Pulmonary administration of cross-linked chitosan nanoparticles of genistein for regulating blood glucose.

The research study focused on the development and characterization of sustained release formulation of genistein (GEN)-loaded chitosan (CS) nanoparticles to deliver in the form of dry powder inhaler (DPI) via pulmonary route to offer higher stability and anti-diabetic activity. The GEN-loaded nanoparticles were prepared by cross-linking reaction of CS and sodium hexametaphosphate (SHMP). The optimized formulation displayed particle size (PS) of 684.2 ± 26.5 nm, zeta potential (ZP) of 19.6 ± 4.50 mV, % entrapment efficiency (% EE) of 87.33 ± 8.46 % and drug release profile of 85.48 ± 5.50 % for 48 h. The in-vivo studies exhibited a superior sustained release formulation of GEN in the regulation of blood glucose levels (BGLs). The powder showed the emitted fraction (EF) of 86.76 % and effective inhalation index (EI) of 85.41 %. The reduction of BGLs (85 %) was observed in the diabetic group. This might be due to the inhibition of proliferation of pancreatic ß-cells (growth factor inhibition targeting cAMP and ERK1/2 pathway), antioxidative activity, reducing insulin resistance, and the adipose tissue mass and alteration of the hepatic glucose metabolism. Hence, these results proved the delivery of GEN in the form of DPI system as a favorable route for treating type-1 diabetes mellitus with a longer duration of action.

Central composite design augmented quality-by-design-based systematic formulation of erlotinib hydrochloride-loaded chitosan-poly (lactic-co-glycolic acid) nanoparticles.

Aim: This study aimed to formulate erlotinib hydrochloride (ERT-HCL)-loaded chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using Quality-by-Design (QbD) to optimize critical quality attributes (CQAs). Materials & methods: Quality target product profile (QTPP) and CQAs were initially established. Based on L8-Taguchi screening and risk assessments, central composite design (CCD) design was used to optimize NPs. Results: ERT-HCL-loaded CS-PLGA NPs had a mean particle diameter, zeta potential and entrapment efficiency of 226.50 ± 1.62 d.nm, 27.66 ± 0.64 mV and 78.93 ± 1.94 %w/w, respectively. The NPs exhibited homogenous spherical morphology and sustained release for 72 h. Conclusion: Using systematic QbD approach, ERT-HCL was encapsulated in CS-PLGA NPs, optimizing CQAs. These findings propel future research for improved NSCLC treatment.

Innovative erlotinib-loaded chitosan-PLGA nanoparticles, developed through a systematic QbD approach, promise enhanced drug delivery for NSCLC. Optimized for size, potential and entrapment efficiency, these particles demonstrate sustained release over 72 h. #DrugDelivery #QBD #NSCLC.

Nanodiamond-based berberine aquasomes for enhancing penetration across epidermis to treat psoriasis.

The use of berberine hydrochloride (BCS class III) has limited application in psoriasis, when given as topical drug delivery systems, due to low permeability in the skin layer. Hence, berberine hydrochloride-loaded aquasome nanocarriers were developed for skin targeting, particularly epidermis (primary site of psoriasis pathophysiology) and enhance the skin permeability of berberine hydrochloride. Aquasomes were formulated using the adsorption method and characterized by structural morphology TEM, % drug adsorption, drug release profile (in-vitro and ex-vivo), in-vivo efficacy study and stability study. The reduced particle size and higher surface charge of SKF3 formulation (263.57 ± 27.78 nm and -21.0 ± 0.43 mV) showed improved stability of aquasomes because of the development of higher surface resistance to formation of aggregates. The adsorption of hydrophilic berberine and the non-lipidic nature of aquasomes resulted in % adsorption efficiency (%AE) of 94.46 ± 0.39 %. The controlled first-order release behavior of aquasomes was reported to be 52.647 ± 14.63 and 32.08 ± 12.78 % in in-vitro and ex-vivo studies, respectively. In-vivo studies demonstrated that topical application of berberine hydrochloride loaded aquasomes significantly alleviated psoriasis symptoms like hyperkeratosis, scaling and inflammation, due to the reduction in the inflammatory cytokines (IL-17 and IL-23). Therefore, aquasome formulation exhibits an innovative approach for targeted application of berberine hydrochloride in the management of psoriasis.

Potentiation of Brain Bioavailability Using Thermoreversible Cubosomal Formulation.

The aim of the present study was to develop and evaluate intranasal formulations of the thermoreversible fluoxetine cubosomal in situ gel. This gel was intended for permeation and bioavailability enhancement to target the brain effectively by bypassing the blood-brain barrier (BBB). Fluoxetine-loaded cubosomes were prepared by the homogenization method followed by the cold method approach to develop in situ gel. Fluoxetine-loaded cubosomes displayed a higher encapsulation efficiency (82.60 ± 1.25%) than fluoxetine. This might be due to the solubilizing activity of the polymer to cause partitioning of the lipophilic drug into the aqueous phase during the change from the cubic gel phase to cubosomes. In vitro analysis of fluoxetine-loaded cubosomal in situ gel showed a sustained release profile (93.22 ± 2.47%) due to limited diffusion of fluoxetine. The formation of strong affinity bonds of the drug with GMO (drug transporter) decreased the drug release in comparison to that with fluoxetine-loaded cubosomes (90.68 ± 1.74%). The ex vivo drug release profile revealed the drug release of 96.31 ± 2.88% by the end of 24 h. This is attributed to the higher capability of the intranasal cubosomal in situ gel to prolong the retention and enable better permeation through the nasal mucosa. In male Wistar rats, in vivo biodistribution studies for cubosomal in situ gel administered via the intranasal route at a dose of 3.5 mg/kg demonstrated an increase in pharmacokinetic parameters like the AUC (406 ± 75.35 µg/mL), Cmax (368.07 ± 0.23 µg/mL), Tmax (4 h), and t1/2 (14.06 h). The mucoadhesive nature of the in situ gel led to an increase in the residence time of the gel in the nasal mucosa. The biodistribution study of intranasal in situ cubosomal gel improved the bioavailability 2.21-fold in comparison to that with the cubosomal dispersion but 2.83-fold in comparison to that with the drug solution. Therefore, fluoxetine-loaded cubosomal in situ gel proved as a promising carrier for effective transportation of fluoxetine via the intranasal route with significant brain bioavailability.

Competitive inhibition of nicotine acetylcholine receptors using microneedles of nicotine and varenicline for smoking withdrawal therapy.

Current strategies for smoking withdrawal conditions involve monotherapy of nicotine and combinational therapy of nicotine with varenicline or bupropion as per the CDC and FDA. The available dosage forms for nicotine are patches, gums, inhalers and nasal sprays, bupropion and varenicline are available in tablet form. This research work focused on developing a microneedle delivery system to deliver combination drug for overcoming the obstacles encountered by oral route of administration of varenicline such as severe side effects (mood swings, agitation, depressed behaviour, seizures, etc), and nicotine therapy challenges such as short half-life, repeated dosing, nausea, and vomiting. The nanoparticles of nicotine prepared by nanoprecipitation method showed particle size PTZ (356.6 ± 65.98), percentage entrapment efficiency (35.55 % ± 0.007), in-vitro drug release (47.89 % ± 0.7) for 72 h. Microneedles showed height (600 µm), width (350 µm), and tip diameter (10 µm). The nanoparticles encapsulated in microneedles showed in-vitro sustained delivery of nicotine (67.00 % ± 4.92) and varenicline (79.78 % ± 1.09) in 48 h. Nicotine released in a sustained manner attaches to the nicotine acetylcholine receptors (nAchR) to release dopamine for controlling the withdrawal challenges such as anxiety, irritability, cravings, disturbed sleep pattern, etc. The varenicline released from microneedles binds to the nAchR and inhibits dopamine release responsible for the euphoric effect induced by nicotine, and thus assists in curbing the nicotine withdrawal symptoms. This combination microneedle system offers prolonged treatment in a single application for smoking withdrawal conditions wherein patients are not in stage of oral dosing because of repeated dosing resulting in adverse effects like seizures, hypertension, sleep disturbances, insomnia, and nausea.

Bimatoprost-loaded lipidic nanoformulation development using quality by design: liposomes versus solid lipid nanoparticles in intraocular pressure reduction.

Background: Bimatoprost is a drug used to lower intraocular pressure in the treatment of glaucoma. Conventional eye drops have the limitations of repeated dosing, drug loss due to tear outflow and hence poor availability for action. Materials & methods: Using a systematic quality by design approach, liposomes and solid lipid nanoparticles were formulated and further encapsulated in thermo-sensitive in situ hydrogel. Results & conclusion: Optimized liposomes had 87.04% encapsulation efficiency and 306.78 nm mean particle size, while solid lipid nanoparticles had 90.51% and 304.21 nm. Bimatoprost liposomes had controlled zero-order drug kinetics and no initial burst release, making them better than solid lipid nanoparticles. Bimatoprost-loaded liposomes in thermo-sensitive hydrogel decreased intraocular pressure for 18 h.

Fragmented antibodies in non-small cell lung cancer: A novel nano-engineered delivery system for detection and treatment of cancer.

Non-small cell lung cancer (NSCLC) has a long history of defying traditional cytotoxic treatment. Significant advancements in biotechnology, cancer biology, and immunotherapy have provided new insights that have altered the landscape for the management of NSCLC, clearing the way for a new era of pharmaceuticals in the form of monoclonal antibodies and their fragments. Antibody fragments are superior to monoclonal antibodies because of their small size, which allows them to penetrate cells and tissues effectively. When combined with functional nanocarriers, antibody fragments can target cancer cells while offering improved efficacy and fewer off-target effects. We discuss current topics of interest including anti-CTLA-4 mAbs, Talactoferrin alfa (TLF), and the CYFRA 21-1 biomarker, with brief insights into its novel detection system.

Design and Characterization of Nanoflowers-based Biosensor for Estimation of Bilirubin in Jaundice.

Nanoflowers (NFs) are flower-shaped nanoparticulate systems with a higher surface-to-volume ratio and good surface adsorption. Jaundice indicates yellow discoloration of skin, sclera, and mucus membrane and is a clinical indication of bilirubin accumulation in the blood which occurs as a consequence of the incapability of the liver to excrete bilirubin in the biliary tree or conjugate bilirubin and higher production of bilirubin in the body. Several methods have been developed so far for bilirubin estimation in jaundice like the spectrophotometric method, chemiluminescence method, etc., but biosensing methods provide advantages over traditional methods concerning the surface area, adsorption, particle size, and functional characteristics. The primary objective of the present research project was to formulate and examine the adsorbent nanoflowers-based biosensor for accurate, precise, and sensitive detection of bilirubin in jaundice. The particle size of adsorbent nanoflowers was found to be in the range of 300-600nm with the surface charge (zeta potential) in the range of -1.12 to -15.42 mV. Transmission electron microscopy and scanning electron microscopy images confirmed the flower-like morphological structure of adsorbent NFs. The adsorption efficiency of NFs for bilirubin adsorption was maximum at 94.13%. Comparative studies of bilirubin estimation in the pathological sample with adsorbent NFs and diagnostic kit displayed bilirubin concentration to be 1.0 mg/dL in adsorbent nanoflowers and 1.1 mg/dL with diagnostic kit indicating effective detection of bilirubin with adsorbent NFs. The nanoflower-based biosensor acts as a smart approach to elevate adsorption efficiency on the surface of nanoflower due to a higher surface-to-volume (SV) ratio. Graphical Abstract.

Banana Peel Waste: An Emerging Cellulosic Material to Extract Nanocrystalline Cellulose.

Nanocrystalline cellulose (NCC) has gained attention due to its versatile properties such as biocompatibility, sustainability, high aspect ratio, and abundance of -OH groups that favor modifications of NCC. The objective of this paper is to develop NCC by extracting and characterizing NCC prepared from banana peel powder (BPP). BPP was subjected to alkali and bleaching treatment to remove lignin and hemicellulose and then subjected to acid hydrolysis to prepare NCC. Under optimal conditions (200 mL of sulfuric acid 55% v/v at 50 °C for 60 min), the NCC yield was found to be 29.9%. The particle size and zeta potential of the NCC were found to be 209 nm and -43 mV, respectively. Attenuated total reflectance Fourier transform infrared spectroscopy showed successful removal of lignin and hemicellulose from BPP after the alkali treatment, bleaching, and acid hydrolysis. Field emission scanning electron microscopy showed needle-shaped crystals and transmission electron microscopy showed particles in the nano range. X-ray diffraction analysis showed that the crystallinity index of NCC was 64.12% while keeping the cellulose I crystal structure intact. Thermogravimetric analysis showed good stability which paves way for NCC to be explored for various applications. All the parameters evaluated indicated that NCC was successfully prepared from BPP using alkali treatment, bleaching, and acid hydrolysis.

Biodegradable Polymer-Based Microspheres for Depot Injection-Industry Perception.

The discovery of proteins and peptides marked the actual beginning for pharmaceutical companies to do research on novel delivery systems for delivering these therapeutic proteins. Biodegradable polymer-based microspheres for controlled-release depot injection are known for decades and have proved to be one of the best possible approaches. Despite being known for decades, the commercial success of microsphere-based delivery systems remains limited. Very few products are seen in the market with no generics available for approved brand products whose patents have either expired or are about to expire. All this points to the complexities involved in developing these delivery systems. Still, many hurdles remain in developing these drug delivery systems namely, poor drug entrapment, unwanted burst release, poor in vitro in vivo correlation, lack of proper in vitro testing methods, problems involved during scale-up, and the most important hurdle being sterilization of the product. To achieve successful product development, all of these technical difficulties need to be simultaneously dealt with and resolved. This article attempts to highlight the problem areas for these delivery systems along with the regulatory requirements involved and map the present status of these delivery systems.

Aquasomes: Advanced Vesicular-based Nanocarrier Systems.

BACKGROUND: Aquasomes are novel trilayered non-lipoidal vesicular nanocarriers that demonstrate structural similarity to ceramic nanoparticles with theranostic activity for diseases like ovarian cancer and antigen delivery. OBJECTIVE: The objective of the present article is to highlight the multifaceted potential of aquasomes over other nanocarriers for the treatment of various treatments like hemophilia A, cancer, and hepatitis. METHODS: Aquasomes enter the target cell by modifying the surface chemistry, extending drug release. The solid core of aquasomes provides structural stability whereas their oligomeric coatings protect drugs from dehydration. This vesicular delivery system was successfully utilized for the delivery of acid-labile enzymes, antigens, vaccines, etc. The aquasomes nanocarrier exhibits a larger surface area, volume, and mass ratio that allows the drug to penetrate inside the cells and a prolonged drug release profile. Moreover, aquasomes consist of a high mechanical strength, reduced or no biodegradability during storage, and a good body response that facilitates deeper penetration into capillaries which makes them more special and interesting. RESULTS: Aquasomes are a potential alternative over other nanocarriers for insulin, antigen, and oxygen delivery. CONCLUSION: In the near future, aquasomes-based nano-drug delivery systems can be a fascinating field for research in nanotechnology.

Non-oral routes, novel formulations and devices of contraceptives: An update.

Family planning enables society to prevent unintended pregnancies and helps in attaining desired spacing between the pregnancies. It is done with the use of contraceptive methods and infertility treatments. The use of contraceptives serves to ease maternal ill-health and reduce pregnancy-related deaths and helps to decrease the number of unsafe abortions and HIV transmission from mothers to newborns. The most popular contraception method is a daily dose of combined oral contraceptives pills. However, poor compliance and various adverse effects are common problems of oral contraceptives that considerably reduce their long-term use. Thus, several non-oral contraceptive options have been developed for better compliance, reduced side effects and improved therapeutic efficacy. This review presented the non-oral contraceptive formulations given by different routes such as transdermal, nasal, subcutaneous, intramuscular, intrauterine and vaginal routes. These formulations delivering contraceptives, mainly through devices, include transdermal patches and microneedles, nasal sprays, intrauterine devices and intrauterine systems, vaginal rings, contraceptive implants and contraceptive injections, which are unique in their specific advantages and drawbacks.

Adsorption of Cisplatin on Oxidized Graphene Nanoribbons for Improving the Uptake in Non-small Cell Lung Carcinoma Cell Line A549.

BACKGROUND: Graphene nanoribbons are nanosized strips of graphene with unique physicochemical properties like higher drug loading capacity and affinity for tumor cells. OBJECTIVE: The principal objective of this research was to develop oxidized graphene nanoribbons (O-GNRs)-based delivery system for cisplatin against non-small cell lung carcinoma cell line A549 by selective endocytosis. METHODS: The O-GNRs prepared using various synthetic steps like oxidative unzipping were evaluated for various parameters like morphology, Fourier Transform Infrared (FTIR) study, % adsorption efficacy, Differential scanning colometric (DSC) study and in-vitro efficacy studies. RESULTS: Graphene nanoribbons with the length of 200-250 nm and width of 20-40 nm were obtained. The FTIR spectrum of drug-loaded O-GNRs exhibited a characteristic peak at 1550 cm-1 (- N-H group) of cisplatin. The DSC indicated the presence of sharp endothermic peaks at 59°C (PEG), 254°C (-C-NH3) and 308.6°C (-C-Pt). The % adsorption efficiency was found to be 74.56 ± 0.798% with in-vitro release in controlled manner (63.36% ± 0.489%) for 24 h. CONCLUSION: The nanoformulation showed an average inhibition of 22.72% at a lower dose of cisplatin (> 25%) by passive targeting on cell line A549 by DNA alkylation. In the near future, graphene-based systems will establish potential nanosystems in cancer treatment due to the additive effect of graphene with various therapeutic agents.

3D Printed Personalized Medicine for Cancer: Applications for Betterment of Diagnosis, Prognosis and Treatment.

Cancer treatment is challenging due to the tumour heterogeneity that makes personalized medicine a suitable technique for providing better cancer treatment. Personalized medicine analyses patient-related factors like genetic make-up and lifestyle and designs treatments that offer the benefits of reduced side effects and efficient drug delivery. Personalized medicine aims to provide a holistic way for prevention, diagnosis and treatment. The customization desired in personalized medicine is produced accurately by 3D printing which is an established technique known for its precision. Different 3D printing techniques exhibit their capability in producing cancer-specific medications for breast, liver, thyroid and kidney tumours. Three-dimensional printing displays major influence on cancer modelling and studies using cancer models in treatment and diagnosis. Three-dimensional printed personalized tumour models like physical 3D models, bioprinted models and tumour-on-chip models demonstrate better in vitro and in vivo correlation in drug screening, cancer metastasis and prognosis studies. Three-dimensional printing helps in cancer modelling; moreover, it has also changed the facet of cancer treatment. Improved treatment via custom-made 3D printed devices, implants and dosage forms ensures the delivery of anticancer agents efficiently. This review covers recent applications of 3D printed personalized medicine in various cancer types and comments on the possible future directions like application of 4D printing and regularization of 3D printed personalized medicine in healthcare.

Strategies for the delivery of antidiabetic drugs via intranasal route.

Diabetes is a metabolic disorder defined by higher blood glucose levels in the body generally controlled by antidiabetic agents (oral) and insulin (subcutaneous). To avoid the limitations of the conventional routes such as lower bioavailability and pain at the site of injection in case of parenteral route modified delivery systems are proposed like transdermal, pulmonary and inhalation delivery and among the other delivery systems nasal drug delivery system that shows the advantages such as reduced frequency of dose, higher patient compliance, safety, ease of administration, prolonged residence time, improved absorption of drug in the body, higher bioavailability and stability. This review article discusses the strategies adopted for the delivery of antidiabetic drugs by the intranasal delivery system. The insulin and glucagon-like peptides on experimentation show results of improved therapeutic levels and patient compliance. The drugs are transported by the paracellular route and absorbed through the epithelial tight junctions successfully by utilising different strategies. The limitations of the nasal delivery such as irritation or burning on administration, degradation by the enzymes, mucociliary clearance, lesser volume of the nasal cavity and permeation through the nasal mucosa. To overcome the challenges different strategies for the nasal administration are studied such as polymers, particulate delivery systems, complexation with peptides and smart delivery using glucose-responsive systems. A vast scope of intranasal preparations exists for antidiabetic drugs in the future for the management of diabetes and more clinical studies are the requirement for the societal impact to battle against diabetes.

Quercetin-loaded platelets as a potential targeted therapy for glioblastoma multiforme cell line U373-MG.

Over the globe, the incidence of glioblastoma multiforme (GM) is very low, that is, 1-4 cases per 100,000, but it is fatal and cancer grows very fast inside the brain tissues, namely astrocytes and oligodendrocytes. Because of the rapid growth, it is difficult to halt the dissemination of tumor in adjacent tissues. Although temozolomide (TMZ) is a currently approved standard of care, it develops resistance over the period. Therefore, there is a need to develop a novel drug delivery system. In this work, authors have developed platelets as drug delivery carriers-loaded with quercetin (QCT) for targeting GM. The effect of QCT and QCT-platelet was assessed on the U373-MG cell line. Natural human platelets were used as carriers for drug loading and drug delivery. Platelets possess an open canalicular system that allows the uptake of drug molecules in the platelet cytoplasm. The study showed that the maximum encapsulation efficiency of QCT-platelet was 93.96 ± 0.12% and the maximum drug release in 24 h was 76.26 ± 0.13% in-vitro at pH 5.5 that mimics the tumor microenvironment. In this work, there is a three-fold enhancement of solubility of QCT. The cytotoxic activity of QCT-platelets was studied in the U373-MG human astrocytoma glioblastoma cell line and the cell viability was 14.52 ± 1.53% after 48 h. Thus, platelets were proved as good carriers for therapeutic moieties and can be effectively used to target the glioblastoma tumor in the near future.

Quality by Design Approach for Development and Optimization of Rifampicin Loaded Bovine Serum Albumin Nanoparticles and Characterization.

BACKGROUND: Rifampicin is one of the first-line drugs used for tuberculosis therapy. The therapy lasts for a long time. Thus, there is a need to develop a sustained release formulation of rifampicin for intravenous application. AIM: This study is focused on preparing rifampicin-loaded bovine serum albumin nanoparticles (RIF BSA NPs) suitable for intravenous application using systematic quality by design (QbD) approach. OBJECTIVES: The main objective of this study is optimizing particle size and entrapment efficiency of rifampicin-loaded bovine serum albumin nanoparticles (RIF BSA NPs) and making them suitable for intravenous application using QbD approach. METHODS: Quality target product profile was defined along with critical quality attributes (CQAs) for the formulation. 32 factorial design was used for achieving the predetermined values of CQAs, i.e., mean particle size <200 nm and percent entrapment efficiency>50%. Incubation time of drug with colloidal albumin solution and ratio of rifampicin to albumin, were selected as independent variables. Checkpoint analysis was performed to confirm the suitability of the regression model for optimization. RESULTS: The optimized RIF BSA NPs were characterized by FTIR, DSC, 1H NMR techniques. The NPs observed by transmission electron microscopy were spherical in shape. The rifampicin release could be sustained for 72 hours from BSA NPs matrix. RIF BSA NPs dispersion was stable at 5 ± 3°C for 72 hours. Non-toxicity of nanoparticles to RAW 264.7 cell line was proved by MTT assay. CONCLUSION: Development of RIF BSA NPs with desired quality attributes was possible by implementing the QbD approach. The optimized formulation suitable for intravenous application can potentially improve the therapeutic benefits of rifampicin.

Artificial intelligence (AI) impacting diagnosis of glaucoma and understanding the regulatory aspects of AI-based software as medical device.

Glaucoma, the group of eye diseases is characterized by increased intraocular pressure, optic neuropathy and visual field defect patterns. Early and correct diagnosis of glaucoma can prevent irreversible vision loss and glaucomatous structural damages to the eye. However, greater chances of misdiagnosis by the currently used conventional methods for diagnosis open up ways for more advanced techniques like the use of artificial intelligence (AI). Artificial intelligence coupled with optical coherence tomography imaging creates an algorithm that can be effectively used to make a model of complex data for detection as well as diagnosis of glaucoma. The present review is an attempt to provide state-of-the-art information on various AI techniques used in the diagnosis and assessment of glaucoma. The second part of the review is focused on understanding how the AI along with machine learning (ML) can be potentially used to be subjected for software as a medical device (SaMD) in precise diagnosis or early detection of disease conditions.

Strategic consideration for effective chemotherapeutic transportation via transpapillary route in breast cancer.

Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. The current treatment option for breast cancer includes drug treatment (Chemotherapy and hormone therapy) or surgery (mastectomy and lumpectomy). The major drawbacks of chemotherapy include rapid metabolism, limited ductal exposure, lower bioavailability, higher elimination rate, undesirable side effects, and high dose of drug. Localized application of drug to breast achieves higher drug levels at the tumor site and reduces systemic drug distribution. Permeation of drug by local application is mainly by transepidermal and transductal routes. The multiple duct openings of mammary papilla provide a higher permeable surface for transport of drug. Various formulation approaches like conjugated nanocarriers, microemulsion, nanoemulsion, liposomes, microneedles and iontophoresis are used to achieve a tailored and targeted drug delivery to underlying breast tissue. Localized transport of drug via transpapillary route has developed a novel and effective non-invasive drug delivery approach to achieve a systemic drug level at the tumor site in the management of breast cancer.

Phytoconstituents and pharmaco-therapeutic benefits of pitaya: A wonder fruit.

Dragon fruit has caught the attention of many researchers in the last few years because of its vast therapeutic potential. The fruit is enriched with several phytochemical constituents having tremendous pharmacological properties. It is traditionally used as a coloring agent. Some newly explored therapeutic applications include its use as an antioxidant, antimicrobial, antidiabetic, anticancer, and nutraceutical. The phytoconstituents can be extracted from flesh, peel, and seeds of the fruit. The fruit is known to be a rich source of betacyanin, vitamin C, and lycopene. The current review is focused on phytochemical constituents of dragon fruit along with its pharmacological activities. It also sheds light on the safety aspects of the fruit. The review will pave a path for researchers to study this marvel fruit further for societal benefit. Advanced research on dragon fruit will unleash many more therapeutic benefits and can give mechanistic insight about its activities. PRACTICAL APPLICATIONS: Phytoconstituents play a vital role in the treatment of various diseases and for the improvement of human health, in general. Dragon fruit is known to be having antioxidant, anti-microbial, anti-diabetic, anti-cancer applications. The fruit can also be used as a nutraceutical (functional food). To grab all the benefits from this fruit, its phytoconstituents and pharmaco-therapeutic aspect have to be thoroughly studied. This review can be very useful for researchers across different fields like botany, agriculture, pharmacy, etc., to bridge the gap for collaborative work on dragon fruit, which will help in finding solutions for many modern diseases.