prochlorperazine, and corticosteroids, among others. Interest in ketamine as an abortive agent to treat migraine has increased as evidenced by recent studies evaluating its use in the ED. This review examines the data regarding the use of ketamine to treat migraine headache. The concept of treating migraine headache with ketamine has been studied for more than 20 years. Early studies conducted primarily in the outpatient setting evaluated ketamine through multiple routes of administration and differing migraine causes with varying results. These early data seem to suggest that ketamine provides relief from headache severity but provides little information regarding the optimal dose and route of administration. Recent active comparator and placebo-controlled trials in the ED utilizing subdissociative doses of ketamine (0.2-0.3 mg/kg intravenously) show conflicting results. To confound the decision regarding its use further, ED providers encounter differing recommendations regarding its place in therapy. Current data suggest that ketamine may provide pain relief to patients with migraine headache. Although there may be a role for ketamine in certain cases after more robust evidence becomes available, currently it is premature to incorporate ketamine into routine use. Several questions remain to be answered including its overall efficacy, place in therapy, dosage, and risk of undesirable side effects.

Preclinical Toxicology of rQNestin34.5v.2: An Oncolytic Herpes Virus with Transcriptional Regulation of the ICP34.5 Neurovirulence Gene

rQNestin34.5v.2 is an oncolytic herpes simplex virus 1 (oHSV) that retains expression of the neurovirulent ICP34.5 gene under glioma-selective transcriptional regulation. To prepare an investigational new drug (IND) application, we performed toxicology and efficacy studies of rQNestin34.5v.2 in mice in the presence or absence of the immunomodulating drug cyclophosphamide (CPA). ICP34.5 allows HSV1 to survive interferon and improves viral replication by dephosphorylation of the eIF-2α translation factor. rQNestin34.5v.2 dephosphorylated eIF-2α in human glioma cells, but not in human normal cells, resulting in significantly higher cytotoxicity and viral replication in the former compared to the latter. In vivo toxicity of rQNestin34.5v.2 was compared with that of wild-type F strain in immunocompetent BALB/c mice and athymic mice by multiple routes of administration in the presence or absence of CPA. A likely no observed adverse effect level (NOAEL) dose for intracranial rQNestin34.5v.2 was estimated, justifying a phase 1 clinical trial in recurrent glioma patients (ClinicalTrials.gov: NCT03152318), after successful submission of an IND.

SEDATIVE, CARDIORESPIRATORY, AND THERMOREGULATORY EFFECTS OF ALFAXALONE ON BUDGERIGARS (MELOPSITTACUS UNDULATUS).

Alfaxalone is a neurosteroid anesthetic agent that has been extensively used in both human and veterinary medicine for more than 50 yr. Previous studies involving avian species demonstrated various dose ranges and multiple routes of administration. The aim of this study was to evaluate the short-term sedative, cardiorespiratory, and thermoregulatory effects of an intramuscular injection of alfaxalone on budgerigars (Melopsittacus undulatus). A crossover study was performed with a sample size of 10 male budgerigars, previously determined to be healthy based on physical examination. Alfaxalone was administered intramuscularly at two doses: 15 and 20 mg/kg. The lower dose resulted in mild to moderate sedation for 29 ± 5 min, whereas the higher dose resulted in moderate to profound sedation for 29 ± 7 min. A statistically significant decrease in heart rate was observed 2 min after administration of alfaxalone at 15 mg/kg; however, this finding was noted to be transient. A statistically significant decrease in respiratory rate was observed at 6 and 10 min after injection in both groups. Cloacal temperature measurement with a digital thermometer and eye temperature calculated from thermographic images demonstrated a decrease in body temperature over time but was not found to be statistically significant. Intramuscular use of alfaxalone proved to provide short-term sedation in budgerigars, with statistically significant but clinically mild cardiorespiratory effects. Due to a significant decrease in body temperature, active warming is recommended when using alfaxalone in budgerigars.

To Infinity and Beyond: Developing a Nursing Cellular Therapy Program of Care

Topic Significance & Study Purpose/Background/Rationale For nurses to be proficient in caring for patients with cellular treatment protocols, the need for a formal, standardized educational program and practice standards for nursing care is critical. The use of cellular therapy is growing beyond standard of care for malignancy and hematologic disease. Cellular therapy administration in multiple clinical care settings makes it difficult to ensure all nurses have the same level of knowledge and practice which could result in gaps of care for patients. Researchers are actively investigating adoptive cell transfer including Tumor Infiltrating Cells, Dendritic Cells, Chimeric Antigen Receptor T-Cells, as well as other cellular therapies. The need for a formalized Cellular Therapy Program of Care was identified to standardize education and practice for nurses within the oncology, transplant, medical surgical, ambulatory, pediatric, and intensive care specialties. Methods, Intervention, & Analysis Trends in approved therapies as well as new research protocols show an increase in use of cellular therapies. Additionally, application of cellular therapy has expanded to diseases other than cancer and encompasses multiple routes of administration, e.g. intradermal, intraperitoneal, and intrathecal. Nursing programs of care that have not traditionally administered cellular products may begin to implement these treatments. Findings & Interpretation A multi-disciplinary team developed a standardized approach for education and practice that includes; education in cellular science and chemotherapy, standards of practice and procedures on cellular administration, training in complications of cellular medicine, competency assessment, and standardized documentation practices Discussion & Implications The Nursing Cellular Therapy Program of Care is in its early stages and outcome evaluation will be measured through patient quality indicators, documentation compliance, and ongoing competency evaluation. Formalization of a cellular program standardizes nursing practice and ensures patient safety.

Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science.

Molecular hydrogen (H2) is a colorless, tasteless, odorless, and minimal molecule with high flammability. Although H2 has been thought to be an inert gas in living bodies for many years, an animal study reported that inhalation of H2 gas decreased oxidative stress and suppressed brain injury caused by ischemia and reperfusion injury due to its antioxidant action. Since then, the antioxidant action of H2 has attracted considerable attention and many studies have reported on its benefits. Most studies have reported the effects of H2 on diseases such as cancer, diabetes, cerebral infarction, and Alzheimer's disease. However, little is known regarding its effects on healthy subjects and exercise. Thus far, including our study, only 6 studies have explored the effect of H2 on exercise. H2 is the smallest molecule and therefore can easily penetrate the cellular membrane and rapidly diffuse into organelles. H2 is thought to be able to selectively reduce hydroxyl radicals and peroxynitrite and does not affect physiologically reactive species. H2 can be supplied to the body through multiple routes of administration, such as oral intake of H2 water and H2 bathing. Therefore, H2 may be a potential alternative strategy for conventional exogenous antioxidant interventions in sports science. The purpose of this review is to provide evidence regarding the effects of H2 intake on changes in physiological and biochemical parameters, centering on exercise-induced oxidative stress, for each intake method. Furthermore, this review highlights possible future directions in this area of research.

Evaluating different routes of extracellular vesicle administration for cranial therapies.

Aim:Human stem cell-derived extracellular vesicles (EV) provide many advantages over cell-based therapies for the treatment of functionally compromised tissue beds and organ sites. Here we aimed to highlight multiple administration routes for the potential treatment of various forms of brain injury.Methods:Human neural stem cell-derived EV were isolated from conditioned media and administered via three distinct routes: intrahippocampal transplantation, retro-orbital vein injection, and intranasal. EV were administered after which brains were evaluated to determine the capability of EV to translocate into normal tissue.Results:Data showed no significant differences in the amount of EV able to translocate across the brain, indicating the functional equivalence of each administration route to effectively deliver EV to the brain parenchyma.Conclusion:Findings show that both systemic administration routes (retro-orbital vein or intranasal delivery) afforded effective penetrance and perfusion of EV throughout the brain in a minimally invasive manner, and point to a translationally tractable option for treating certain neurological disorders including those resulting from cranial irradiation procedures.

Methadone – demystifying an old pain killer

Methadone is a µ-opioid receptor agonist and NMDA recep­tor antagonist which is often indicated for the management of severe refractory cancer or non-cancer pain, as well as for opioid addiction. This two-part article provides an overview of methadone use in pain management, and its use in opioid addiction will not be covered here. Metha­done has several advantages over other opioids. These ad­van­ta­ges include extended analgesic activity, multiple routes of administration, longer bioavailability, lack of ac­tive metabolites, predominantly intestinal excretion, and its relatively low cost compared to other opioids. This makes methadone an appealing option for patients with impaired creatinine clearance and for those facing finan­cial constraints in obtaining medications. On the other hand, there are notable concerns with this medication that make its use more complex than of other opioids. Metha­done has a variable individual plasma half-life that can lead to ac­cu­mu­lation and toxicity, and extensively utilizes cyto­chrome CYP450, therefore its metabolism can be affected when used in conjunction with inducers and especially in­hi­bi­tors of this cytochrome system. Methadone has also variable and quite complicated conversion formulas when transitioning from other opioids. Additionally, there is a risk for abuse that can lead to accidental overdose or even death. Finally, metha­done can cause QT interval pro­lon­ga­tion that may result in dangerous cardiac arrhythmias such as torsades de points and ventricular tachyarrhythmia. Des­pite its mul­­ti­­ple advantages in pain control, cautionary mes­sages from the European Association for Palliative Care (EAPC) and Na­­tio­­nal Comprehensive Cancer Network (NCCN) ad­vise for use of methadone only by experienced clinicians. It is highly re­­com­­mended that patients are counseled exten­sively on me­tha­­done safety use due to its numerous risks.

Current and Emerging Therapeutics for the Management of Endometriosis.

Endometriosis is a chronic benign disease that affects women of reproductive age. Medical therapy is often the first line of management for women with endometriosis in order to ameliorate symptoms or to prevent post-surgical disease recurrence. Currently, there are several medical options for the management of patients with endometriosis. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of chronic inflammatory conditions, being efficacious in relieving primary dysmenorrhea. Combined oral contraceptives (COCs) and progestins, available for multiple routes of administration, are effective first-line hormonal options. In fact, several randomized controlled trials (RCTs) demonstrated that they succeed in improving pain symptoms in the majority of patients, are well tolerated and not expensive. Second-line therapy is represented by gonadotropin-releasing hormone (GnRH) agonists. Even if these drugs are efficacious in treating women not responding to COCs or progestins, they are not orally available and have a less favorable tolerability profile (needing an appropriate add-back therapy). The use of danazol is limited by the large availability of other better-tolerated hormonal drugs. Because few data are available on long-term efficacy and safety of aromatase inhibitors they should be administered only in women with symptoms refractory to other conventional therapies in a clinical research setting. Promising preliminary data have emerged from multicenter Phase III trials on elagolix, a new oral GnRH antagonist but non-inferiority RCT data are required to compare elagolix with first-line therapies for endometriosis.

Ocular Drug Delivery Barriers-Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases.

Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.

Development of a multiroute physiologically based pharmacokinetic model for orbifloxacin in rabbits.

To predict the orbifloxacin concentrations in rabbits after multiple routes of administration, a flow-limited multiroute physiologically based pharmacokinetic (PBPK) model was developed. Three routes of administration (IV, IM, and PO) were incorporated into this model. Physiological parameters including tissue weights and blood flows through different tissues were obtained from the literature. The tissue/plasma partition coefficients (PX s) for noneliminating tissues were calculated according to the area method, while the PX s for kidney and the rest of the body compartment, together with other parameters for absorption and elimination, were optimized based on the published concentrations. The comparisons between predicted and observed orbifloxacin concentrations proved its validity, and the present model predicted available concentration data well, including those in liver, kidney, muscle, lung, heart, and plasma after oral, intravenous, or intramuscular administration. A local sensitivity analysis was also performed, which showed that the parameters for oral absorption were most influential on the orbifloxacin concentrations. This model was used to predict plasma and tissue concentrations after multiple oral or intramuscular administration. This study demonstrated the feasibility of predicting drug residues in minor species after multiple routes of administration in the extra-label manner using the PBPK modeling.

The fentanyl family: A distinguished medical history tainted by abuse.

Beginning in the 1950s, a family of potent opioids was synthesized and developed (fentanyl and analogues). They continue to serve as valuable analgesic agents. But the recent spike and notoriety of their abuse has raised alarm, even calls for tighter control. We review the trajectory of these compounds. To rectify shortcomings of the then available opioid analgesics, an analogue family of compounds was synthesized having a piperidine ring (presumptive principal active moiety in morphine and meperidine). The result was more potent and rapid-acting compounds, including alfentanil, carfentanil, fentanyl, sufentanil and others. These properties, plus availability in formulations for multiple routes of administration, impart broad therapeutic utility. They also unfortunately favour abuse. The abuse of fentanyl and its analogues (legal and illicit) serves as a case study for the dilemma and difficulties balancing a medical need against psychosocial realities. The fentanyl family provides relief for severe pain, but their very properties also engender abuse.

Oral Agents for the Management of Agitation and Agitated Delirium in Critically Ill Patients.

Agitation is one of the most common issues that critically ill patients experience. Medications used to manage agitation are often administered intravenously or intramuscularly in the acutely agitated, critically ill patient. However, a multimodal approach that utilizes multiple routes of administration may be appropriate. This review summarizes the available literature on oral antipsychotics, clonidine, and valproic acid to manage agitation in critically ill patients while also focusing on their pharmacology and appropriate monitoring. Despite inconclusive findings from different studies, antipsychotics, clonidine, and valproic acid may provide benefit for specific patient populations. As more evidence emerges, these agents may start playing a greater role in the management of agitation, which is not amenable to first-line agents. As health care professionals, it is prudent to be familiar with their dosing regimens, common adverse effects, and the monitoring required to maximize patient benefits and minimize harms.

RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions.

RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs. Particularly with ASOs, recent clinical data have demonstrated proof of mechanism and clinical benefit with these approaches across several nononcology disease areas by multiple routes of administration. In cancer, next-generation ASOs have recently demonstrated single-agent activity in patients with highly refractory cancers. Here we discuss advances in RNA therapeutics for the treatment of cancer and the challenges that remain to solidify these as mainstay therapeutic modalities to bridge the pharmacogenomic divide that remains in cancer drug discovery.

Acute kidney injury and critical limb ischaemia associated with the use of the so called "legal high" 3-fluorophenmetrazine.

Until the law in the United Kingdom (UK) changed in May 2016 so called "legal highs" or "new psychoactive substances" were freely available in high street shops across the UK. Following prohibition these drugs are still easily purchased illegally via the internet. We report a case of a patient who self-administered 3-fluorophenmetrazine intravenously with catastrophic consequences. Adverse effects were almost immediate with symptoms of malaise and tachycardia. Two days post administration he was transferred to the intensive therapy unit with acute kidney injury and irreversible four limb ischaemia. He required a period of renal replacement therapy and bilateral lower limb amputation. This case highlights the fact that new psychoactive substances have many unintended adverse effect which have not been previously described. Multiple routes of administration are used by people taking these agents including intravenously. Medical practitioners should always consider ingestion of new psychoactive substances in the differential diagnosis of acutely ill patients.

Subjective and physiological effects, and expired carbon monoxide concentrations in frequent and occasional cannabis smokers following smoked, vaporized, and oral cannabis administration

BackgroundAlthough smoking is the most common cannabis administration route, vaporization and consumption of cannabis edibles are common. Few studies directly compare cannabis’ subjective and physiological effects following multiple administration routes. MethodsSubjective and physiological effects, and expired carbon monoxide (CO) were evaluated in frequent and occasional cannabis users following placebo (0.001% Δ9-tetrahydrocannabinol [THC]), smoked, vaporized, and oral cannabis (6.9% THC, ∼54mg). ResultsParticipants’ subjective ratings were significantly elevated compared to placebo after smoking and vaporization, while only occasional smokers’ ratings were significantly elevated compared to placebo after oral dosing. Frequent smokers’ maximum ratings were significantly different between inhaled and oral routes, while no differences in occasional smokers’ maximum ratings between active routes were observed. Additionally, heart rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization (10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were significantly greater than changes after placebo, with no differences between frequent and occasional smokers. Finally, smoking produced significantly increased expired CO concentrations 0.25–6h post-dose compared to vaporization. ConclusionsAll participants had significant elevations in subjective effects after smoking and vaporization, but only occasional smokers after oral cannabis, indicating partial tolerance to subjective effects with frequent exposure. There were no differences in occasional smokers’ maximum subjective ratings across the three active administration routes. Vaporized cannabis is an attractive alternative for medicinal administrations over smoking or oral routes; effects occur quickly and doses can be titrated with minimal CO exposure. These results have strong implications for safety and abuse liability assessments.

Opportunities and Challenges for Niosomes as Drug Delivery Systems.

With the increase in drug resistance observed in most infectious diseases as well as some forms of cancer, and with the chances of development of new drug molecules to address this issue looking bleak, one of the most plausible ways to disease treatment is combination therapy. Combination therapy would ensure delay in drug resistance, if utilized rationally. However, the biggest difficulty in employing combination therapy are adverse effects due to potential drug-drug interactions and patient compliance due to multiple routes of administration or multiple dosing that may be required. To overcome these issues, researchers have utilized nanoparticle-based systems that can hold multiple drugs in a single carrier. There are several nanocarrier systems available for such purposes. However, the focus of this review will be non-ionic surfactant-based systems (niosomes) for delivery of multiple therapeutic agents. Niosomes are artificially prepared drug delivery carriers. They are structurally similar to liposomes albeit more stable than them. Literature pertaining to combination drug delivery and various drug delivery systems was reviewed. It was conceptualized that many of the methods used to prepare various types of carriers for combination delivery of drugs may be used for niosomal systems as well. We envisage that niosomes may effectively be utilized to package older drugs in newer ways. The review will thus focus on techniques that may be used for the formulation of niosomes, ways to encapsulate multiple-drug moieties, and challenges associated in preparing and optimizing such systems.

Intra uterine extra-amniotic versus vaginal misoprostol for termination of second trimester miscarriage: A randomized controlled trial

Termination of pregnancy in the second trimester using prostaglandins has been shown to be safe and effective. Misoprostol has multiple routes of administration; oral, vaginal, buccal, rectal and sublingual. The study aims to compare the efficacy and safety of intrauterine extra-amniotic and vaginal misoprostol in a dose of 200 microgram every 4 hours for the termination of pregnancy in cases of second trimester miscarriage. A prospective randomized open labeled clinical trial included 180 women with missed miscarriage in gestational age between 13 and 24 wks. Patients were randomized to receive subsequent doses of 200 µg misoprostol every 4 hrs either intra uterine extra-amniotic by Foley catheter or vaginally administered. Randomization was completed using a computer-generated random table. The primary outcome of this study was the mean duration from the initial misoprostol dose until complete fetal expulsion (induction-expulsion interval). The mean gestational age was 17.74 wks. The mean time to complete miscarriage in the intra uterine extra-amniotic group was 5.27 hrs, which was significantly lower than the vaginal group (9.92 hrs, p=0.001). Side effects were more common in vaginal group. Intra uterine extra-amniotic misoprostol with a dose of 200 µg every 4 hrs appears to be more effective and safer than vaginal misoprostol in induction of second trimester miscarriage.

Hyaluronic Acid Molecular Weight Determines Lung Clearance and Biodistribution after Instillation

Hyaluronic acid (HA) has emerged as a versatile polymer for drug delivery. Multiple commercial products utilize HA, it can be obtained in a variety of molecular weights, and it offers chemical handles for cross-linkers, drugs, or imaging agents. Previous studies have investigated multiple administration routes, but the absorption, biodistribution, and pharmacokinetics of HA after delivery to the lung is relatively unknown. Here, pharmacokinetic parameters were investigated by delivering different molecular weights of HA (between 7 and 741 kDa) to the lungs of mice. HA was labeled with either a near-infrared dye or with iodine-125 conjugated to HA using a tyrosine linker. In initial studies, dye-labeled HA was instilled into the lungs and fluorescent images of organs were collected at 1, 8, and 24 h post administration. Data suggested longer lung persistence of higher molecular weight HA, but signal diminished for all molecular weights at 8 h. To better quantitate pharmacokinetic parameters, different molecular weights of iodine-125 labeled HA were instilled and organ radioactivity was determined after 1, 2, 4, 6, and 8 h. The data showed that, after instillation, the lungs contained the highest levels of HA, as expected, followed by the gastrointestinal tract. Smaller molecular weights of HA showed more rapid systemic distribution, while 67 and 215 kDa HA showed longer persistence in the lungs. Lung exposure appeared to be optimum in this size range due to the rapid absorption of <67 kDa HA and the poor lung penetration and mucociliary clearance of viscous solutions of HA > 215 kDa. The versatility of HA molecular weight and conjugation chemistries may, therefore, provide new opportunities to extend pulmonary drug exposure and potentially facilitate access to lymph nodes draining the pulmonary bed.

Patterns of Drug Use, Risky Behavior, and Health Status Among Persons Who Inject Drugs Living in San Diego, California: A Latent Class Analysis

Background: Among persons who inject drugs (PWID), polydrug use (the practice of mixing multiple drugs/alcohol sequentially or simultaneously) increases risk for HIV transmission and unintentional overdose deaths. Research has shown local drug markets influence drug use practices. However, little is known about the impact of drug mixing in markets dominated by black tar heroin and methamphetamine, such as the western United States. Methods: Data were collected through an ongoing longitudinal study examining drug use, risk behavior, and health status among PWID. Latent class analysis (LCA) was used to identify patterns of substance use (heroin, methamphetamine, prescription drugs, alcohol, and marijuana) via multiple administration routes (injecting, smoking, and swallowing). Logistic regression was used to identify behaviors and health indicators associated with drug use class. Results: The sample included 511 mostly white (51.5%) males (73.8%), with mean age of 43.5 years. Two distinct classes of drug users predominated: methamphetamine by multiple routes (51%) and heroin by injection (49%). In multivariable logistic regression, class membership was associated with age, race, and housing status. PWID who were HIV-seropositive and reported prior sexually transmitted infections had increased odds of belonging to the methamphetamine class. Those who were HCV positive and reported previous opioid overdose had an increased odds of being in the primarily heroin injection class (all P-values < .05). Conclusion: Risk behaviors and health outcomes differed between PWID who primarily inject heroin vs. those who use methamphetamine. The findings suggest that in a region where PWID mainly use black tar heroin or methamphetamine, interventions tailored to sub-populations of PWID could improve effectiveness.

SiRNA-based therapies for pulmonary diseases.

Various delivery strategies, involving siRNA as a therapeutic tool for gene silencing, have been highlighted through several investigations all over the world. One such medical target, where the siRNA-based therapies have been immensely explored and have met with considerable success, is the area of pulmonary disorders. Lung diseases have presented themselves as attractive targets for studying siRNA-mediated cures due to their widespread persistence and lethality. Another interesting feature in this case is that the lung is accessible to therapeutic agents via multiple administration routes including the nasal, oral and intravenous routes. Recent advances in pulmonary delivery highlight the exploitation of all these routes for administration of siRNA-based therapies, particularly by employing non-viral carriers like nanoparticles. Through this manuscript we aim to provide a comprehensive overview of the most important and the latest developments in non-viral siRNA delivery for lung diseases. We have focused our discussion on the diverse systems, which have been investigated for a plethora of pulmonary disorders, ranging from inflammatory conditions like asthma and COPD, to infectious diseases like tuberculosis, and to lung cancer. An overview of the preclinical and clinical investigations conducted in this area has also been presented to the readers. While a variety of these systems have been found to be promising in pre-clinical studies, their successful transition as therapeutics will ultimately depend upon their clinical safety and efficacy, as well as the specificity of the carriers and methods employed for their administration.