Preclinical pharmacology and pharmacokinetics of curcumin tagged cilostazol nanodispersion for the management of diabetic nephropathy in wister rat model.

To evaluate the therapeutic potential of curcumin tagged cilostazol solid nano dispersion in wistar rat streptozotocin-nicotinamide-induced diabetic nephropathy. Cilostazol (CLT), a Phosphodiesterase (PDE) inhibitor has an inhibitory effect on reactive oxygen species (ROS), and Curcumin (Cur), an antioxidant, and anti-inflammatory, are water-soluble. Solid Nano dispersions were developed using the "Box-Behnken Design" and emulsion solvent evaporation procedure to improve the solubility and bioavailability. Streptozotocin (SPZ) and Nicotinamide (NA) caused diabetes in Wistar rats. DN developed 30-45 days after disease induction. All rat groups underwent histological, biochemical and pharmacokinetic evaluation. The optimized batch of Cilostazol Loaded Novel Curcumin Tagged Solid Nanodispersion (CLT-15 SND) estimated renal, lipid, and cytokine profiles better than the conventional batch. CLT-15 SND, given orally to diabetic rats for 45 days, significantly lowered fasting BGL and IL-6 levels and improved lipid and kidney-profile markers and body weight compared to plain Cilostazol Loaded Solid Nanodispersion (CLT-15 WC SND). CLT-15 SND treatment groups showed decreased blood glucose by 3.38 and 9.71 percent, increased body weight by 2.81 and 5.27 percent, improved Interleukin-6 (IL-6) by 21.36 and 18.36 percent, improved urine albumin levels by 5.67 and 14.19 percent and creatinine levels by 3.125 and 37.5 percent, improved serum urea by 30.48 percent, increased serum albumin by 2.59 and 11.18 percent, and decreased creatinine and 5.03 and 8.12 percent, respectively as compared to CLT-15 WC and MP treatment animal groups. CLT and Cur reduced IL-6, kidney, and lipid markers, demonstrating their renoprotective and pancreas-protective effects. CLT and Cur's inhibition may be the mechanism.

Human immunodeficiency virus infection challenges: Current therapeutic limitations and strategies for improved management through long-acting injectable formulation.

HIV infection has been a severe global health burden, with millions living with the virus and continuing new infections each year. Antiretroviral therapy can effectively suppress HIV replication but requires strict lifelong adherence to daily oral medication regimens, which presents a significant challenge. Long-acting formulations of antiretroviral drugs administered infrequently have emerged as a promising strategy to improve treatment outcomes and adherence to HIV therapy and prevention. Long-acting injectable (LAI) formulations are designed to gradually release drugs over extended periods of weeks or months following a single injection. Critical advantages of LAIs over conventional oral dosage forms include less frequent dosing requirements, enhanced patient privacy, reduced stigma associated with daily pill regimens, and optimised pharmacokinetic/pharmacodynamic profiles. Several LAI antiretroviral products have recently gained regulatory approval, such as the integrase strand transfer inhibitor cabotegravir for HIV preexposure prophylaxis and the Cabotegravir/Rilpivirine combination for HIV treatment. A leading approach for developing long-acting antiretroviral depots involves encapsulating drug compounds in polymeric microspheres composed of biocompatible, biodegradable materials like poly (lactic-co-glycolic acid). These injectable depot formulations enable high drug loading with customisable extended-release kinetics controlled by the polymeric matrix. Compared to daily oral therapies, LAI antiretroviral formulations leveraging biodegradable polymeric microspheres offer notable benefits, including prolonged therapeutic effects, reduced dosing frequency for improved adherence, and the potential to kerb the initial HIV transmission event. The present manuscript aims to review the pathogenesis of the virus and its progression and propose therapeutic targets and long-acting drug delivery strategies that hold substantial promise for enhancing outcomes in HIV treatment and prevention.

Topical delivery of insulin using novel organogel formulations: An approach for the management of diabetic wounds.

Diabetes mellitus is a growing chronic form of diabetes, with lengthy health implications. It is predicted as poor diabetic wound recovery affects roughly 25% of all diabetes mellitus patients, frequently resulting in lower traumatic injury and severe external factors and emotional expenses. The insulin-resistant condition increases biofilm development, making diabetic wounds harder to treat. Nowadays, medical treatment and management of diabetic wounds, which have a significant amputation rate, a high-frequency rate, and a high death rate, have become a global concern. Topical formulations have played a significant part in diabetic wound management and have been developed to achieve a number of features. Because of its significant biocompatibility, moisture retention, and therapeutic qualities, topical insulin has emerged as an appealing and feasible wound healing process effector. With a greater comprehension of the etiology of diabetic wounds, numerous functionalized topical insulins have been described and shown good outcomes in recent years, which has improved some diabetic injuries. The healing of wounds is a physiological phenomenon that restores skin integrity and heals damaged tissues. Insulin, a powerful wound-healing factor, is also used in several experimental and clinical studies accelerate healing of diverse injuries.

Technical Considerations, Applications, and Benefits of Organogels in Topical Drug Delivery Systems.

Organogels represent semi-solid systems where an organic liquid phase is entrapped within a three-dimensional network formed by self-assembled, crosslinked, or entangled gelator fibers. These versatile materials find applications in a wide range of fields, including chemistry, pharmaceuticals, cosmetics, biotechnology, and food technology. Notably, in pharmacology, they serve as valuable platforms for drug and vaccine delivery, facilitating the transport of active ingredients through various routes such as transdermal, oral, and parenteral. However, their previous utility as drug delivery systems was hindered by the toxicity associated with the organic solvents used. The pharmacokinetics of medications delivered via organogels are primarily influenced by the distinctive properties of these materials, specifically their "high permeability and poor aqueous solubility," which can impact the bioavailability of the drugs. Organogels can be employed topically or for the controlled release of medications through cutaneous administration and percutaneous absorption, expanding their scope of application beyond conventional drug delivery methods. Organogels hold significant promise as drug delivery vehicles due to their biocompatibility, non-irritating properties, and thermoremanent characteristics. They enable the formulation of diverse drug delivery systems by incorporating both hydrophilic and hydrophobic bioactive compounds within the gel matrix. This comprehensive review offers an overview of organogels, encompassing their nature, synthesis, characterization, and properties. Special attention is directed towards cutting-edge technologies employed in designing organogels as potential controlled delivery systems, with a focus on their emerging therapeutic applications.

Design, Development and In-Vitro Characterization of Insulin Loaded Topical Pluronic-Lecithin Based Organogel Formulation for the Management of Diabetic Wound.

AIM: To develop and characterize the topical insulin-loaded organogel formulation for the management of diabetic wounds. OBJECTIVES: To formulate and evaluate organogel of insulin that can serve as a topical administration for promoting enhanced wound healing in diabetic patients by providing sustained and localized delivery of drug to the wound site. METHODOLOGY: The insulin organogel formulated by the micro-emulsion method involves mixing the "aqueous and oil phases" at high shear. Physical and chemical properties, as well as an in vitro study with a Franz diffusion chamber, were used to evaluate the prepared organogel. RESULTS: All formulations proved to be off-white, homogeneous, washable, and had a pH between 6 and 6.5; moreover, they were non-irritating and skin-compatible. Formulations F1-F6 had viscosity ranging from 2058 to 3168 cps, spreadability ranges of 0.35 to 0.52 g*cm/s, and gel transition ranges of 28.33 to 35.33 °C. In formulations F1-F3, the concentration of lecithin was gradually increased, and in formulations F4-F6, the concentration of PF-127 was increased, resulting in a decrease in gel transition temperature, an increase in viscosity, and a gradual change in spreadability. The higher-viscosity formulations were much more stable and had better drug release. All formulations were fitted to a kinetic model belonging to first-order kinetics. However, after examining the parameter evaluation, it was found that the formulations F2 and F6 were better suited to the kinetic model and were consistent with the first-order and Higuchi models in Korsmeyer-Peppas F2 (r2 = 0.9544 and n = 1.0412); F6 (r2 = 0.9019 and n = 1.0822), which was a confirmation of the sustainability of the release system with matrix diffusion and drug delivery mechanisms that were based on the Super-Case II transport. CONCLUSION: Further research and clinical trials are needed to validate its efficacy, optimize the formulation, and establish its long-term safety. Topical insulin organogel has the potential to revolutionize diabetic wound management by improving healing outcomes, reducing complications, and raising the standard of living for those who have diabetes.

Diabetic Wound: Pathophysiology, Complications and Treatment Strategies.

Diabetic wound healing is expected to affect 25% of all diabetics, resulting in less severe external factors, economic costs, and less trauma. Topical formulations have been continually improved to achieve a range of amazing properties and have had a significant impact on the management of diabetic wounds. Topical insulin has become one of the most attractive and convenient wound healing techniques due to its excellent biocompatibility, water retention, and therapeutic properties. Multiple versatile topical insulins have been identified and have shown promise over the past few years as they greatly facilitate the management of diabetic wounds as we understand their etiology. The physiological wound healing process repairs damaged tissue and restores skin integrity. For about a century, insulin, a powerful healing agent, and it has been utilized in several clinical and experimental researches research studies to accelerate the healing of various injuries.

Dual-targeted transferrin and AS1411 aptamer conjugated micelles for improved therapeutic efficacy and imaging of brain cancer.

Brain tumors represent an aggressive form of cancer, posing significant challenges in achieving complete remission. Development of advanced therapies is crucial for improving clinical outcomes in cancer patients. This study aimed to create a novel treatment approach using dual-targeted transferrin (TF) and AS1411 conjugated micelles, designed to enhance therapeutic effectiveness of docetaxel (DTX) and facilitate gadolinium (Gd) based imaging in brain cancer. Micelles were prepared using a slightly modified solvent-casting method, and the dual-targeting ligands were attached to the micelle's surface through a physical adsorption process. Average particle size of micelles ranged from 117.49 ± 3.90-170.38 ± 3.39 nm, with a low polydispersity index. Zeta potential ranged from - 1.5 ± 0.02 to - 18.7 ± 0.04 mV. Encapsulation efficiency of DTX in micelles varied from 92.64 ± 4.22-79.77 ± 4.13 %. Simultaneously, encapsulation of Gd in micelles was found to be 48.27 ± 3.18-58.52 ± 3.17, respectively. In-vitro drug release studies showed a biphasic sustained release profile, with DTX and Gd release continuing up to 72 h with their t50 % at 4.95, 11.29, and 24.14 h for GDTP, GDTP-TF and GDTP-TF-AS1411 micelles, respectively. Cytotoxicity effect of GDTP-TF-AS1411 micelles has shown significant improvement (P < 0.001) and reduced IC50 value up to 0.19 ± 0.14 µg/ml compared to Taxotere® (2.73 ± 0.73 µg/ml). Theranostic study revealed higher accumulation of GDTP-TF and GDTP-TF-AS1411 micelles free GD treated animal brains. The AUC of GDTP-TF-AS1411 micelles exhibited 23.79 ± 17.82 µg.h/ml higher than Taxotere® (14.14 ± 10.59 µg.h/ml). These findings direct enhanced effectiveness in brain cancer therapy leading to improved therapeutics in brain cancer patients. The combined targeted ligands and therapeutic agents strategy can direct advancement in brain cancer therapy and offer improved therapy for patients.

Nano Architect-Based Targeted Delivery Systems for Diabetic Nephropathy: A Review.

Diabetes mellitus is a long-lasting disease that is very common in the age group above 20 years and is characterized by hyperglycemia with other complications like Diabetic Nephropathy (DN). The management of DN focuses on mainly four regions: reduction of cardiovascular risks, control of blood glycemic levels, control of the blood pressure (BP) profile, and the use of therenin-angiotensin system (RAS). Although BP management and RAS-acting agents can postpone the onset of DN, they cannot prevent it. In the modern era, nanotechnological interventions have spread rapidly in the field of medicine. Patient defiance is considered important in diabetes management when long-term or continuous management is required. Nano pharmaceuticals have been shown to increase compliance of diabetic patients by providing multiple ways of drug delivery, controlling release profile, increasing biological steadiness, targeting efficacy, and decreasing toxic profile. Nanoscale formulations of botanical antidiabetic molecules improve clinical efficacy and treatment compliance by overcoming associated biopharmaceutical and pharmacokinetic barriers. Therefore, the development of nanopharmaceuticals can be considered to be a possible answer to attain the finest scientific effect of the plant-based anti-diabetic molecule. Nevertheless, further studies are needed to create clinical research-based and therapeutically effective nanoforms of antidiabetic plant-based molecules to combat the most dreaded disease of diabetes and its known present complications.

In vitro characterization of tofacitinib loaded novel nanoemulgel for topical delivery for the management of rheumatic arthritis.

The purpose of the current study is to prepare the tofacitinib (TFB) nanoemulgel (NEG) for topical administration with optimized particle size, high loading efficiency, and better penetration through the skin for the treatment of rheumatic arthritis. The topical delivery of this drug avoids the hazards associated with oral delivery like upper respiratory tract infections and neutropenia. The formulations were prepared using the high-energy ultrasonication method. Oleic acid, tween 80, and propylene glycol were used to prepare TFB nanoemulsion (NE) which is then homogenized with carbopol-934 hydrogel to get the NEG loaded with TFB. The concentration of independent variables such as X1 (oil phase), X2 (surfactant), and X3 (cosurfactant) was optimized using the Box-Behnken design to check its impact on dependent variables such as Y1 (particle size) and Y2 (loading efficiency) of the NE. The minimum particle size of 106.3 ± 2.8 nm and maximum loading efficiency of 19.3 ± 1.8% were obtained for NE. The NEGs were evaluated for different organoleptic and physicochemical stability which were found within the normal range. The in vitro release studies showed 89.64 ± 0.97% cumulative release of TFB from NEG over the period of 24 h. The drug release data were fitted in different kinetic models and it followed Higuchi and Korsmeyer-Peppas model clearly showing the non-Fickian drug release from matrix system. As a result, the TFB NEG that have been produced could be a viable delivery mechanism for topical route.

Innovation in cancer therapeutics and regulatory perspectives.

Cancer therapy has undergone a drastic revolution in the past few decades with the introduction of several novel therapies, like immunotherapy (active and passive), stem cell-based therapies, and nanocarrier-based therapies. These therapies have addressed the issues of conventional cancer therapy (chemotherapy or radiotherapy), like specificity and off-target effects. Further, the introduction of such treatments has improved survival and converted a terminal disease into a more manageable condition. However, many clinical, ethical, and regulatory issues are raised with such novel additions. Several effective therapies are under research but could not come to market or are delayed due to regulatory concerns for marketing approval. The scope of this review encompasses the examination of these regulatory issues and discuss their possible solutions. A practical and flexible regulatory approach, harmonized globally, could help the patients suffering from a terminal illness to lead a quality life.

Utilization of kinase inhibitors as novel therapeutic drug targets: A review.

Kinase inhibitors are a significant and continuously developing division of target therapeutics. The drug discovery and improvement efforts have examined numerous attempts to target the signaling pathway of kinases. The Kinase inhibitors have been heralded as a game-changer in cancer treatment. For developing kinase inhibitors as a treatment for various non-malignant disorders like auto-immune diseases, is currently undergoing extensive research. It may be beneficial to investigate whether cell-specific kinase inhibitor administration enhances therapeutic efficacy and decreases adverse effects. The goal of the current review is to gain insight into the role of kinase inhibitors in facilitating effective target drug delivery for the treatment of various anti-inflammatory, auto-immune, and anticancer disorders. The aim of this review is also to shed light on drug discovery approaches for kinase inhibitors, their mode of action, and delivery approaches. The variation in the binding of kinases bestows different target approaches in drug design, which can be employed for designing the targeted molecules. Several target sites have been studied, exceeding the design of drugs for various diseases like cancer, Alzheimer's, rheumatoid arthritis, etc. Diverse delivery approaches have also been studied for the targeted application of kinase inhibitors.

An insight of nanogels as novel drug delivery system with potential hybrid nanogel applications.

Nanogels are cross-linked, nano-sized hydrogels with dimensions ranging from 20 to 200 nm. Nanogel-based nanoplatforms have proven to be an excellent choice for pharmaceutical formulations. Nanosystems have properties that are very useful in polymeric drug delivery applications, and their particular strength is that they have these nanosystemic properties and can thus merge with polymeric materials. Drug-carrier size is designed to be nano-sized in order to maintain optimal stability, resulting in more surface area and interior space. This also allows for a prolonged period of time for loaded pharmaceuticals to circulate. They can be classified by stimuli responsive or non-responsive behavior and type of linkages present in the network chains of gel structure. Nanogel can be synthesized by Photolithographic, modified pullulan, emulsion polymerization reverse microemulsion polymerization inverse miniemulsion polymerization and free radical crosslinking polymerization technique. Hybrid nanogels are different from conventional polymer nanoparticles often employed for drug administration. They can encapsulate bioactive medicines and regulate the release of such medications over time and in particular areas. The hybrid nanogels used to create a specific form of the hybrid, especially one geared towards increasing targeted drug delivery, enhance the effectiveness of ailment treatments, but perhaps the introduction of a multifunctional nanogel-based drug delivery system.

Design expert assisted formulation, characterization and optimization of microemulsion based solid lipid nanoparticles of repaglinide.

Repaglinide, a member of the meglitinide class of drugs, is a new anti-diabetic agent that is utilized as an oral hypoglycemic agent. Using glyceryl monostearate, cetyl palmitate, and tristearin as lipids and poloxamer 188 as a surfactant, repaglinide-loaded solid lipid nanoparticles were created. Solid lipid nanoparticles were prepared utilizing an o/w microemulsion technique, which included the lipids glyceryl monostearate and tristearin, as well as waxes such as cetyl palmitate and the surfactant poloxamer 188. The mean particle size of the solid lipid nanoparticles formed was around 339 nm, with an entrapment efficiency of 82.20%. In-vitro release studies continued to be conducted using the dialysis bag diffusion technique. Within 12 h, the cumulative drug release was 88.4%. The results indicate that repaglinide was released more slowly from solid lipid nanoparticles made from tristearin and glyceryl monostearate in an equal ratio. Tristearin found the controlled release and extreme entrapment from other lipid carriers like glyceryl monostearate and cetyl palmitate. Differential scanning calorimetry demonstrates that repaglinide is entangled in amorphous or molecular state within solid lipid nanoparticles. SEM microscopy revealed that the produced repaglinide solid lipid nanoparticles had a spherical shape. After one month of storage at 2-8 °C, short-term stability testing revealed no significant alteration.

Formulation and evaluation of thermosensitive flurbiprofen in situ nano gel for the ocular delivery.

The contemporary research implicates the formulation and evaluation of a thermosensitive in situ nano gelling method to improve solubility and ocular residence time of flurbiprofen. This study was carried out in two phases. In the first phase, an insolubility drug has been formulated in the form of a nanoparticulate system and evaluated for its characteristics. The nanoparticles obtained demonstrated an average size array of 150 to 250 nm in diameter, up to 79.35% encapsulation efficiency, and up to 93.42% drug release throughout 2 h. In the second phase, nanoparticulate systems were dispersed in aqueous solutions of Pluronic F 127 (14%) and various concentrations of Carbopol 934 in combination to form an in situ nano gel. The prepared in situ gel was investigated for its physicochemical properties like pH, flowability, sol-gel transition temperature, gelling capacity, and rheological properties. Carbopol 934 did not significantly affect sol-gel transition temperature in optimized concentration (<0.3%) but altered gelling capacity, pH, and transparency of the formulations. In vivo resident time and eye irritation test was evaluated in the rabbit eye. In optimized in situ gelling formulation (NIGF3), approximately 95% of in vitro drug release was observed after 6 h. NIGF3 increased precorneal residence time and high concentration in aqueous humor when paralleled to flurbiprofen eye drops. Greater concentration of drug in aqueous humor was due to its improved saturation solubility of the drug, and amplified residence time was attributed to the formation of gel matrix-embedded nanoparticles. This demonstrated that in situ nano gels (NIGF3) comprehending aqueous solutions of 0.3% w/v concentrations of Carbopol 934 with Pluronic F 127 may ominously persist the residence time and mend bioavailability of a water-insoluble drug.

3D Printing Technology in Pharmaceutical Dosage Forms: Advantages and Challenges.

Three Dimensional (3D) printing is a promising method for quick prototyping and manufacturing of any material. It is similar to photocopy or printing, where the new materials are formed on layers (3D) like their mother component. Following its growth and advancement in the 1980s, its application in pharmaceuticals is still limited. It has become one of the most innovative and influential tools serving as a technology for developing dosage forms from the last decade. The potential of 3D printing to produce drugs for precise measurement customized to specific patients' needs has shown the possibility of developing personalized medicines to novel dosage forms. The breakthrough allows the clear perception of the dosage structures on different shapes, sizes, surfaces and the associated challenges in delivering them by using such designed conditions. There are different difficulties related to the correct utilization of 3D imprinting in the pharmaceuticals, which have a strong impact on the scope of this technology. Recent advancements in the field of 3D printing technology used in the pharmaceutical industry mainly focused on different techniques for the fabrication of different dosage forms. The Food and Drug Administration's (FDA) recent approval of the first 3D prescription highlights possibilities for 3D printing innovation in the field of pharmaceutical drug supply. This analysis assesses 3D printing advancement possibilities, particularly in the area of custom prescriptions. This technology can be regarded as the future produced on demand, low-cost solid dosage forms and helps minimize side effects due to overdose.

Formulation and evaluation of gastro-retentive floating bilayer tablet for the treatment of hypertension.

The paper aimed to progress an ideal gastro retentive drug delivery system intended for directing Losartan and Hydrochlorothiazide as a fixed-dose combination for anti-hypertensive therapy. The bilayer tablets were primed through direct compression method. Losartan was formulated by means of a floating layer expending hydrophilic swellable polymer Hydroxy Propyl Methyl Cellulose K4M, ethyl cellulose (4cps) as a buoyancy enhancer, sodium bicarbonate as a gas spawning agent. The amount of polymer blends remains optimized using 23 full factorial designs. The clout of experimental factors such as swelling agent concentration, buoyancy enhancer and gas generating agent on floating lag time, total floating time, T50% and % drug release remain investigated to get optimized formulation. The responses remain analyzed using Analysis of variance, and polynomial equation stood created for every retort using Multiple linear regression analysis. Entirely preparations floated for more than 12 h. The release pattern of losartan stood fitted to diverse models based on the coefficient of correlation (r). All the formulations, except F2, showed the Korsemeyer-Peppas model as the best fit model. Formulation F2 showed the zero-order model. Diffusion exponents (n) remained indomitable designed for entirely formulations (0.45-0.89), accordingly the chief drug discharge mechanism was non-fickian (anamolous) transport. Formulation F4 containing 20% w/w Hydroxy Propyl Methyl Cellulose K4M, 15% Sodium bicarbonate and 5% ethyl cellulose (4cps) was the best formulation as per the range of drug release remain institute to be more than 95 % in 12h and floating lag time was 20.15 s. The immediate-release layer stood optimized using crospovidone and Indion 414 as a super disintegrant. Formulation A8 containing 2% Indion 414 was considered as optimized formulation as it released 99% drug within 35 min and possessed less disintegration time. Optimized formulation F4 from the controlled-release layer and A8 from immediate-release layer was used to formulate bilayer tablet. The optimized formulation was imperilled to stability reading for three months at 40○C/75% relative humidity. The stability revision exhibited no substantial alteration in the appearance of tablets, floating characteristics, drug content and in-vitro drug dissolution. Consequently, a biphasic drug release design was effectively accomplished over the formulation of floating bilayer tablets.

Unwinding Complexities of Diabetic Alzheimer by Potent Novel Molecules.

Diabetes mellitus is one of the aggressive disorders in global society. No pharmacotherapy is available for permanent diabetes cure, although management is possible with drugs and physical activities. One of the recent complications noticed in type 2 diabetes mellitus includes diabetes-induced Alzheimer. It has been proposed that the possible diabetes-induced Alzheimer could be of type 3 diabetes. A variety of cross-sectional studies have proved that type 2 diabetes mellitus is one of the factors responsible for the pathophysiology of Alzheimer. New drug molecules developed by pharmaceutical companies with adequate neuroprotective effect have demonstrated their efficacy in treatment of Alzheimer in various preclinical diabetic studies. Patients of type 2 diabetes mellitus may show the benefit with existing drugs but may not cause complete cure. Extensive studies are being carried out to find new drug molecules that show their potential as antidiabetic drug and could treat type 2 diabetes-induced Alzheimer as well. This review provides an overview about the recent advancement in pharmacotherapy of diabetes-induced Alzheimer. The pathomechanistic links between diabetes and Alzheimer as well as neurochemical changes in diabetes-induced Alzheimer are also briefed.

Integration of pharmacogenomics and theranostics with nanotechnology as quality by design (QbD) approach for formulation development of novel dosage forms for effective drug therapy.

To cater to medication needs in the future healthcare system, we need to shift from the conventional system of drug delivery to modern molecular signature-based drug delivery systems. The current drug therapies are either less effective, ineffective, or produce numerous adverse reactions. One scientific principle or discipline cannot adequately address all the problems, so we need an innovative application of the current scientific principles. Here we are proposing a novel concept of nanoformulation based on pharmacogenomics and theranostics for personalized error-free and targeted therapeutic agent delivery. The addition of more knowledge about the human genome opens the new way to study disease-gene, gene-drug, and drug-effect interactions, which is the basis of future medicines. Pharmacogenomics provides information about the disease etiology, role in genes in disease pathophysiology, disease biomarkers, drug targets, drug effects, and the fate of drugs inside the body. Theranostics approach utilizes the above information in diagnosis, treatment, and monitoring of the disease on a real-time basis. Personalized dosage forms can be formulated into a nanoformulation that provides a better therapeutic effect and minimizes adverse drug reactions. The therapeutic system needs to be shifted from the principle of one drug fits all to one drug unique population. In the present manuscript, we tried to conceptualize a modern therapeutic system by combining the three approaches viz. pharmacogenomics, theranostics, and nanotechnology applied in the area of formulation development to produce a multifunctional single tiny entity.

Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism Is Not Responsible for Antihypertensive Therapy Induced New Onset of Type 2 Diabetes in Essential Hypertension.

BACKGROUND: Antihypertensive drug therapies have been reported to be associated with new onset of type 2 diabetes mellitus in some hypertensive patients after prolonged use. Angiotensin converting enzyme (ACE) gene has been found to affect essential hypertension, response of antihypertensive therapies, and glycemic disturbances. Therefore, ACE gene I/D polymorphism may be associated with risk of new onset of type 2 diabetes via metabolic disturbances, glycemic dysregulation, and insulin resistance. AIM: To assess the correlation between ACE gene I/D polymorphism and glycemic disturbance under influence of diuretic and other antihypertensive drug therapies. MATERIALS AND METHODS: We recruited 270 normotensive patients as control (150 men and 120 women), 270 hypertensive patients (95 men and 175 women), and 240 hypertensive with new onset of diabetes patients (80 men and 160 women). All samples were genotyped for ACE gene polymorphic alleles and relationship between different genotypes and anthropometric and clinical parameters along with drug therapies was established and analyzed. RESULTS: Baseline clinical (systolic blood pressure, diastolic blood pressure, and fasting blood glucose level) and anthropometric parameters (height, weight, waist circumference, hip circumference, waist-hip ratio, and body mass index) of study populations were found highly statistically significant (P < .05) when compared among study groups. Furthermore, genotype wise comparison of all these parameters in essential hypertensive (EH) and essential hypertensive with onset of diabetes (EHNOD) patients found most of them nonsignificant and no variation was found with respect to different genotypes of ACE gene. The genotype wise comparison of clinical parameters among different antihypertensive drug therapy was found statistically nonsignificant in both EH and EHNOD patients. DISCUSSION: Anthropometric parameters can be taken as the risk indicator factors for hypertension and diabetes. However, ACE gene polymorphism may not be a risk factor for development of diabetes in hypertensive patients. CONCLUSION: The present study suggested that ACE gene polymorphism did not show any significant association with the risk of new onset of diabetes in EH patients and more detailed studies with large population size are needed.

Alpha Adducin (ADD1) Gene Polymorphism and New Onset of Diabetes Under the Influence of Selective Antihypertensive Therapy in Essential Hypertension.

BACKGROUND: Different antihypertensive therapies (especially diuretics) are reported to induce the new onset of diabetes in some hypertensive patients. α-adducin-1 (ADD1) gene is salt sensitive gene which has its role in etiology of hypertension via salt sensitivity. Therefore, the G460T polymorphism of ADD1 gene may be associated with new onset of diabetes under the influence of diuretic and other antihypertensive therapies. AIM: To assess the correlation between genetic polymorphism (ADD1 G460T polymorphism) and glycaemic disturbance under influence of diuretic and other antihypertensive drug therapies. MATERIALS AND METHODS: We recruited study subjects, 270 normotensive as control (150 male and 120 females), 270 hypertensive patients (95 male and 175 females) and 240 hypertensive with new onset of diabetes patients (80 male and 160 females). All study samples were genotyped for ADD1 polymorphic alleles and analyzed the relationship between different genotypes with respect to anthropometric and clinical parameters along with drug therapies. RESULTS: Clinical and anthropometric parameters (such as age, SBP, DBP, FBG, height, weight, WC, HP, W/H ratio, and BMI) of study population were found highly statistically significant (p<0.05) at base value. Further, genotype wise comparison of all the above parameters revealed most of them as non-significant (p>0.05). Whereas, comparison between genotype and different antihypertensive drug therapy of hypertensive patients, specifically, diuretic therapy as mono in male (p=0.0227) and female (p=0.0292) and in combination with BBs in both male (p=0.0023) and female (p=0.0079) revealed a higher FBG level in variant T allele. In case of hypertensive with new onset of diabetes patients, only female population showed a slightly statistically significant (p=0.0413) difference in FBG level with diuretic mono therapy. Other antihypertensive drug therapies were safe and effective either as mono or in combination therapy. DISCUSSION: Anthropometric parameters may be the indicative factors for hypertension and diabetes. Variant T allele of ADD1 gene may be considered as the risk factor for the development of diabetes in hypertensive patients. Diuretics as mono therapy and in combination with BBs may be considered as the risk factor for new onset of diabetes in EH patients carrying variant T allele (either as TG or TT).