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Tofacitinib (TF) is a selective oral jakanib approved by the USFDA for the treatment of rheumatoid arthritis (RA). To overcome the adverse effects of orally administered TF, topical delivery can be a suitable choice. The therapeutic efficacy of TF can be improved through the high affinity of natural ligands (hyaluronic acid and chondroitin sulphate) to CD44 receptors on the macrophages or other immune cells in the dermal region. Thus, the present research work was inspired by the possibility to develop and evaluate the potential of hyaluronic acid-coated proglycosomes (HA-TF-PG) as the carrier for site-specific dermal delivery. The normal-PG (N-TF-PG) and HA-TF-PG showed particle sizes of250 nm. The HA-TF-PG demonstrated 3.15-fold higher retention of TF in the viable dermis layers than the conventional formulation. The in vivo pharmacodynamic study, cytokines, and radiographic study on Complete Freud's Adjuvant-induced arthritic rat model revealed that HA-TF-PG exhibited a significant (P 0.001) reduction in inflammation in arthritic rat's paw compared to the conventional TF. The developed HA-TF-PG treated groups showed significantly lowered CD44 levels compared to FD-gel and N-TF-PG i.e. 2.28 and 1.32-fold respectively (p 0.001). In conclusion, The HA-TF-PG can be developed as an effective carrier for the site-specific dermal drug delivery system of TF to treat RA.

For the past few years, there has been a surge in the use of nutraceuticals. The global nutraceuticals market in 2020 was USD 417.66 billion, and the market value is expected to increase by 8.9% compound annual growth rate from 2020 to 2028. This is because nutraceuticals are used to treat and prevent various diseases such as cancer, skin disorders, gastrointestinal, ophthalmic, diabetes, obesity, and central nervous system-related diseases. Nutritious food provides the required amount of nutrition to the human body through diet, whereas most of the bioactive agents present in the nutrients are highly lipophilic, with low aqueous solubility leading to poor dissolution and oral bioavailability. Also, the nutraceuticals like curcumin, carotenoids, anthocyanins, omega-3 fatty acids, vitamins C, vitamin B12, and quercetin have limitations such as poor solubility, chemical instability, bitter taste, and an unpleasant odor. Additionally, the presence of gastrointestinal (GIT) membrane barriers, varied pH, and reaction with GIT enzymes cause the degradation of some of the nutraceuticals. Nanotechnology-based nutrient delivery systems can be used to improve oral bioavailability by increasing nutraceutical stability in foods and GIT, increasing nutraceutical solubility in intestinal fluids, and decreasing first-pass metabolism in the gut and liver. This article has compiled the properties and applications of various nanocarriers such as polymeric nanoparticles, micelles, liposomes, niosomes, solid lipid nanocarriers, nanostructured lipid carrier, microemulsion, nanoemulsion, dendrimers in organic nanoparticles, and nanocomposites for effective delivery of bioactive molecules.

Background Tofacitinib—an oral JAK inhibitor—has been recently approved by US FDA to treat moderate to severe RA. The delivery of tofacitinib to specific inflammation site at joint via topical route using nanoformulations helps in managing the potential adverse effects. The objective is to develop and validate a simple, specific, and sensitive stability-indicating HPLC method for quantification of tofacitinib in topical nanoformulations and different matrices (adhesive tape, and skin layers, i.e., stratum corneum, viable epidermis, and dermis). The major objective was to avoid use of instruments like LC–MS/MS and to ensure a widespread application of the method. Result A 32 factorial ‘design of experiments’ was applied to optimize process variables, to understand the effect of variables on peak properties. The calibration curve showed regression coefficient (R2) 0.9999 and linearity in the concentration range of 50 to 15,000 ng/mL, which is suitable for the analysis of conventional dosage forms and nanoformulations. Method validation was performed as per ICH guideline Q2 (R1). The accuracy by recovery studies ranged between 98.09 and 100.82%. The % relative standard deviations in intraday and interday precisions were in the range of 1.16–1.72 and 1.22–1.80%, respectively. Forced degradation studies indicated the specificity of method and showed stability-indicating potential for tofacitinib peak. Conclusion The validated method provides a quantification method of tofacitinib in the presence of formulation excipients, dissolution media, and skin tissues in detail. In addition, the method was successfully utilized for determination of various dermatokinetics profile of tofacitinib.

Psoriasis is a multifactorial chronic autoimmune skin disorder, the exact cause of which is still under investigation. It is classified into different types displaying various histopathological features such as hyperproliferation, irregular parakeratosis and vascular infiltration of various immune cells with neutrophils in the epidermis. Over the past few decades, psoriasis pathogenesis has been thoroughly researched, leading to several advances in the treatment using small molecules and biologics. This review focuses on describing the role of various signaling pathways, including PDE-4, JAK-STAT, S1P, A

Ocular drug delivery is a significantly challenging task due to the presence of various anatomical and physiological barriers in the eye. Naturally available polysaccharides, when used as drug vehicles provide increased retention time, bioavailability, and penetration due to their unique mucoadhesive and charge-possessing nature. This review discusses the polysaccharide-based drug delivery system for the eye. Polysaccharides like alginic acid, cellulose derivatives, chitosan, pectin, xanthan gum, gellan gum, and hyaluronic acid are reviewed in this report. Additionally, emphasis is given to some of the recently investigated polymers such as sugarcane bagasse cellulose, a polysaccharide extracted from the seeds of Manilkara zapota, and Tremella fuciformis polysaccharide as drug vehicles for effective ocular drug delivery. This review also provides insight on clinical status and FDA-approved polysaccharides for ophthalmic delivery of therapeutics.

The current drug therapies for treating rheumatoid arthritis (RA) include nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, or biological products designed to mitigate the symptoms of the disease. These therapies with conventional delivery systems possess limitations such as lack of selectivity and adverse effects in the extra-articular tissues. Microneedles-based transdermal drug delivery gained huge attention that can overcome the limitations associated with conventional preparations.This review aims to provide detailed information on types of microneedles (MNs) and their usage in drug delivery for the management of RA. In addition, it also provides evidence for the effective use of MNs in RA treatment. Various types of MNs, their regulatory status, clinical trials, and patents are also compiled in this review.Microneedles are small patch-like structures consisting of needles in micron range arranged in array-like structure used to manage drugs designed to be given via transdermal route. Microneedles provide painless delivery, fast onset of action, bypass the first-pass metabolism, and be easily self-administered. In the case of RA treatment, which requires a long-term application of drugs, MN is a new and emerging way to ease the symptoms of RA.

The purpose of the present study was to optimise diclofenac diethylamine-loaded liquid crystal nanoparticles (LCNPs) using the principles of quality by design. Based on risk assessment, the effect ...

Background: Skin diseases affect all the age groups of people and have an impact on patients’ physical, mental, and emotional status. Conventional topical preparation is limited with its efficacy due to low permeation, frequent application, and poor adherence to the therapy for prolong time. Objective: The objective of this review article is to address the emerging trends of nanotechnology derived lipidic carrier systems for an effective treatment for skin disorders. Methodology: Various research and review articles from reputed international journals were referred and compiled. Results and Discussion: opical drug delivery systems were found to be more effective than oral and parenteral drug delivery systems for treating skin diseases due to targeted localized applications with reduced side effects. Lipid-based nanoparticles have been found to have the potential in treating skin diseases due to the biocompatibility and the versatility of the lipids. Nanostructured lipid carriers (NLCs) have gained much attention in treating skin diseases due to improved stability of the drugs, enhanced skin permeation, retention, and better therapeutic efficacy. The review summarizes the NLCs characteristics and their application for topical delivery of various therapeutics in skin disorders. NLCs have shown great potential in effective drug delivery for the treatment of psoriasis, dermatitis, bacterial infections, and skin cancer. Its cosmetic application has opened a new area for skincare. Furthermore, safety and clinical status revealed its future commercial acceptability. Conclusion: NLCs have been found as effective lipid nanocarriers for the delivery of topical therapeutics.

Hydrogels are aqueous gels composed of cross-linked networks of hydrophilic polymers. Stimuli-responsive based hydrogels have gained focus over the past 20 years for treating ophthalmic diseases. Different stimuli-responsive mechanisms are involved in forming polymer hydrogel networks, including change in temperature, pH, ions, and others including light, thrombin, pressure, antigen, and glucose-responsive. Incorporation of nanocarriers with these smart stimuli-responsive drug delivery systems that can extend the duration of action by increasing ocular bioavailability and reducing the dosing frequency. This review will focus on the hydrogel drug delivery systems highlighting the gelling mechanisms and emerging stimuli-responsive hydrogels from preformed gels, nanogels, and the role of advanced 3D printed hydrogels in vision-threatening diseases like age-related macular degeneration and retinitis pigmentosa. It also provides insight into the limitations of hydrogels along with the safety and biocompatibility of the hydrogel drug delivery systems.

Age-related Macular Degeneration (AMD) is one of the common diseases affecting the posterior part of the eye, of a large population above 45 years old. Anti-Vascular Endothelial Growth Factor- A (Anti-VEGF-A) agents have been considered and approved as therapeutic agents for the treatment of AMD. Due to the large molecular weight and poor permeability through various eye membranes, VEGF-A inhibitors are given through an intravitreal injection, even though the delivery of small therapeutic molecules by topical application to the posterior part of the eye exhibits challenges in the treatment. To overcome these limitations, nanocarrier based delivery systems have been utilized to a large extent for the delivery of therapeutics. Nanocarriers system offers prodigious benefits for the delivery of therapeutics to the posterior part of the eye in both invasive and non-invasive techniques. The nano size can improve the permeation of therapeutic agent across the biological membranes. They provide protection from enzymes present at the site, targeted delivery or binding with the disease site and extend the release of therapeutic agents with prolonged retention. This leads to improved therapeutic efficacy, patient compliance, and cost effectiveness of therapy with minimum dose associated side-effects. This review has summarized various nanocarriers explored for the treatment of AMD and challenges in translation.

Temozolomide is a drug approved for treating glioblastomas, which has 100% oral bioavailability but gets degraded at physiological pH thus having very short half-life and only 20-30% brain bioavailability. Due to its amphiphilic nature, reported nanoformulations exhibits poor drug loading. The objective of this work was to formulate lipid-based drug delivery systems to enhance the brain bioavailability by prolonging the drug release and circulation time of the drug to overcome the limitations of the existing therapies and possible reduction of side effects. The size of the nanocarriers obtained was less than 300 nm and the PDI obtained was less than 0.3. The designed formulation showed higher entrapment efficiency as compared to the other reported nanocarriers of temozolomide. The designed formulations showed prolonged drug release from 12 to 20 h compared to 6 h for the pure drug. About 95% of the pure drug was degraded at plasma pH at the end of 12 h, whereas only 68% and 77% was degraded when entrapped inside the lipid crystal nanoparticles and proliposomes respectively. Further, pharmacokinetic and animal studies can confirm the potential of these for improvement of brain bioavailability.

Ocular diseases have a significant effect on vision and quality of life. Drug delivery to ocular tissues is a challenge to formulation scientists. The major barriers to delivering drugs to the anterior and posterior segments include physiological barriers (nasolacrimal drainage, blinking), anatomical barriers (static and dynamic), efflux pumps and metabolic barriers. The static barriers comprise the different layers of the cornea, sclera, and blood-aqueous barriers whereas dynamic barriers involve conjunctival blood flow, lymphatic clearance and tear drainage. The tight junctions of the blood-retinal barrier (BRB) restrict systemically administered drugs from entering the retina. Nanocarriers have been found to be effective at overcoming the issues associated with conventional ophthalmic dosage forms. Various nanocarriers, including nanodispersion systems, nanomicelles, lipidic nanocarriers, polymeric nanoparticles, liposomes, niosomes, and dendrimers, have been investigated for improved permeation and effective targeted drug delivery to various ophthalmic sites. In this review, various nanomedicines and their application for ophthalmic delivery of therapeutics are discussed. Additionally, scale-up and clinical status are also addressed to understand the current scenario for ophthalmic drug delivery.

INTRODUCTION Investigating the transportation of a drug molecule through various layers of skin and determining the amount of drug retention in skin layers is of prime importance in transdermal and topical drug delivery. The information regarding drug permeation and retention in skin layers aids in optimizing a formulation and provides insight into the therapeutic efficacy of a formulation. AREAS COVERED This perspective covers various methods that have been explored to estimate drug/therapeutics in skin layers using in vitro, ex vivo, and in vivo conditions. In vitro methods such as diffusion techniques, ex vivo methods such as isolated perfused skin models and in vivo techniques including dermato-pharmacokinetics employing tape stripping, and microdialysis are discussed. Application of all techniques at various stages of formulation development where various local and systemic effects need to be considered. EXPERT OPINION The void in the existing methodologies necessitates improvement in the field of dermatologic research. Standardization of protocols, experimental setups, regulatory guidelines, and further research provides information to select an alternative for human skin to perform skin permeation experiments to increase the reliability of data generated through the available techniques. There is a need to utilize multiple techniques for appropriate dermato-pharmacokinetics evaluation and formulation's efficacy.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the most recent coronaviruses, which has infected humans, and caused the disease COVID-19. The World Health Organization has declared COVID-19 as a pandemic in March 2020. The SARS-CoV-2 enters human hosts majorly via the respiratory tract, affecting the lungs first. In few critical cases, the infection progresses to failure of the respiratory system known as acute respiratory distress syndrome acute respiratory distress syndrome may be further associated with multi-organ failure and vasoplegic shock. Currently, the treatment of COVID-19 involves use of antiviral and anti-cytokine drugs. However, both the drugs have low efficacy because they cannot inhibit the production of free radicals and cytokines at the same time. Recently, some researchers have reported the use of methylene blue (MB) in COVID-19 management. MB has been used since a long time as a therapeutic agent, and has been approved by the US FDA for the treatment of other diseases. The additional advantage of MB is its low cost. MB is a safe drug when used in the dose of

Rheumatoid arthritis (RA) is a chronic systemic inflammatory condition that mainly affects the lining of the synovial joints. It can progressively cause disability and even premature death. Moreove...

The present study is concerned with the QbD-based design and development of luliconazole-loaded nanostructured lipid carriers (NLCs) hydrogel for enhanced skin retention and permeation. The NLCs formulation was optimized employing a 3-factor, 3-level Box-Behnken design. The effect of formulation variable lipid content, surfactant concentration, and sonication time was studied on particle size and % EE. The optimized formulation exhibited particle size of 86.480 ± 0.799 nm; 0.213 ± 0.004 PDI, ≥ − 10 mV zeta potential and 85.770 ± 0.503% EE. The in vitro release studies revealed sustained release of NLCs up to 42 h. The designed formulation showed desirable occlusivity, spreadability (0.748 ± 0.160), extrudability (3.130 ± 1.570), and the assay was found to be 99.520 ± 0.890%. The dermatokinetics assessment revealed the Cmax Skin to be ~ 2-fold higher and AUC0–24 to be ~ 3-fold higher in the epidermis and dermis of NLCs loaded gel in contrast with the marketed cream. The Tmax of both the formulations was found to be 6 h in the epidermis and dermis. The obtained results suggested that luliconazole NLCs can serve as a promising formulation to enhance luliconazole’s antifungal activity and also in increasing patient compliance by reducing the frequency of application.

Microneedles (MNs) fabrication using chitosan has gained significant interest due to its ability of film-forming, biodegradability, and biocompatibility, making it suitable for topical and transdermal drug delivery. The presence of amine and hydroxyl functional groups on chitosan permits the modification with tunable properties and functionalities. In this regard, chitosan is the preferred material for fabrication of MNs because it does not produce an immune response in the body and can be tailored as per required strength and functionalities. Therefore, many researchers have attempted to use chitosan as a drug delivery vehicle for hydrophilic drugs, peptides, and hormones. In 2020, the FDA has issued "Regulatory Considerations for Microneedling Products". This official guidance is a sign for future opportunities in the development of MNs. The present review focuses on properties, and modifications of chitosan used in the fabrication of MNs. The therapeutic and diagnostic applications of different types of chitosan-based MNs have been discussed. Further, the regulatory aspects of MN-based devices, and patents related to chitosan-based MNs are discussed.

Curcumin is a unique molecule naturally obtained from rhizomes of Curcuma longa. Curcumin has been reported to act on diverse molecular targets like receptors, enzymes, and co-factors; regulate different cellular signaling pathways; and modulate gene expression. It suppresses expression of main inflammatory mediators like interleukins, tumor necrosis factor, and nuclear factor κB which are involved in the regulation of genes causing inflammation in most skin disorders. The topical delivery of curcumin seems to be more advantageous in providing a localized effect in skin diseases. However, its low aqueous solubility, poor skin permeation, and degradation hinder its application for commercial use despite its enormous potential. Lipid-based nanocarrier systems including liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lyotropic liquid crystal nanoparticles, lipospheres, and lipid nanocapsules have found potential as carriers to overcome the issues associated with conventional topical dosage forms. Nano-size, lipophilic nature, viscoelastic properties, and occlusive effect of lipid nanocarriers provide high drug loading, hydration of skin, stability, enhanced permeation through the stratum corneum, and slow release of curcumin in the targeted skin layers. This review particularly focuses on the application of lipid nanocarriers for the topical delivery of curcumin in the treatment of various skin diseases. Furthermore, preclinical studies and patents have also indicated the emerging commercialization potential of curcumin-loaded lipid nanocarriers for effective drug delivery in skin disorders. Graphical Abstract.

There has been a surge in the use of transdermal drug delivery systems (TDDS) for the past few years. The market of TDDS is expected to reach USD 7.1 billion by 2023, from USD 5.7 billion in 2018, at a CAGR of 4.5%. Microneedles (MNs) are a novel class of TDDS with advantages of reduced pain, low infection risk, ease of application, controlled release of therapeutic agents, and enhanced bioavailability. Biodegradable MNs fabricated from natural polymers have become the center of attention among formulation scientists because of their recognized biodegradability, biocompatibility, ease of fabrication, and sustainable character. In this review, we summarize the various polysaccharides and polypeptide based biomaterials that are used to fabricate biodegradable MNs. Particular emphasis is given to cellulose and its derivatives, starch, and complex carbohydrate polymers such as alginates, chitosan, chondroitin sulfate, xanthan gum, pullulan, and hyaluronic acid. Additionally, novel protein-based polymers such as zein, collagen, gelatin, fish scale and silk fibroin (polyamino acid) biopolymers application in transdermal drug delivery have also been discussed. The current review will provide a unique perspective to the readers on the developments of biodegradable MNs composed of carbohydrates and protein polymers with their clinical applications and patent status.

Fungal infections are an important cause of morbidity and pose a serious health concern especially in immunocompromised patients. Luliconazole (LUL) is a topical imidazole antifungal drug with a broad spectrum of activity. To overcome the limitations of conventional dosage forms, LUL loaded lyotropic liquid crystalline nanoparticles (LCNP) were formulated and characterized using a three-factor, five-level Central Composite Design of Response Surface Methodology. LUL loaded LCNP showed particle size of 181 ± 12.3 nm with an entrapment efficiency of 91.49 ± 1.61 %. The LUL-LCNP dispersion in-vitro drug release showed extended release up to 54 h. Ex-vivo skin permeation studies revealed transdermal flux value (J) of LUL-LCNP gel (7.582 μg/h/cm2) 2 folds higher compared to marketed cream (3.3706 μg/h/cm2). The retention of LUL in the stratum corneum was ∼1.5 folds higher and ∼2 folds higher in the epidermis and other deeper layers in comparison to the marketed cream. The total amount of drug penetrated (AUC0-∞) with LCNP formulation was 4.7 folds higher in epidermis and 6.5 folds higher in dermis than marketed cream. The study's findings vouch that LCNP can be a promising and effective carrier system for the delivery of antifungal drugs with enhanced skin permeation.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that is characterized by synovial inflammation, cellular infiltration in joints which leads to progressive joint destruction and bone erosion. RA is associated with many comorbidities including pulmonary disease, rheumatoid nodules and can have a pessimistic impact on quality of life. The current therapies of RA treatment comprise conventional, small molecule and biological antirheumatic drugs. Their utility as therapeutic agents is limited because of poor absorption, rapid metabolism and adverse effects (dose-escalation, systemic toxicity, lack of selectivity and safety). To overcome these limitations, the novel drug delivery systems are being investigated. This review has compiled currently approved therapies along with emerging advanced drug-delivery systems for RA treatment. Further, active targeting of therapeutic agents to inflamed joints via folate receptor, CD44, angiogenesis, integrins and other provided an improved therapeutic efficacy in the treatment of RA.

The incidences of fungal infections have greatly increased over the past few years, particularly in humid and industrialized areas. The severity of such infections ranges from being asymptomatic-mild to potentially life-threatening systemic infections. There are limited classes of drugs that are approved for the treatment of such infections like polyenes, azoles, and echinocandins. Some fungi have developed resistance to these drugs. Therefore, to counter drug resistance, intensive large scale studies on novel targeting strategies and formulations are being conducted, which have gained impetus lately. Conventional formulations have limitations such as higher doses, frequent dosing, and several side effects. Such limiting factors have paved the path for the emergence of nanotechnology and its applications. This further gave formulation scientists the possibility of encapsulating the existing potential drug moieties into nanocarriers, which when loaded into gels or creams provided prolonged release and improved permeation, thus giving on-target effect. This review thus discusses the newer targeting strategies and the role of nanocarriers that could be administered topically for the treatment of various fungal infections. Furthermore, this approach opens newer avenues for continued and sustained research in pharmaceuticals with much more effective outcomes.

Psoriasis is a chronic autoimmune skin disorder triggered by either genetic factors, environmental factors, life style, or a combination thereof. Clinical investigations have identified pathogenesis, such as T cell and cytokine-mediated, genetic disposition, antimicrobial peptides, lipocalin-2, galectin-3, vaspin, fractalkine, and human neutrophil peptides in the progression of psoriasis. In addition to traditional therapies, newer therapeutics, including phosphodiesterase type 4 (PDE4) inhibitors, Janus kinase (JAK) inhibitors, monoclonal antibodies (mAbs), gene therapy, anti-T cell therapy, and phytoconstituents have been explored. In this review, we highlight nanotechnology-related developments for psoriasis treatment, including patented delivery systems and therapeutics currently in clinical trials.

Nanostructured lipid carriers (NLC) have become a promising drug delivery system for topical delivery of drugs. Delivery of lipophilic drugs with improved stability and entrapment efficiency is one of the foremost benefits of NLC based formulations. The objective of the present study was to improve the permeation of poorly soluble curcumin into topical skin layers for the treatment of chronic inflammatory disorder psoriasis and microbial mediated acne vulgaris. Hot emulsification followed by probe sonication method was employed for the preparation of the curcumin loaded NLC. Further, in-vitro and ex-vivo characterization was performed for designed NLC. The designed NLC showed a mean particle size 96.2 ± 0.9 nm, entrapment efficiency of 70.5 ± 1.65% and zeta potential of -15.2 ± 0.566 mV. Curcumin-NLC showed extended in-vitro release upto 48 hours, whereas free curcumin showed 100% drug release within 4 hours. Ex-vivo skin permeation studies revealed 3.24 fold improved permeation and skin retention in the case of curcumin loaded NLC gel compared to free curcumin gel. The cell viability studies demonstrated the formulation components showed no toxicity towards keratinocyte cells. In keratinocyte cells, improved cell uptake was observed for curcumin-NLC compared to free curcumin dispersion. The results suggested that the NLC based formulation had potential to improve the efficacy of curcumin.

The respiratory system is highly prone to a number of chronic disorders, which is one of the common health problems all over the world. Administration of therapeutics by oral or parenteral routes leads to minimal bioavailability at the therapeutic site, unwanted adverse events, and required frequent dosing. To overcome the limitations with respect to conventional delivery systems, advanced drug delivery systems like inhalable formulations had attained high priority. Inhalation-based formulations exhibit major challenges with particle size and the elimination of foreign particles from the lungs. The particle size of inhalable formulation has a critical role that can retain within the respiratory part and overcome the disadvantages of alveolar uptake. Micron-size particles like microparticles, microspheres, and microemulsions are found to an attractive strategy for effective delivery of drugs to the targeted sites. These particles can be settled in the deeper part of the respiratory system and overcome the disadvantages of normal powder for inhalation. The micron-size particles are modified as dry powder inhalers with good flow properties. Various techniques have been implemented for microparticle preparation, and modification is implemented to overcome alveolar macrophage uptake and mucoadhesion. The microparticulate systems can overcome the disadvantage of nanoparticles as nanoparticles can be encapsulated in microparticles. This minimizes the engulfing of nanoparticle, aggregation of nanoparticle, and exhalation of nanoparticles. The current microparticle-, microsphere-, and microemulsion-based formulation approaches are discussed to achieve better therapeutic efficacy in the treatment of respiratory disorders.

This study aimed to design and characterize Tofacitinib (TF)-loaded lyotropic liquid crystalline nanoparticles (TF-LCNP) gel using quality by design-driven approach to enhance the skin delivery of TF. The present work investigated the impact of two different liquid lipids on different critical quality attributes of LCNP. The optimized lyotropic liquid crystals system was constructed with the glyceryl monooleate,myristol, Lutrol® and water system. The optimized TF - LCNP showed particle size of 74.82 ± 4.26 nm, polydispersity index of 0.124 ± 0.024, and entrapment efficiency of 68.29 ± 5.24 %. The TF-LCNP showed sustained release for 24 h and followed quasi-Fickian diffusion from non-swellable matrix diffusion with n value of 0.197. The ex vivo permeation studies exhibited that amount of TF permeated through LCNP gel and cream after 24 h were found to be 61.11 ± 1.5 µg/cm2 and 37.7 ± 3.5 µg/cm2, respectively. The penetration mechanism of TF-LCNP gel through skin layers followed the Korsmeyer- Peppas model (n-value of 1.687), indicated Case-II relaxational release of TF. The tape stripping studies showed that TF loaded LCNPs retained 3 fold and 2.81 fold greater TF in stratum corneum and viable skin layers than conventional cream. The coumarin – 6 loaded LCNP study using Fluorescence microscopy confirmed the penetration of TF-LCNP into the deeper layers of skin. The dermal pharmacokinetic studies revealed that the LCNP showed a steady equilibrium state in 5–8 h in epidermis and dermis layers. The total amount of TF permeated with developed LCNP formulation was 3.42 times and 2.19 times higher in epidermis and dermis compared to the TF-cream. The developed formulation exhibited good spreadability and rheology and has not shown any significant changes in stability and scale-up studies. In a nutshell, the developed TF-LCNP strategy poses excellent potential in targeting the viable skin layer.

Psoriasis is a common immune-mediated inflammatory skin disease. It includes multifaceted interaction between the immune system and the keratinocytes. Recent studies depicted the role of microRNAs (miRNAs) in hyperproliferation of keratinocytes and inflammatory cytokine production, which serve as biomarkers for diagnosis, monitoring treatment response, and prognosis. miRNAs are small nucleotide sequenced noncoding RNAs. Deregulation of miRNAs was found to be the most common factor in the studies pertaining to psoriasis. Hence, miRNA-based targeting for psoriasis treatment became the primary field of current research. miRNA due to its spatial and chemical properties offer different challenges in the process of its delivery. The topical delivery of different siRNAs and genes has paved a way to similar delivery of miRNA. The topical delivery of miRNAs to the skin can bring a revolutionary change in the field of psoriasis treatment.

Lipid nanocapsules (LNCs) are lipid-based nanocarriers that have found application as drug delivery systems, in diagnostics, and theranostics. They are biocompatible and able to circumvent biological membranes easily because of their morphological features and structural facets. This article aims to review lipid shell lipid nanocapsules as a smart generation of lipid nanocarriers. These nanocapsules are prepared by the method of phase inversion temperature because of low energy consumption and easy scale-up. Further, the composition, method of preparation, the effect of surface modification of LNCs, medical/biomedical applications, and patents have been described with the help of reported studies. In the end, an attempt has been made to understand the future prospects of employing LNCs as delivery systems. This review will provide a unique perspective to the readers, and help them in empathizing with the far-reaching implications of LNCs as smart generation of lipid nanocarriers.

The intersection of lipid-based nanoparticles and lyotropic liquid crystals has provided a novel type of nanocarrier system known as ‘lipid-based lyotropic liquid crystals’ or ‘liquid crystalline nanoparticles’ (LCNPs). The unique advantages and immense popularity of LCNPs can be exploited in a better way if the formulation of LCNPs is done using the approach of quality by design (QbD). QbD is a systematic method that can be utilized in formulation development. When QbD is applied to LCNPs formulation, it will proffer many unique advantages, such as better product and process understanding, the flexibility of process within the design space, implementation of more effective and efficient control strategies, easy transfer from bench to bedside, and more robust product. In this work, the application of QbD in the formulation of LCNPs has been explored. The elements of QbD, viz. quality target product profile, critical quality attributes, critical material attributes, critical process parameters, quality risk management, design of experiments, and control strategy for the development of LCNPs have been explained in-depth with case studies. The present work will help the reader to understand the nitty-gritties in the application of QbD in the formulation of LCNPs, and provide a base for QbD-driven formulation of LCNPs with a regulatory perspective.

Tofacitinib is an oral Janus kinase inhibitor used in the treatment of Rheumatoid arthritis. The topical delivery of novel Tofacitinib loaded liquid crystal nanoparticles (LCNPs) can provide a controlled release, and also targeted drug delivery to inflamed synovium. There is need of UV spectroscopic method which can determine Tofacitinib in designed nanocarriers like LCNPs, that can be applied to evaluate entrapment efficiency, in vitro drug release, and ex vivo skin studies. In the present study, we have developed and validated a simple and sensitive spectrophotometric method for the quantitative determination of Tofacitinib in methanol and phosphate buffer saline. The linearity range in both the media was 5–30 µg/mL (methanol) and 5–40 µg/ mL (phosphate buffer saline) with high correlation coefficient value (>0.9998). This indicates the clear correlation between Tofacitinib concentrations and their absorbance within the test ranges. The repeatability and intermediate precision articulated by the relative standard deviation were less than 2% in the developed method. The method specificity and applicability were also ascertained by performing recovery studies by spiking method, which was 95.85 ± 1.98% with % RSD 1.24 ± 0.045. The method developed in methanol was successfully applied to determine the entrapment efficiency of Tofacitinib in developed LCNPs formulation and skin retention (dermatokinetics). The method developed in pH 7.4 phosphate buffer saline was applied to quantify Tofacitinib from LCNPs in in vitro and ex vivo drug release samples. In conclusion, a simple, sensitive, accurate, and precise UV spectrophotometric method was established to determine Tofacitinib in in vitro and ex vivo skin studies.

Low-potency corticosteroid betamethasone valerate and vitamin-A tazarotene are used in combination for effective treatment of psoriasis. There is no robust high-performance liquid chromatography analytical technique available for simultaneous estimation of betamethasone valerate and tazarotene in conventional and nanocarriers based formulations. A simple, accurate, robust isocratic high-performance liquid chromatography method was developed for simultaneous estimation of betamethasone valerate and tazarotene in topical pharmaceutical formulations. The developed method was validated as per the regulatory guidelines. The validated method was linear over the concentration range of 150-6000 ng/mL (r2 > 0.999) at 239 nm wavelength. Limits of detection and quantification of two analytes were 50 and 150 ng/mL, respectively. The %relative standard deviation for intraday and interday precision was less than 2%. The method was also evaluated in the presence of forced degradation conditions. The developed method was successfully applied for in vitro and ex vivo drug release studies of in-house designed nanoformulations.

Curcumin the extract obtained from the dried rhizome of turmeric, Curcuma longa is a hydrophobic phenol that delivers numerous pharmacological actions like anti-inflammatory, anti-microbial and anti-oxidant, anti-psoriasis, antidiabetic, anticancer. But curcumin has low bioavailability issues that accompany low aqueous solubility, further, when administered orally, >90% of the drug degrades rapidly in the alkaline medium. Administering the drug topically can bypass the problem as well as first-pass metabolism and therefore delivering the drug at the targeted site of action. Encapsulating curcumin in nanostructured lipid nanocarriers (NLC) is an excellent novel strategy. Further, these NLC provides both the controlled release and helps in the enhanced permeation of the drug through the skin's physiological barrier, stratum corneum. For the NLC characterization, a reliable method must be developed that can accurately and precisely determine the drug content in the formulation and also for its in-vitro and ex-vivo characterization. This experiment describes the analytical validation parameters described as per International Conference of Harmonization guidelines to develop a method using the UV-Visible spectroscopy. The method was developed in two solvent systems i.e. methanol and 6.4 pH phosphate buffer with 1.5% polysorbate 80. Methanol solvent was used for the determination of curcumin in the NLC formulation via determining the encapsulation efficiency and 6.4 pH phosphate buffer with 1.5% polysorbate 80 solvent was used for in-vitro and ex-vivo characterization of the developed NLC formulation (cream and gel). These methods were validated in response to linearity, the limit of detection, the limit of quantification, precision, accuracy, repeatability, and specificity.

Lyotropic liquid crystal (LLCs) based drug delivery systems remain in the transitional state of solid and liquid. They are divided into three types: lamellar, cubic, and hexagonal based on the organization. LLCs form compartments on dispersion in the aqueous phase, which can entrap both hydrophilic and lipophilic moieties. The arrangement of lipids, size, and shape can be modified based on water content, lipid concentration, and the additives added to the mixture. The variation in the formulation aspects can be useful to modify the drug release in a controlled manner. The lipids used in LLCs formulation exhibit structural similarities with the skin membrane. These advantages of LLCs formulation favor the efficient delivery of drugs in various skin disorders. The lipophilic nature provides increased permeation, and the bio-adhesive property while the nanosize favors the occlusive nature. The physicochemical properties of LLCs based formulations make it apposite for topical delivery in targeting superficial layers in skin disorders. The review gives insights into LLCs based formulation for the delivery of therapeutics in skin disorders.

The present study elucidates the development of an accurate, precise and simple simultaneous estimation method for the routine analysis of Betamethasone Valerate (BV) and Tazarotene (TZ). This combination is widely used in the treatment of psoriasis. No method has been reported so far for the simultaneous estimation of BV and TZ in topical dosage forms. The method proposed by this study for the quantification of BV and TZ is the Absorption factor method. The developed method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline. The validated method was found to be linear in a concentration range of 10-38 μg/mL and 4-14 μg/mL for BV and TZ respectively with a regression coefficient0.990. The method was validated for accuracy and precision which revealed the recovery of99.80% with RSD2.0. The method was found to be precise with RSD2% for inter and intraday. The developed method was employed for quantification of BV and TZ in lipid based nanocarriers formulation and their in-vitro drug release samples. Further, the developed method was successfully applied for the estimation of BV and TZ in the ex-vivo skin matrix. This showed that the method can sensitively determine the drugs in aqueous and biological samples.