Pulmonary Route Research Articles

In vivo pharmacokinetic and pharmacodynamic study of co-spray-dried inhalable pirfenidone microparticles in rats

Pirfenidone (PRF) is the first FDA-approved API in the treatment of idiopathic pulmonary fibrosis (IPF). However, PRF induces serious side effects, such as photophobia and gastrointestinal disorder. PRF inhalation can be expected with a lower effective dose and reduced side effects. In this study, PRF was prepared as inhalable co-spray-dried particles for dry powder inhalation. Mannitol, L-leucine (Leu), and NaCl were used as a stabilizer. The kinds and ratios of stabilizers affecting the physicochemical properties of particles were analyzed, including particle size and surface composition, because of the surface enrichment properties of Leu, the most effective stabilizer. The co-spray-dried PRF and Leu microparticle (SD-PL1:1) have the smallest size and highest aerosol performance. The bioavailability was confirmed by in vivo pharmacokinetics (PK) studies. In addition, in vivo pharmacodynamics (PD) experiments were conducted using a bleomycin-induced IPF rat model. In vivo PK experiments demonstrated that pulmonary administration of SD-PL1:1 was 4 times more effective than the oral route. Similar to the PK results, the therapeutic effect was improved when SD-PL1:1 was administered via the pulmonary route compared to the oral route.

A Comprehensive Review on Targeted Drug Delivery System

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, and cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time.

Pulmonary Delivery of Favipiravir in Rats Reaches High Local Concentrations without Causing Oxidative Lung Injury or Systemic Side Effects.

Favipiravir displays a rapid viral clearance, a high recovery rate and broad therapeutic safety; however, its oral administration was associated with systemic side effects in susceptible patients. Considering that the pulmonary route could provide a high drug concentration, and a safer application with less absorption into systemic circulation, it was aimed to elucidate whether favipiravir delivered via soft-mist inhaler has any deleterious effects on lung, liver and kidney tissues of healthy rats. Wistar albino rats of both sexes (n = 72) were placed in restrainers, and were given either saline or favipiravir (1, 2.5, 5 or 10 mg/kg in 1 mL saline) by inhalation within 2 min for 5 consecutive days. On the 6th day, electrocardiographic recording was obtained, and cardiac blood and lung tissues were collected. Favipiravir did not alter cardiac rhythm, blood cell counts, serum levels of alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine, urea or uric acid, and did not cause any significant changes in the pulmonary malondialdehyde, myeloperoxidase activity or antioxidant glutathione levels. Our data revealed that pulmonary use of favipiravir via soft-mist inhaler enables a high local concentration compared to plasma without oxidative lung injury or cardiac or hepatorenal dysfunction.

Pharmacokinetics of Cannabidiol in Sprague-Dawley Rats After Oral and Pulmonary Administration.

Introduction: Cannabidiol (CBD) is primarily consumed through ingestion and inhalation. Little is known about how CBD pharmacokinetics differ between routes of administration, and duration of pulmonary exposure. Methods: Pharmacokinetics, brain distribution, and urinary elimination of CBD and its major metabolites (6-hydroxy-cannabidiol [6-OH-CBD], 7-hydroxy-cannabidiol [7-OH-CBD], 7-carboxy-cannabidiol [7-COOH-CBD], and CBD-glucuronide) were evaluated in adult Sprague-Dawley rats following a single oral CBD ingestion (10 mg/kg in medium chain triglyceride oil; 24 male animals), and 1 or 14 days of repeated inhalation (0.9-13.9 mg/kg in propylene glycol [41%/59% by weight]; 5 male and 5 female animals per dose). Blood and brain tissue were collected at a single time point from each animal. Collection times were staggered from 5 min to 24 h postoral gavage or first (blood only) and final inhalation. Urine was collected 24 h postoral gavage or final inhalation. Samples were analyzed through liquid chromatography-mass spectrometry (LC-MS/MS). Results: CBD was more rapidly absorbed following inhalation than ingestion (Tmax=5 min and 2 h, respectively). Inhalation resulted in a dose-responsive increase in CBD Cmax and AUClast. CBD Cmax was 24-fold higher following the highest pulmonary dose (13.9 mg/kg) versus an oral dose of comparable concentration (10 mg/kg). Cmax and AUClast (0-16 h) trended higher following repeated exposure. Elimination was notably faster with repeated CBD inhalation (t1/2=5.3 and 2.4 h on days 1 and 14, respectively). While metabolites were detectable in plasma, AUClast (0-2 h) was at least 10- (7-OH-CBD, 7-COOH-CBD) to 100- (6-OH-CBD) fold lower than the parent compound. Metabolite concentration trended higher following repeated inhalation (6.7 mg/kg CBD); AUClast (0-16 h) was ∼1.8-, ∼1.4-, and ∼2.4-fold higher following 14 days of exposure for 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, respectively. CBD was detectable in brain homogenate tissue 24-h after 14-day inhalation (>3.5 mg/kg deposited dose) or a single oral administration. CBD metabolites were only measurable in brain tissue following the highest inhaled dose (13.9 mg/kg CBD). CBD, but not metabolites, was detectable in urine for all dose groups following 2 weeks of CBD inhalation. Neither CBD nor metabolites were present in urine after oral administration. Conclusion: CBD pharmacokinetics differ across oral and pulmonary routes of administration and acute or repeated dosing.

“Novel mucoadhesive PLGA-PVM/MA micro-nanocomposites loaded with felodipine intended for pulmonary administration by nebulization”

Poly(latic-co-glycolic) acid (PLGA) nanoparticles loaded with felodipine (FEL) were embedded in a mucoadhesive matrix of poly (methyl vinyl ether-co-maleic anhydride) (PVM/MA) to prepare micro-nanoparticulate composites by particle engineering. Composites were characterized for physical and rheological properties and formulated with inhalable grade lactose. In-vitro characterization studies such as drug release kinetics, and mucoadhesive, and aerodynamic properties were performed. The in-vivo efficacy was evaluated by administering the optimized composites by nebulization in hypertensive rats. The obtained FEL-PLGA-PVM/MA composites of 1,069 ± 82 nm showed sustained drug release and mucoadhesive properties. Bulk and tapped densities of composites mixed with lactose were 0.08–0.13 g/mL and 0.18–0.30 g/mL, respectively, with mass median aerodynamic diameters (MMAD) in a range of 1.29–12.0 µm. After pulmonary administration of the composites, a decrease in systolic and diastolic blood pressure was observed within the first 3 h, of −9.0 ± 1.3 % and −13.9 ± 3.3 %, respectively, with a maximal effect at 12 h (sustained during 144 h), in contrast to pure FEL, which showed no significant decrease in blood pressure (1.6 ± 2.7 % and 4.1 ± 4.1 %). Findings suggest that novel mucoadhesive FEL-PLGA-PVM/MA composites are a promising strategy formulation to treat systemic diseases by pulmonary route.

A Promising Oral Drug Delivery System of Microsponges: A Brief Review

In the modern era of drug delivery, microsponges have their own tremendous properties of porous nature, due to this porous nature they have a capacity to entrap active drug and acts as a drug carrier because of this entrapment controlling the drug release and targeting the drug to a particular site is possible. Initially, this microsponge drug delivery has been used for topical route and later on oral route, recently, researches focused on the pulmonary and parenteral route of delivery. The present review aims at the development of microsponge technology in oral drug delivery, preparation, formulation considerations, characterization, recent advancements, and future prospects of microsponge drug delivery.

A review of formulations and preclinical studies of inhaled rifampicin for its clinical translation

Inhaled drug delivery is a promising approach to achieving high lung drug concentrations to facilitate efficient treatment of tuberculosis (TB) and to reduce the overall duration of treatment. Rifampicin is a good candidate for delivery via the pulmonary route. There have been no clinical studies yet at relevant inhaled doses despite the numerous studies investigating its formulation and preclinical properties for pulmonary delivery. This review discusses the clinical implications of pulmonary drug delivery in TB treatment, the drug delivery systems reported for pulmonary delivery of rifampicin, animal models, and the animal studies on inhaled rifampicin formulations, and the research gaps hindering the transition from preclinical development to clinical investigation. A review of reports in the literature suggested there have been minimal attempts to test inhaled formulations of rifampicin in laboratory animals at relevant high doses and there is a lack of appropriate studies in animal models. Published studies have reported testing only low doses (≤ 20 mg/kg) of rifampicin, and none of the studies has investigated the safety of inhaled rifampicin after repeated administration. Preclinical evaluations of inhaled anti-TB drugs, such as rifampicin, should include high-dose formulations in preclinical models, determined based on allometric conversions, for relevant high-dose anti-TB therapy in humans.Graphical abstract

Designing a ‘Ready-to-Use’ powder formulation platform for the inhaled protein therapeutics

New biologics development coupled with an emerging biosimilars manufacturing scene are poised to stimulate growth in the biotechnology industry. Parenteral delivery, currently the mainstay of therapy, is often associated with pain, infection risks, high costs and poor patient compliance. Hence, non-invasive routes are preferred. The oral route is limited by low bioavailability, while the pulmonary route has been advocated as an attractive non-invasive yet efficacious alternative that could be applied for both local and systemic therapies. The dry powder inhaler (DPI), being a stable, convenient and non-invasive delivery device, is increasingly being considered for biologics delivery. However, balancing the concurrent demands for optimal aerosolization, bioactivity and stability is often difficult, requiring considerable expertise and development times. This work has therefore utilized the Taguchi experimental design to innovatively scrutinize several equipment and formulation parameters, and to propose and develop a ‘Ready-to-Use’ powder formulation platform which could be used to minimize development times and be applied as a useful starting template for biologics DPI development. Via the application of a model protein (lysozyme) and the following template conditions: Nano Spray Dryer, trehalose at 20% w/w, NaCl at 5% w/w and l-leucine at 15–20% w/w, fine particle fractions (FPFs) and bioactivities as high as 68.3 ± 2.3% and 95.2 ± 5.0%, respectively, were readily obtained. It was found that optimal FPF and bioactivity was less dependent on the spray dryer type, and more reliant on the type and concentration of protective and lubricating excipients. The powders obtained through this platform, exhibited strong aerosolization-promoting features in their particles (e.g. surface corrugation, hollow cavities), had particles with d50 of ∼2.30 ± 0.04 μm and were also stable to moisture-induced transformations. Potentially, this platform could be a useful precursor formulation suited to a variety of inhaled biomolecules, with just minor adaptations required for niche demands/applications.

In vitro and in vivo local tolerability of a synergistic anti-tuberculosis drug combination intended for pulmonary delivery.

A drug combination, vancomycin (VAN) plus tetrahydrolipstatin (THL), has demonstrated an effective synergistic action in vitro against Mycobacterium tuberculosis (Mtb). The poor oral bioavailability of VAN and THL and the predominant tropism of Mtb infection to the lungs make their pulmonary administration very attractive. To evaluate their local tolerability, bronchial cells, alveolar cells and monocytes were exposed to concentrations around and above their minimal inhibitory concentration (MIC). The VAN had no inhibitory activity on the tested human cell lines, even at a concentration 125 times higher than its MIC, whereas the THL, alone or in combination with VAN, presented a cytostatic action. Monolayer epithelium showed no significant irreversible damage at concentrations up to 100 times the combination MIC. BALB/cAnNRj mice exposed to concentration of 50 times the combination MIC delivered endotracheally 3 times a week for 3 weeks showed no clinical signs or significant weight loss. The increase of proinflammatory biomarkers (i.e., IL-1, IL-6, TNF-α and proportion of inflammatory cells) and cytotoxicity in bronchoalveolar lavage fluid (BALF) were non-significant. Lung histopathology did not show significant tissue damage. The VAN/THL combination at doses up to 50 times the combination MIC is found to be thus well tolerated by pulmonary route. This study is a promising result and encouraging further investigations of pulmonary administration of VAN/THL combination as dry powder for anti-tuberculosis treatment.

Treatment of Tuberculosis in Nano Era: Recent Avenues

Abstract: Tuberculosis (TB) is a life-threatening infectious disease caused by the bacteria Mycobacterium tuberculosis (MTB), which mostly affects the lungs. According to the World Health Organization (WHO) report 2020, there were over 10 million cases of tuberculosis worldwide, with around 1.4 million people dying, wherein India accounts for over 26% of the global burden. Prolonged treatment, high pill burden, low compliance, development of multiple drug resistance and subsequent intolerable toxicity lead to the emergence of new nanotechnology-based drug delivery approaches involving micro-metric and nano-metric carriers. Nanotechnology is superior to conventional therapies as it offers site specific drug delivery of antimicrobial drugs that increases therapeutic efficacy and reduces systemic toxicity associated with higher doses and also prevents the drug from early degradation, increased solubility and blood retention time. This review focuses on the different nanotechnological carriers via pulmonary route, including liposomes, niosomes, solid lipid nanocarriers, dendrimers, nanoparticles, microspheres and microparticles for tackling the problems related to the treatment of TB. The current review gives a summary of the possible utilization of nanotechnology-based carrier systems to overcome the disadvantages of TB therapy. It also provides a summary of the importance and advancements of directing nanocarriers at bacterial reservoir. Eventually, the article presents an overview of the success in clinical application of such systems.

Molecular Insight into the Therapeutic Effects of Stem Cell-Derived Exosomes in Respiratory Diseases and the Potential for Pulmonary Delivery

Respiratory diseases are the cause of millions of deaths annually around the world. Despite the recent growth of our understanding of underlying mechanisms contributing to the pathogenesis of lung diseases, most therapeutic approaches are still limited to symptomatic treatments and therapies that only delay disease progression. Several clinical and preclinical studies have suggested stem cell (SC) therapy as a promising approach for treating various lung diseases. However, challenges such as the potential tumorigenicity, the low survival rate of the SCs in the recipient body, and difficulties in cell culturing and storage have limited the applicability of SC therapy. SC-derived extracellular vesicles (SC-EVs), particularly SC-derived exosomes (SC-Exos), exhibit most therapeutic properties of stem cells without their potential drawbacks. Similar to SCs, SC-Exos exhibit immunomodulatory, anti-inflammatory, and antifibrotic properties with the potential to be employed in the treatment of various inflammatory and chronic respiratory diseases. Furthermore, recent studies have demonstrated that the microRNA (miRNA) content of SC-Exos may play a crucial role in the therapeutic potential of these exosomes. Several studies have investigated the administration of SC-Exos via the pulmonary route, and techniques for SCs and SC-Exos delivery to the lungs by intratracheal instillation or inhalation have been developed. Here, we review the literature discussing the therapeutic effects of SC-Exos against respiratory diseases and advances in the pulmonary route of delivery of these exosomes to the damaged tissues.

Isoniazid Nano-drug Delivery Systems Targeting Macrophages for the Treatment of Tuberculosis

In the current clinical setting, the management of Mycobacterium tuberculosis remains a challenge. Isoniazid (INH) remains a drug of choice for treating tuberculosis (TB) via the conventional oral route. However, INH has low plasma levels due to its poor permeability into the bacterial cell. Furthermore, it has a short half-life of 1–4 h, indicating a brief residence in the plasma. Therefore, multiple administration frequencies at high doses are required, leading to multi-drug resistance and other side effects like nephrotoxicity. Lungs being the main target organ for TB, a pulmonary route of administration could be an alternative route to overcome such shortcomings. Due to multiple clearance mechanisms and biological barriers that restrict the entry of particles into the respiratory system, the pulmonary route of drug administration may not always be efficient. Thus, the era of nanotechnology has emerged as one of the most promising approaches to developing various drugs for overcoming such challenges. This review article highlights the anatomy and physiology of the lungs, the barriers to the pulmonary drug delivery system, and how these barriers decide the drug disposition at the target site. In addition, the various properties of the drug delivery systems such as size, shape, and charge have been discussed in the subsections, followed by various formulation-based drug delivery systems for INH, including preclinical investigation studies.

Expanding The Arsenal Against Pulmonary Diseases Using Surface-Functionalized Polymeric Micelles: Breakthroughs and Bottlenecks

Pulmonary diseases such as lung cancer, asthma and tuberculosis have remained one of the common challenges globally. Polymeric micelles (PMs) have emerged as an effective technique for achieving targeted drug delivery for a local as well as a systemic effect. These PMs encapsulate and protect hydrophobic drugs, increase pulmonary targeting, decrease side effects and enhance drug efficacy through the inhalation route. In the current review, emphasis has been placed on the different barriers encountered by the drugs given via the pulmonary route and the mechanism of PMs in achieving drug targeting. The applications of PMs in different pulmonary diseases have also been discussed in detail.

A Comprehensive Review of a New Nanosuspension for Improving the Oral Bioavailability of Poorly Soluble Drugs

Nanosuspension is a novel drug formulation for the delivery of hydrophobic drugs. The problem of medications that are poorly water-soluble and have low bioavailability is countered by nanosuspension technology. Solubility is a significant physiochemical element that influences drug absorption and therapeutic effectiveness. Poor aqueous solubility has the potential to impair formulation development. Nanosuspension technology can improve the drug's stability and bioavailability. Nanosuspensions can be formulated for various routes of administration such as oral, parenteral, ocular, topical, and pulmonary routes. Nanosuspension can be used for targeted drug delivery also by mucoadhesive gels and ocular inserts. Recent studies were approached to develop nanosuspension on site-specific drug delivery.

Calculating the Charcoal Blockade Efficiency for Bioequivalence Study of Inhaled Ipratropium Bromide Using A Model Method

Charcoal blockade is a useful approach to block gastrointestinal (GI) absorption of orally inhaled drug products (OIDPs) and therefore can be used effectively to determine drug absorption exclusively via the pulmonary route. Charcoal blockade efficiency (CBE) should be measured to show whether adequate blockade of GI exposure is achieved in bioequivalence (BE) study. The purpose of this study is to employ a model method to calculate the CBE for a pilot pharmacokinetic (PK) BE study of inhaled ipratropium bromide. This model method, based on a convolution integral, is built in-house using MATLAB package. The results demonstrated a full blockade of GI absorption of ipratropium bromide for both test and reference drug products. This study has shown that the model method may provide a useful approach for validation of charcoal blockade method used in PK BE study for OIDPs. The ability to use modeling may simplify human PK studies in general, and is particularly valuable when for ethical, technical or regulatory reasons administration of an orally swallowed form of the drug is not possible.

The effects of different doses of inhaled bacteriophage therapy for Pseudomonas aeruginosa pulmonary infections in mice

ObjectivesInhaled phage therapy has been revisited as a potential treatment option for respiratory infections caused by multidrug-resistant Pseudomonas aeruginosa; however, there is a distinct gap in understanding the dose–response effect. The aim of this study was to investigate the dose–response effect of Pseudomonas-targeting phage PEV31 delivered by the pulmonary route in a mouse lung infection model. MethodsNeutropenic BALB/c mice were infected with multidrug-resistant P. aeruginosa (2 × 104 colony-forming units) through the intratracheal route and then treated with PEV31 at three different doses of 7.5 × 104 (Group A), 5 × 106 (Group B), and 5 × 108 (Group C) plaque-forming units, or phosphate-buffered saline at 2 hours postinoculation. Mice (n = 5–7) were euthanized at 2 hours and 24 hours postinfection, and lungs, kidneys, spleen, liver, bronchoalveolar lavage fluid, and blood were collected for bacteria and phage enumeration. ResultsAt 24 hours postinfection, all phage-treated groups exhibited a significant reduction in pulmonary bacterial load by 1.3–1.9 log10, independent of the delivered phage dose. The extent of phage replication was negatively correlated with the dose administered, with log10 titre increases of 6.2, 2.7, and 9 for Groups A, B, and C, respectively. Phage-resistant bacterial subpopulations in the lung homogenate samples harvested at 24 hours postinfection increased with the treatment dose (i.e. 30%, 74%, and 91% in respective Groups A–C). However, the mutants showed increased susceptibility to ciprofloxacin, impaired twitching motility, and reduced blue-green pigment production. The expression of the inflammatory cytokines (IL-1ß and IL-6, and TNF-α) was suppressed with increasing PEV31 treatment dose. DiscussionThis study provides the dose–response effect of inhaled phage therapy that may guide dose selection for treating P. aeruginosa respiratory infections in humans.

Noninvasive Drug Delivery System Progress in Protein and Peptide Delivery

Protein and peptide drugs have tremendous therapeutic potential, and their usage in the treatment of various severe diseases has revolutionized the fields of pharmaceuticals and biotechnology. For successful therapeutic effects, several efforts have been made to deliver protein/peptide drugs through various routes of administration. Parenteral and nonparenteral drug deliveries are regarded as significant routes of drug absorption. However, there is a need to improve nonparenteral drug delivery systems (DDSs) through subsequent routes, including buccal, pulmonary, oral, ocular, transdermal, and nasal routes to increase drug absorption effectively. The study evaluated various DDS routes proposed for the distribution of proteins and peptides in terms of both parenteral and nonparenteral delivery systems. For this purpose, numerous research articles were searched from the year 2000 to 2021 using search engines such as PubMed, Google Scholar, Medline, ISI Web of Knowledge, and Bioline International while applying different keywords such as “protein and peptide drugs,” “drug delivery systems,” “parenteral and nonparenteral routes of drug delivery,” and “physicochemical barriers.” The invasive/parenteral routes have several limitations associated with drug delivery, such as poor patient compliance and the pain and discomfort associated with these routes inconvenience in treating the pediatric population. The oral route is one of the most convenient routes of noninvasive or nonparenteral drug administration; here, no pain and discomfort arise, thus helping in maintaining higher patient compliance or acceptance. The other routes of administration of proteins and peptides through buccal, intranasal, pulmonary, transdermal, rectal, and ocular routes have also been showing successful results. The success of the therapeutics is strongly influenced by the differential delivery of the targeted antigen, the choice of targeting protein or peptide, and the drug-release characteristics of the linker used. Furthermore, there should be an improvement in nonparenteral DDSs so that the drugs might be administered appropriately.

PH-responsive oleic acid based nanocarriers: Melanoma treatment strategies

Numerous clinical observations indicate that, despite novel therapeutic approaches, a high percentage of melanoma patients is non-responder or suffers of severe drug-related toxicity. To overcome these problems, we considered the option of designing, preparing and characterizing nanoemulsions and niosomes containing oleic acid, a pH-sensitive monounsaturated fatty acid holding per se an antimetastatic and anti-inflammatory role in melanoma. These new nanostructures will allow in vivo administration of oleic acid, otherwise toxic in its free form. For pulmonary route chitosan, a mucoadhesive agent, was enclosed in these nanocarriers to improve residence time at the lung site. A deep physical and chemical characterization was carried out evaluating size, ζ -potential, microviscosity, polarity as well as stability over time and in culture media. Moreover, their pH-sensitivity was evaluated by fluorometric assay. Cytotoxicity and cellular uptake were assessed in cultured normal fibroblasts and human melanoma cell lines. Interestingly, results obtained confirm nanocarrier stability and pH-sensitivity, associated to absence of cell toxicity, efficient cellular uptake and retention. Therefore, these new pH-sensitive oleic acid-based nanostructures could represent, by combining drug delivery in a pH-dependent manner with the antimetastatic potential of this fatty acid, a powerful strategy for more specific medicine against metastatic melanoma.

A Review on Lyotropic Liquid Crystals and Its Potential Applications

Backgraound: Novel drug delivery systems have always been of immense interest for research. Majority of the drugs suffers from solubity related constraints. Lipid based drug delivery systems provide a promising approach to address this issue.Amogst various approaches, liquid crystalline systems offers distinct advantages over other available options. It maintains the phase stablility between solid and liquid phases. Objective: Lyotropic Liquid Crystals (LLCs) have highly ordered internal structure forming capabilities thereby assisting the controlled release of a therapeutic agent of varying sizes and polarities. Methods: The present article covers the structural features of dispersed mesophases (cubosomes and hexosomes), components used to prepare various mesophases, method of preparation, characterization techniques and potential applications. Results: LLCsoffers a distinct choice for delivering hydrophobic as well as hydrophilic drug. They are also suitable for the delivery of macromolecules such as peptide and protiens through various routes of administration.Lyotropic liquid crystals are extremely versatile drug delivery systems that can be used for delivering drugs across topical, oral, buccal, pulmonary and intravenous routes. Their use in the delivery of tough to deliver drugs, hormones, peptides, biomolecules and vaccines is particularly important. Conclusion: This review discussed the composition, methods of preparation and characterization of LLCs. The LLCs offer promsing delivery choice for the drugs with lower solubility and higher toxicity.

Nebulizer systems: a new frontier for therapeutics and targeted delivery.

Drug delivery via the pulmonary route is a cornerstone in the pharmaceutical sector as an alternative to oral and parenteral administration. Nebulizer inhalation treatment offers multiple drug administration, easily employed with tidal breathing, suitable for children and elderly, can be adapted for severe patients and visible spray ensures patient satisfaction. This review discusses the operational and mechanical characteristics of nebulizer delivery devices in terms of aerosol production processes, their usage, benefits and drawbacks that are currently shaping the contemporary landscape of inhaled drug delivery. With the advent of particle engineering, novel inhaled nanosystems can be successfully developed to increase lung deposition and decrease pulmonary clearance. The above-mentioned advances might pave the path for treating a life-threatening disorder like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is also discussed in the current state of the art.