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Fulltext Concepts of advanced therapeutic delivery systems for the management of remodeling and inflammation in airway diseases

Dhanjal DS, Sharma P, Mehta M, Tambuwala MM, Prasher P, Paudel KR, et al.

Future Med Chem, 2022 Feb;14(4):271-288.
PMID: 35019757 DOI: 10.4155/fmc-2021-0081

Chronic respiratory disorders affect millions of people worldwide. Pathophysiological changes to the normal airway wall structure, including changes in the composition and organization of its cellular and molecular constituents, are referred to as airway remodeling. The inadequacy of effective treatment strategies and scarcity of novel therapies available for the treatment and management of chronic respiratory diseases have given rise to a serious impediment in the clinical management of such diseases. The progress made in advanced drug delivery, has offered additional advantages to fight against the emerging complications of airway remodeling. This review aims to address the gaps in current knowledge about airway remodeling, the relationships between remodeling, inflammation, clinical phenotypes and the significance of using novel drug delivery methods.
Recent update on anti-dengue drug discovery

Dighe SN, Ekwudu O, Dua K, Chellappan DK, Katavic PL, Collet TA

Eur J Med Chem, 2019 Aug 15;176:431-455.
PMID: 31128447 DOI: 10.1016/j.ejmech.2019.05.010

Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact on public health, there are no antiviral therapies available, and the only licensed vaccine, Dengvaxia®, has been contraindicated in children below nine years of age. In an effort to combat dengue, several small molecules have entered into human clinical trials. Here, we review anti-DENV molecules and their drug targets that have been published within the past five years (2014-2018). Further, we discuss their probable mechanisms of action and describe a role for classes of clinically approved drugs and also an unclassified class of anti-DENV agents. This review aims to enhance our understanding of novel agents and their cognate targets in furthering innovations in the use of small molecules for dengue drug therapies.
Genus Blepharis (Acanthaceae): A review of ethnomedicinally used species, and their phytochemistry and pharmacological activities

Dirar AI, Adhikari-Devkota A, Kunwar RM, Paudel KR, Belwal T, Gupta G, et al.

J Ethnopharmacol, 2021 Jan 30;265:113255.
PMID: 32798615 DOI: 10.1016/j.jep.2020.113255

ETHNOPHARMACOLOGICAL RELEVANCE: Blepharis is an Afro-Asiatic genus belonging to the family Acanthaceae. It comprises about 126 species that occur in arid and semi-arid habitats. Some species of Blepharis are used in traditional medicines in different countries mainly for their anti-inflammatory, wound healing activities along with treatment of gastrointestinal disorders and bone fractures.
AIM OF THE REVIEW: The present review aims to collate and analyze the available data and information on distribution, traditional uses, chemical constituents and pharmacological activities of Blepharis.
METHODS: Scientific information of genus Blepharis was retrieved from the online bibliographic databases such as MEDLINE/PubMed, SciFinder, Web of Science and Google Scholar and secondary resources including books and proceedings.
RESULTS: Seven species of Blepharis were found to be reported frequently as useful in folklore in African and Asian countries. B. maderaspatensis was found to be widely used in Indian traditional medicines whereas the B. ciliaris and B. edulis were common in folklore of Egypt, Jordan, and Arabia. Active phytochemicals of Blepharis are flavonoids from B. ciliaris, alkaloids from B. sindica, phenolic acid derivatives, and phytosterols, and derivatives of hydroxamic acids from B. edulis resulted in possessing diverse biological properties such as anti-microbial, anti-inflammatory, and anti-cancer.
CONCLUSIONS: Various species of Blepharis were found to be used in traditional medicine systems in African and Asian countries. Few of these species were studied for their bioactive chemical constituents however the activity guided isolation studies are not performed. Similarly, detailed pharmacological studies in animal models to explore their mechanism of action are also not reported. Future studies should focus on these aspects related to the medicinally used species of Blepharis. The detailed and comprehensive comparative analysis presented here gives valuable information of the currently used Blepharis species and pave the way to investigate other useful species of Blepharis pertaining to ethnobotany, phytochemistry and discovery of new drugs.
Fulltext Formulation, characterization, in vitro, in vivo, and histopathological evaluation of transdermal drug delivery containing norfloxacin and Curcuma longa

Dua K, Chakravarthi S, Kumar D, Sheshala R, Gupta G

Int J Pharm Investig, 2013 Oct;3(4):183-7.
PMID: 24350037 DOI: 10.4103/2230-973X.121287

In an attempt for better treatment of bacterial infections and burn wounds, semisolid formulations containing norfloxacin (NF) and natural wound healing agent Curcuma longa were prepared. The rationale behind employing combination of NF and Curcuma longa is to obtain synergistic wound healing effect. The prepared formulations were compared with silver sulfadiazine cream 1%, USP.
Fulltext Dissolution behavior of β-cyclodextrin molecular inclusion complexes of aceclofenac

Dua K, Pabreja K, Ramana MV, Lather V

J Pharm Bioallied Sci, 2011 Jul;3(3):417-25.
PMID: 21966164 DOI: 10.4103/0975-7406.84457

The objective of the present investigation was to study the effect of β-cyclodextrin (β-CD) on the in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. Aceclofenac molecular inclusion complexes in 1:1 and 1:2 M ratio were prepared using a kneading method. The in vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes was carried out. Molecular inclusion complexes of AF with β-CD showed a considerable increase in the dissolution rate in comparison with the physical mixture and pure drug in 0.1 N HCl, pH 1.2, and phosphate buffer, pH 7.4. Inclusion complexes with a 1:2 M ratio showed the maximum dissolution rate in comparison to other ratios. Fourier transform infrared spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and β-CD in complexes in solid state. Molecular modeling results indicated the relative energetic stability of the β-CD dimer-AF complex as compared to β-CD monomer-AF. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with β-CD. The in vitro release from all the formulations was best described by first-order kinetics (R(2) = 0.9826 and 0.9938 in 0.1 N HCl and phosphate buffer, respectively) followed by the Higuchi release model (R(2) = 0.9542 and 0.9686 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, the dissolution of AF can be enhanced by the use of a hydrophilic carrier like β-CD.
Aceclofenac topical dosage forms: in vitro and in vivo characterization

Dua K, Pabreja K, Ramana MV

Acta Pharm, 2010 Dec;60(4):467-78.
PMID: 21169138 DOI: 10.2478/v1007-010-0036-5

Aceclofenac is a new generation non-steroidal anti-inflammatory drug showing effective anti-inflammatory and analgesic properties. It is available in the form of tablets of 100 mg. Importance of aceclofenac as a NSAID has inspired development of topical dosage forms. This mode of administration may help avoid typical side effects associated with oral administration of NSAIDs, which have led to its withdrawal. Furthermore, aceclofenac topical dosage forms can be used as a supplement to oral therapy for better treatment of conditions such as arthritis. Ointments, creams, and gels containing 1% (m/m) aceclofenac have been prepared. They were tested for physical appearance, pH, spreadability, extrudability, drug content uniformity, in vitro diffusion and in vitro permeation. Gels prepared using Carbopol 940 (AF2, AF3) and macrogol bases (AF7) were selected after the analysis of the results. They were evaluated for acute skin irritancy, anti-inflammatory and analgesic effects using the carrageenan-induced thermal hyperalgesia and paw edema method. AF2 was shown to be significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to AF3 and AF7. Hence, AF2 may be suggested as an alternative to oral preparations.
Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review

Dua K, Sheshala R, Ling TY, Hui Ling S, Gorajana A

Antiinflamm Antiallergy Agents Med Chem, 2013;12(2):158-64.
PMID: 23286236

At present, approximately 25%of drugs in modern pharmacopoeia are derived from plant sources (phytomedicines) that can be developed for the treatment of diseases and disorders. Many other drugs are synthetic analogues built on the prototype compounds isolated from plants. Cocos nucifera Linn. (Arecaceae), which is commonly known as coconut, is a plant possessing a lot of potential as an ingredient in traditional medicines for the treatment of metabolic disorders and particularly as an anti-inflammatory, antimicrobial and analgesic agent. This review emphasizes on the recent literature and research findings that highlight the significant biological activities of C. nucifera Linn. such as its anti-inflammatory, antimicrobial and analgesic properties. This review can help researchers keen on exploiting the therapeutic potential of C. nucifera Linn. which may motivate them to further explore their commercial viability.
Antimicrobial Efficacy of Extemporaneously Prepared Herbal Mouthwashes

Dua K, Sheshala R, Al-Waeli HA, Gupta G, Chellappan DK

Recent Pat Drug Deliv Formul, 2015;9(3):257-61.
PMID: 26051152

Natural products like plants and its components have been in use for treatment and cure of diseases all around the globe from ancient times much before the discovery of the current modern drugs. These substances from the nature are well known to contain components which have therapeutic properties and can also behave as precursors for the synthesis of potential drugs. The beneficial results from herbal drugs are well reported where their popularity in usage has increased across the globe. Subsequently developing countries are now recognizing the many positive advantages from their use which has engaged the expansion of R & D from herbal research. The flow on effect from this expansion has increased the awareness to develop new herbal products and the processes, throughout the entire world. Mouth washes and mouth rinses which have plant oils, plant components or extracts have generated particular attention. High prevalence of gingival inflammation and periodontal diseases, suggests majority of the patients practice inadequate plaque control. Of the currently available mouthwashes in the market, Chlorhexidine gluconate (CHX) has been investigated on a larger scale with much detail. CHX is associated with side effects like staining of teeth when used daily as well as the bitter taste of the mouthwash which leads to patient incompliance. The present research encompasses the antibacterial activity of extemporaneously prepared herbal mouthwash using natural herbs and therefore allows for the potential commercialization with in the herbal and pharmaceutical industries. Also, the present research article reviewed details of various existing patents of herbal mouthwashes which shows the trend of existing market and significance of emerging mouthwashes in both pharmaceutical and herbal industries. The antimicrobial activity of prepared mouthwashes was found to be effective against various strains of bacteria. It also suggests that the prepared herbal mouthwashes may provide an alternative to those containing chemical entities, with enhanced antimicrobial properties and better patient compliance.
Nanoparticle-based therapies as a modality in treating wounds and preventing biofilm

Dua K, Gupta G, Chellapan DK, Bebawy M, Collet T

Panminerva Med, 2018 Dec;60(4):237-238.
PMID: 30563307 DOI: 10.23736/S0031-0808.18.03435-3
Targeting microRNAs using nanotechnology in pulmonary diseases

Dua K, Chellappan DK, Singhvi G, de Jesus Andreoli Pinto T, Gupta G, Hansbro PM

Panminerva Med, 2018 Dec;60(4):230-231.
PMID: 30563304 DOI: 10.23736/S0031-0808.18.03459-6
Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems

Dua K, Malyla V, Singhvi G, Wadhwa R, Krishna RV, Shukla SD, et al.

Chem Biol Interact, 2019 Feb 01;299:168-178.
PMID: 30553721 DOI: 10.1016/j.cbi.2018.12.009

Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic.
Multi-drug resistant Mycobacterium tuberculosis & oxidative stress complexity: Emerging need for novel drug delivery approaches

Dua K, Rapalli VK, Shukla SD, Singhvi G, Shastri MD, Chellappan DK, et al.

Biomed Pharmacother, 2018 Nov;107:1218-1229.
PMID: 30257336 DOI: 10.1016/j.biopha.2018.08.101

Tuberculosis (caused by Mycobacterium tuberculosis, Mtb) treatment involves multiple drug regimens for a prolonged period. However, the therapeutic benefit is often limited by poor patient compliance, subsequently leading to treatment failure and development of antibiotic resistance. Notably, oxidative stress is a crucial underlying factor that adversely influences the various treatment regimens in tuberculosis. Little information is available with advanced drug delivery systems that could be effectively utilized, in particular, for targeting the oxidative stress in tuberculosis. Thus, this presents an opportunity to review the utility of various available, controlled-release drug delivery systems (e.g., microspheres, liposomes, niosomes, solid lipid nanoparticles, dendrimers) that could be beneficial in tuberculosis treatments. This will help the biological and formulation scientists to pave a new path in formulating a treatment regimen for multi-drug resistant Mtb.
Fulltext Why is there an emerging need to look for a suitable drug delivery platform in targeting and regulating microbiota?

Dua K, Gupta G, Awasthi R, Chellappan DK

Panminerva Med, 2018 09;60(3):136-137.
PMID: 30176703 DOI: 10.23736/S0031-0808.18.03446-8
Fulltext Nanotechnology in drug delivery gaining new perspectives in respiratory diseases

Dua K, Madan JR, Chellappan DK, Gupta G

Panminerva Med, 2018 09;60(3):135-136.
PMID: 30176702 DOI: 10.23736/S0031-0808.18.03442-0
Targeting bacterial biofilms in pulmonary diseases in pediatric population

Dua K, Gupta G, Chellappan DK, Shukla S, Hansbro PM

Minerva Pediatr., 2018 Nov 07.
PMID: 30419743 DOI: 10.23736/S0026-4946.18.05256-8
The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress

Dua K, Wadhwa R, Singhvi G, Rapalli V, Shukla SD, Shastri MD, et al.

Drug Dev Res, 2019 09;80(6):714-730.
PMID: 31691339 DOI: 10.1002/ddr.21571

Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.
Chitosan and Its Derivatives in Nanocarrier Based Pulmonary Drug Delivery Systems

Dua K

Pharm Nanotechnol, 2017 Aug 07.
PMID: 28786352 DOI: 10.2174/2211738505666170808095258

BACKGROUND: Respiratory tract being a non-invasive route of drug administration is gaining massive attention in the present time to achieve both local and the systemic effects. In order to achieve effective therapeutic effects of a drug in the pulmonary region, it requires challenging barriers like mucociliary clearance and uptake by macrophages. An effective drug delivery system delivers the therapeutically active moieties at the right time, rate and in a reproducible manner to target sites for the effectively the human illnesses. A major limitation associated with most of the currently available conventional and controlled release drug delivery devices is that not all the drug candidates are well absorbed uniformly locally or systemically.
METHODS: We searched for the chitosan and its derivatives based nanocarrier systems for the pulmonary drug delivery. We focused on the applications of chitosan in the development of nanoparticles for the pulmonary drug delivery.
RESULTS: Chitosan, a natural linear bio poly amino saccharide is playing a crucial role in the development of novel drug delivery systems (NDDS) such as nanoparticles in order to treat various respiratory diseases effectively by managing these difficulties due to its unique characteristic properties of biodegradability, biocompatibility, mucoadhesivity and its ability to enhance macromolecule permeation. It also aids in providing sustained and targeted effects, which are the primary requirements of an ideal pulmonary drug delivery system. This review highlights the applications and importance of chitosan with special emphasis on nanotechnology, particularly employed in various respiratory diseases such as asthma, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis.
CONCLUSIONS: This review will be of interest to both the biological and formulation scientists to have a quick snapshot on the utility of chitosan in pulmonary drug delivery systems. At present, there are no patented chitosan based controlled release products available with pulmonary drug delivery and therefore this area needs attention to explore the potential of this polymer in the area of respiratory research.
Novel drug delivery approaches in treating pulmonary fibrosis

Dua K, Awasthi R, Madan JR, Chellappan DK, Nalluri BN, Gupta G, et al.

Panminerva Med, 2018 Dec;60(4):238-240.
PMID: 29480673 DOI: 10.23736/S0031-0808.18.03428-6
Fulltext Advancements in nano drug delivery systems: a challenge for biofilms in respiratory diseases

Dua K, de Jesus Andreoli Pinto T, Chellappan DK, Gupta G, Bebawy M, Hansbro PM

Panminerva Med, 2018 03;60(1):35-36.
PMID: 29370678 DOI: 10.23736/S0031-0808.18.03402-X
Fulltext Norfloxacin and metronidazole topical formulations for effective treatment of bacterial infections and burn wounds

Dua K, Malipeddi VR, Madan J, Gupta G, Chakravarthi S, Awasthi R, et al.

Interv Med Appl Sci, 2016 Jun 01;8(2):68-76.
PMID: 28386462 DOI: 10.1556/1646.8.2016.2.4

INTRODUCTION: Our various previous findings have shown the suitability of norfloxacin in the treatment of bacterial infections and burn wounds in alone as well as in combination with Curcuma longa in various topical (ointments, gels, and creams) and transdermal drug delivery systems.
AIMS AND METHODS: Keeping these facts in consideration, we have made an another attempt to prepare semisolid formulations containing 1% w/w of norfloxacin and metronidazole with different bases like Carbopol, polyethylene glycol, and hydroxypropylmethyl cellulose for effective treatment of bacterial infections and burn wounds. The prepared formulations were evaluated for physicochemical parameters, in vitro drug release, antimicrobial activity, and burn wound healing properties.
RESULTS: The prepared formulations were compared with Silver Sulfadiazine cream 1%, USP. Antimicrobial activity of norfloxacin semisolid formulations was found to be equally effective against both aerobic and anaerobic bacteria in comparison to a marketed formulation of Silver Sulfadiazine 1% cream, USP. Based on the burn wound healing property, the prepared norfloxacin semisolid formulation was found to be in good agreement with marketed Silver Sulfadiazine 1% cream, USP.
CONCLUSIONS: These findings suggest formulations containing norfloxacin and metronidazole may also prove as an effective alternative for existing remedies in the treatment of bacterial infections and burn wounds.

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