Blood filtering system for COVID-19 management: novel modality of the cytokine storm therapeutics.

The newly emerged coronavirus (SARS-CoV-2) is virulent, contagious, and has rapidly gained many mutations, which makes it highly infectious and swiftly transmissible around the world. SARS-CoV-2 infects people of all ages and targets all body organs and their cellular compartments, starting from the respiratory system, where it shows many deleterious effects, to other tissues and organs. Systemic infection can lead to severe cases that require intensive intervention. Multiple approaches were elaborated, approved, and successfully used in the intervention of the SARS-CoV-2 infection. These approaches range from the utilization of single and/or mixed medications to specialized supportive devices. For critically ill COVID-19 patients with acute respiratory distress syndrome, both extracorporeal membrane oxygenation (ECMO) and hemadsorption are utilized in combination or individually to support and release the etiological factors responsible for the "cytokine storm" underlying this condition. The current report discusses hemadsorption devices that can be used as part of supportive treatment for the COVID-19-associated cytokine storm.

Quality-by-design-based engineered liposomal nanomedicines to treat cancer: an in-depth analysis.

Engineered nano-sized liposomes have attained the highest success rate in commercialization among the reported nanomedicines. However, developing industrially acceptable nanoliposomes is still challenging because the process, formulation factors and even their properties may critically influence the desired attributes of the final nanoliposomal product. Implementation of quality-by-design (QbD) in nanoliposomal fabrication has led to revolutionary advancement int better analysis of the interacting factors (drug and lipid ratio, hydration, sonication, etc), which, in turn, leads to better product performance with predefined attributes (entrapment efficiency percentage, drug release time and pattern, vesicles size, polydispersity index, surface charge and surface morphology). This review provides a summary of decade of research and an in-depth analysis of QbD-based nanoliposomes developed to address different cancers. The review aims to provide complete details of QbD-inspired nanoliposomal development from process to application.

This review describes liposomal nanomedicines manufactured via applying quality-by-design (QbD) principals/methods for the treatment of cancer. QbD is industrially applicable technique of manufacturing for emerging pharmaceutical nano-formulations owing to its benefits, including reduced cost, a smaller number of trials, high risk assessment and control over different formulation factors.

'Transfersome-embedded-gel' for dual-mechanistic delivery of anti-psoriatic drugs to dermal lymphocytes.

AIM: Develop a platform for co-delivering clobetasol propionate (CP) and cyclosporine (CyA) to the epidermis and dermis to treat psoriasis. METHODS: The transfersomes were prepared by thin-film hydration method. Transfersomes were characterised by dynamic light scattering and transmission electron microscope (TEM). Then, the gel stability, viscosity, pH, and spreadability were measured. Cytotoxicity of the CyA-loaded transfersome embedded in CP-dispersed gel (TEG-CyA-CP) was assessed on both human keratinocyte cell line (HaCaT) and Jurkat cells. In vitro cellular uptake and ex vivo dermal distribution was measured. The expression of inflammatory markers was assessed by reverse-transcription PCR (RT-PCR). RESULTS: Nanoscale (<150 nm) transferosomes with high CyA encapsulation efficiency (>86%) were made. TEG-CyA-CP demonstrated higher viscosity (4808.8 ± 12.01 mPas), which may help control dual drug release. Ex vivo results showed TEG-CyA-CP ability to deliver CyA in the dermis and CP in the epidermis. RT-PCR studies showed the optimised formulation helps reduce the tumour necrosis factor (TNF-α) and interleukin-1 (IL-1) levels to relieve psoriasis symptoms. CONCLUSION: The developed TEG-CyA-CP represents a promising fit-to-purpose delivery platform for the dual-site co-delivery of CyA and CP in treating psoriasis.

Laser activatable nanographene colloids for chemo-photothermal combined gene therapy of triple-negative breast cancer.

This investigation reports the green approach for developing laser activatable nanoscale-graphene colloids (nGC-CO-FA) for chemo-photothermal combined gene therapy of triple-negative breast cancer (TNBC). The nano colloid was found to be nanometric as characterized by SEM, AFM, and zeta sizer (68.2 ± 2.1 nm; 13.8 ± 1.2 mV). The doxorubicin (Dox) loaded employing hydrophobic interaction/π-π stacking showed >80% entrapment efficiency with a sustained pH-dependent drug release profile. It can efficiently incorporate siRNA and Dox and successfully co-localize them inside TNBC cells to obtain significant anticancer activity as evaluated using CCK-8 assay, apoptosis assay, cell cycle analysis, cellular uptake, fluorescence assay, endosomal escape study, DNA content analysis, and gene silencing efficacy studies. nGC-CO-FA/Dox/siRNA released the Dox in temperature- and a pH-responsive manner following NIR-808 laser irradiation. The synergistic photo-chemo-gene therapy using near infrared-808 nm laser (NIR-808) irradiation was found to be more effective as compared to without NIR-808 laser-treated counterparts (∆T: 37 ± 1.1 °C → to 49.2 ± 3.1 °C; 10 min; 0.5 W/cm2), suggesting the pivotal role of photothermal combined gene-therapy in the treatment of TNBC.

Engineered nanoplex mediated targeted miRNA delivery to rescue dying podocytes in diabetic nephropathy.

MicroRNAs (miRNA) is vital for gene expression regulation and normal kidney function. Mainly, miRNA-30a is responsible for the homeostasis of podocytes. In the diabetic nephropathic condition, miRNA-30a is directly and primarily suppressed by hyperglycemic kidney induced Notch signaling pathway leads to podocyte damage and apoptosis. Thus, transferring the exogenous miRNA-30a to podocytes might improve albuminuria as well as podocytes injury. The deprived stability, poor targetability, and low specificity in vivo are critical limitations to attain this objective. This investigation reports the specific and efficient delivery of miRNA-30a mimic via cyclo(RGDfC)-gated polymeric-nanoplexes with dendrimer templates to alleviate podocyte conditions. The nanoplexes able to protect RNase enzyme and to exhibit greater cellular uptake viaαvß3 receptor selective binding in HG treated podocytes. The nanoplexes up-regulated the expression level of miRNA-30a and repress the elevated Notch-1 signaling in HG exposed podocytes. The critical results of in vivo experimentation attribute marked suppression of Notch-1 in streptozotocin (STZ) induced diabetic C57BL/6 mice and reduced glomerular expansion and fibrosis in the glomerular area. Developed nanoplexes represents an efficient platform for the targeted delivery of exogenous miRNA to podocytes. The approach developed herein could be extrapolated to other gene therapeutics and other kidney-related diseases.

Multifunctional polymeric micellar nanomedicine in the diagnosis and treatment of cancer.

Polymeric micelles are a prevalent topic of research for the past decade, especially concerning their fitting ability to deliver drug and diagnostic agents. This delivery system offers outstanding advantages, such as biocompatibility, high loading efficiency, water-solubility, and good stability in biological fluids, to name a few. The multifunctional polymeric micellar architect offers the added capability to adapt its surface to meet the looked-for clinical needs. This review cross-talks the recent reports, proof-of-concept studies, patents, and clinical trials that utilize polymeric micellar family architectures concerning cancer targeted delivery of anticancer drugs, gene therapeutics, and diagnostic agents. The manuscript also expounds on the underlying opportunities, allied challenges, and ways to resolve their bench-to-bedside translation for allied clinical applications.

Cyclo-RGD Truncated Polymeric Nanoconstruct with Dendrimeric Templates for Targeted HDAC4 Gene Silencing in a Diabetic Nephropathy Mouse Model.

Diabetic nephropathy (DN), a chronic progressive kidney disease, is a significant complication of diabetes mellitus. Dysregulation of the histone deacetylases (HDACs) gene has been implicated in the pathogenesis of DN. Hence, the HDAC-inhibitors have emerged as a critical class of therapeutic agents in DN; however, the currently available HDAC4-inhibitors are mostly nonselective in nature as well as inhibit multiple HDACs. RNA interference of HDAC4 (HDAC4 siRNA) has shown immense promise, but the clinical translation has been impeded due to lack of a targeted, specific, and in vivo applicable delivery modality. In the present investigation, we examined Cyclo(RGDfC) (cRGD) truncated polymeric nanoplex with dendrimeric templates for targeted HDAC4 Gene Silencing. The developed nanoplex exhibited enhanced encapsulation of siRNA and offered superior protection against serum RNase nucleases degradation. The nanoplex was tested on podocytes (in vitro), wherein it showed selective binding to the αvß3 integrin receptor, active cellular uptake, and significant in vitro gene silencing. The in vivo experiments showed remarkable suppression of the HDAC4 and inhibition in the progression of renal fibrosis in the Streptozotocin (STZ) induced DN C57BL/6 mice model. Histopathological and toxicological studies revealed nonsignificant abnormality/toxicity with the nanoplex. Conclusively, nanoplex was found as a promising tactic for targeted therapy of podocytes and could be extended for other kidney-related ailments.

Green graphene nanoplates for combined photo-chemo-thermal therapy of triple-negative breast cancer.

Aim: Green graphene oxide (GO) nanoplates, which are reduced and stabilized by quercetin and guided by folate receptors (quercetin reduced and loaded GO nanoparticles-folic acid [FA]), were developed to mediate combined photo-chemo-thermal therapy of triple-negative breast cancer. Materials & methods: Modified Hummers method was used for the synthesis of GO followed by its reduction using quercetin, FA was then conjugated as a targeting ligand. A cytotoxicity assay, apoptosis assay and cellular uptake assay were performed in vitro in MDA-MB-231 cell line with and without irradiation of a near-infrared 808 nm laser. Results & conclusion: Quercetin reduced and loaded GO nanoparticles-FA showed significantly high cellular uptake (p < 0.001) and cytotoxic effects in MDA-MB-231 cells, which was even more prominent under the situation of near-infrared 808 nm laser irradiation, making it a potential option for treating triple-negative breast cancer.

Understanding molecular upsets in diabetic nephropathy to identify novel targets and treatment opportunities.

Diabetes and related complications are becoming a global encumbrance. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). The available therapeutic modalities related to DN do not treat DN at the molecular level, proposing further amendments in the management of DN based on the pathogenesis of DN. This manuscript discusses the concept and applications of nanomedicine for the treatment of DN that can improve renal targeting, retention and localization. This review also highlights the current issues related to targeting DN, challenges and allied opportunities toward the development of next-generation drugs and treatments for the management of DN.

Method and its Composition for encapsulation, stabilization, and delivery of siRNA in Anionic polymeric nanoplex: An In vitro- In vivo Assessment.

Small interfering RNA (siRNA) are synthetic RNA duplex designed to specifically knockdown the abnormal gene to treat a disease at cellular and molecular levels. In spite of their high potency, specificity, and therapeutic potential, the full-fledged utility of siRNA is predominantly limited to in vitro set-up. Till date, Onpattro is the only USFDA approved siRNA therapeutics available in the clinic. The lack of a reliable in vivo siRNA delivery carrier remains a foremost obstacle towards the clinical translation of siRNA therapeutics. To address the obstacles associated with siRNA delivery, we tested a dendrimer-templated polymeric approach involving a USFDA approved carrier (albumin) for in vitro as well as in vivo delivery of siRNA. The developed approach is simple in application, enhances the serum stability, avoids in vivo RNase-degradation and mediates cytosolic delivery of siRNA following the endosomal escape process. The successful in vitro and in vivo delivery of siRNA, as well as targeted gene knockdown potential, was demonstrated by HDAC4 inhibition in vitro diabetic nephropathy (DN) podocyte model as well as in vivo DN C57BL/6 mice model. The developed approach has been tested using HDAC4 siRNA as a model therapeutics, while the application can also be extended to other gene therapeutics including micro RNA (miRNA), plasmids oligonucleotides, etc.

Effect of the pH in the enrichment of X or Y sex chromosome-bearing sperm in bovine.

BACKGROUND AND AIM: Studies have shown that the pH of the vagina during the course of fertilization may influence the migration of X- and Y-bearing spermatozoa and thus leading to skewness in the sex of the offspring. Hence, this study was carried out to check the effect of the pH in the enrichment of X or Y sex chromosome-bearing sperm in bovine (Bos indicus). MATERIALS AND METHODS: To check the effect of pH in the enrichment of X or Y sex chromosome-bearing sperm in bovine, we used buffers of various pH ranging from 5.5 to 9.0 for swim-up procedure of sperm sample and collected upper and bottom fraction from the same buffer and checked the abundance of X- and Y-bearing spermatozoa by droplet digital polymerase chain reaction using X- and Y-chromosome-specific DNA probe. RESULTS: The abundance of X- and Y-bearing spermatozoa was not differed significantly in either of the fraction collected. CONCLUSION: Thus, it appears to be unlikely that an immediate impact of pH on sperm can be a solitary impact on the sex of offspring in bovine.

Dendrimer grafted albumin nanoparticles for the treatment of post cerebral stroke damages: A proof of concept study.

Stroke is the second largest disease of mortality. The biggest hurdle in designing effective brain drug delivery systems is offered by the blood-brain barrier (BBB), which is highly impermeable to many drugs. Albumin nanoparticles (NP) have gained attention due to their multiple ligand binding sites and long circulatory half-life. Citicoline (CIT) is reported to enhance the acetylcholine secretion in the brain and also helps in membrane repair and regeneration. However, the poor BBB permeation of CIT results in lower levels of CIT in the brain. This demands the development of a suitable delivery platform to completely realize the therapeutic benefit of CIT in stroke therapy. This investigation reports the synthesis and characterization of second generation (2.0 G) dendrimer Amplified Albumin (dAA) biopolymer by FTIR, MALDI-TOF, and surface charge (mV). Further, the synthesized biopolymer has been utilized to develop a CIT nanoformulation using a commercially translatable one-pot process. Release of CIT from biopolymer was performed within an acetate buffer at pH 5 and Phosphate buffer at pH 7.4. Further, we investigated the ability of biopolymer to permeate BBB by in vitro permeability assay in bEnd.3 cells. MTT assay of CIT-dAA-NP, CIT-ANP, and 2.0 G PAMAM dendrimers was performed in bEnd.3 cells. Therapeutic efficacy of the synthesized biopolymer was determined by VEGF gene expression within an in vitro hypoxia model in PC12 cells. Thus, this investigation resulted in biopolymers that can be used to deliver any therapeutic agent by altering the permeability of the BBB. Also, cationization by dendrimer grafting is one such strategy that may be used to cationize any other negatively charged polymer, such as albumin. The synthesized biopolymer is not limited to deliver molecules to the brain, but can also be used to increase the loading of negatively-charged drug molecules, siRNA, or any other oligonucleotide.

Fabrication of Mucoadhesive-Dendrimers as Solid Dosage Forms.

Mucoadhesion has a potential role in the delivery of pharmaceutical medicaments via various routes of administration, viz. oral, nasal, vaginal, and buccal. Mucoadhesion provides controlled drug delivery, sustained drug delivery, and local or site-specific drug delivery. This chapter focuses on the mechanism of bio-adhesion to glycoprotein layer of mucosal membrane. Some of the gastric mucoadhesive solid dosage forms of nanocarrier, viz. nanoparticle, microsphere, and nanofibers, undergo evaluation of mucoadhesive parameters. That includes mucoadhesive strength, tensile strength, swelling index, stability studies, in vivo study, etc. The oral route is the most desirable way among intravenous, subcutaneous, intramuscular, intranasal, intravaginal, etc. for drug delivery and because of patient compliance. One of the novel approaches is where nanocarrier is loaded in the solid dosage form for effective drug action and enhanced local delivery of a drug. Mainly this chapter explains about dendrimer-based oral solid dosage form (tablet) employing mucoadhesive polymers with an aim to improve retention time of drug at desired sites. Dendrimer-loaded mucoadhesive tablets promise controlled drug delivery with a gastro-retentive property, higher drug incorporation, ease of formulation development, and accessible absorption, owing to adjacent interaction with a biological membrane and prolonged retention to mucosa providing higher bioavailability of drugs.

Surface Modification of Biomedically Essential Nanoparticles Employing Polymer Coating.

Colloidal nanoparticles offering multiple biological applications carry tremendous potential to be developed as future medicines or nanomedicines. However, to decrease the particle agglomeration and enhance the stability of nanoparticles, functionalization could be of great interest. Functionalization is also capable of molding the delivery system for targeting and selective delivery of drugs and other biomolecules. In particular, the control over the size and the surface chemistry is crucial, since the successful applications in the prevention of diseases required biocompatibility at biological interfaces. Regardless of the advancements noted in nanotechnology-based nanoparticles, the development of nontoxic/biocompatible multi-functionalized nanoparticles is still a critical problem for researchers and requires urgent attention. In this chapter, an overview of nanoparticle functionalization with particular emphasis on its principle, needs, and formulation strategies has been discussed. Moreover, various applications of different surface-functionalized nanoparticles such as gold, silver, silicon, magnetic, liposomes, dendrimers, poly-lactic-co-glycolic acid, and solid lipid nanoparticles have also been presented.

Nanogold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynamic- therapy of rheumatoid arthritis.

This investigation reports a novel nanoGold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynamic- therapy of rheumatoid arthritis (RA). Architecturally, the nanocomposites comprised of a nanoGold (Au) at the focal whose surface is functionalized by hydroxy-terminated thiolated-dendrons following Au-thiol bond formation to produce nanoGold-core multifunctional dendrimer (Au-DEN). The surface hydroxyl groups of Au-DEN were then conjugated with methotrexate (MTX; a disease-modifying first line anti-rheumatic drug; DMARD; 74.29 ±â€¯0.48% loading) to form Au-DEN-MTX-NPs (Particle size: 100.15 ±â€¯28.36 nm; poly dispersibility index, PDI: 0.39 ±â€¯0.02; surface zeta potential, ζ: -22.45 ±â€¯1.06 mV). MTX was strategically selected to serve as an anti-rheumatic DMARD as well as a targeting ligand to attain selective localization of the formulation in arthritic tissue via folate receptors upregulated on arthritic tissues. The docking study was performed to confirm the viable binding efficiency of MTX towards ß-folate receptors that are overexpressed on arthritic tissues taking folic acid as a reference standard. The IR780, a NIR active bioactive was also loaded in Au-DEN-MTX NPs to offer photothermal benefit upon irradiation with NIR laser (wavelength: 808 nm). The hypothesis was tested by elucidation of in vitro drug release profile, photothermal activity, cellular uptake (Fluorescence and confocal laser scanning microscopy; CLSM), cell viability assay (MTT protocol) and Intracellular reactive oxygen species (ROS) generation in mouse macrophage RAW264.7 cells and Lipopolysaccharide (LPS) activated RAW264.7 cells. Furthermore, the hemolytic toxicity and stability studies were also investigated to determine the blood compatibility as well as ideal storage condition of NPs. The outcome of this investigations presents developed multifunctional targeted NPs to be potential therapeutics for the improved treatment of RA. The approach can also be applied to other clinical interventions involving countering inflammatory conditions.

Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer.

In tumorous tissues, the absence of vasculature supportive tissues intimates the formation of leaky vessels and pores (100 nm to 2 µm in diameter) and the poor lymphatic system offers great opportunity to treat cancer and the phenomenon is known as Enhanced permeability and retention (EPR) effect. The trends in treating cancer by making use of EPR effect is increasing day by day and generate multitudes of possibility to design novel anticancer therapeutics. This review aimed to present various factors affecting the EPR effect along with important things to know about EPR effect such as tumor perfusion, lymphatic function, interstitial penetration, vascular permeability, nanoparticle retention etc. This manuscript expounds the current advances and cross-talks the developments made in the of EPR effect-based therapeutics in cancer therapy along with a transactional view of its current clinical and industrial aspects.

Insight into bovine (Bos indicus) spermatozoal whole transcriptome profile.

Mature spermatozoa harbor both coding and non-coding type of RNAs which regulates spermatogenesis, fertilization and early development. Characterization of bovine sperm transcriptome can provide more insight into the molecular mechanisms involved in these processes. Here, we have analyzed whole transcriptome profile of Bos indicus spermatozoa to access the global RNA expression. RNA-Seq analysis identified 14,306 genes expressed with FPKM >0, while 405 genes expressed when threshold increased to FPKM >5. Functional annotations showed that sperm transcripts were associated with molecular processes (translation, ribosomal small and large subunit assembly) and cellular components (cytosolic small and large ribosomal subunit and membranes) related to known sperm functions at fertilization and spermatogenesis. The RNA-Seq data was validated using droplet digital PCR where both highly abundant gene viz. RN7SL1 and less abundant gene viz. ZFP280B were validated. This study may provide future directions in reproductive biology of Bos indicus.

'Dendrimer-Cationized-Albumin' encrusted polymeric nanoparticle improves BBB penetration and anticancer activity of doxorubicin.

Glioblastoma is one of the most rapaciously growing cancer within the brain with an average lifespan of 12-15 months (5-year survival <3-4%). Doxorubicin (DOX) is clinically utilized as a first line drug in the treatment of Glioblastoma, however, its restricted entry into the brain via the blood-brain barrier (BBB), limited blood-tumor barrier (BTB) permeability, hemotoxicity, short mean half-life of 1-3 hr as well as rapid body clearance results in tremendously diminished bioactivity in glioblastoma. Dendrimer-Cationized-Albumin (dCatAlb) was synthesized following the carboxyl activation technique and the synthesized biopolymer was characterized by FTIR, MALDI-TOF and zeta potential. The prepared dCatAlb was encrusted on DOX-loaded PLGA nanoparticle core to develop a novel hybrid DOX nanoformulation (dCatAlb-pDNP; particle size: 156 ±â€¯10.85 nm; ƺ: -10.0 ±â€¯2.1 mV surface charge). The formulated dCatAlb-pDNP showed a unique pH-dependent DOX release profile, diminished hemolytic toxicity, higher drug uptake (<0.001) and cytotoxicity in U87MG glioblastoma cells, increase levels of caspase-3 gene in U87MG cells (approximately 5.35-fold higher) inferred that anticancer activity is primarily taking place through caspase-mediated apoptosis mechanism. The developed novel DOX nanoformulation also showed superior trans-epithelial permeation transport across monolayer bEnd.3 cells as well as notable biocompatibility and stability. The dCatAlb-pDNP showed enhanced BBB permeation efficacy as confirmed permeation assay in bEnd.3 cell-based model. The long-term formulation stability of developed nanoformulations was studied by storing them at 5 ±â€¯2 °C and 30 ±â€¯2 °C/60 ±â€¯5% Relative Humidity (% RH) in the stability chamber for a period of 60 days (ICHQ1A (R2)). The outcomes of this investigation evidently indicate that dCatAlb-pDNP offers superior anticancer activity of DOX in glioblastoma cells while significantly improving its BBB permeation. The developed formulation is a biocompatible, safer and commercially viable approach to delivering DOX selectively in sustained manner glioblastoma while countering its hemolytic toxic effect, which is a major ongoing issue with conventional DOX injectable available in the market today.

Carbon nanotubes in the delivery of anticancer herbal drugs.

Cancer is estimated to be a significant health problem of the 21st century. The situation gets even tougher when it comes to its treatment using chemotherapy employing synthetic anticancer molecules with numerous side effects. Recently, there has been a paradigm shift toward the adoption of herbal drugs for the treatment of cancer. In this context, a suitable delivery system is principally warranted to deliver these herbal biomolecules specifically at the tumorous site. To achieve this goal, carbon nanotubes (CNTs) have been widely explored to deliver anticancer herbal molecules with improved therapeutic efficacy and safety. This review uniquely expounds the biopharmaceutical, clinical and safety aspects of different anticancer herbal drugs delivered through CNTs with a cross-talk on their outcomes. This review will serve as a one-stop-shop for the readers on various anticancer herbal drugs delivered through CNTs as a futuristic delivery device.

Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential.

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.