Wound healing is a complex biological event essential for tissue repair and regeneration. Despite their efficacy, conventional methodologies frequently encounter constraints such as the risk of infection and extended duration of healing. Recent developments have demonstrated the effectiveness of phytoconstituents in the treatment of wound healing because of their anti-inflammatory, antibacterial, and antioxidant properties. However, obstacles such as inadequate bioavailability and stability remain significant concerns. Hence, nanocarriers are considered as a revolutionary paradigm for these phytoconstituents. Nanocarriers possesses the potential to deliver plant bioactive to attain effective amount within therapeutic window for prolong duration. In last decades, researchers and scientists have explored the different nanocarriers like solid lipid nanoparticles, liposomes, nanofibers etc. for efficient delivery of plant bioactive. Nanocarriers have been mainly utilized to entrap the plant bioactive to increase their solubility, penetrability, half life (elimination), bioavailability, pharmacokinetics and therapeutics potential. Moreover, problems associated with nanocarriers such as nanotoxicity, scalability, regulatory aspects and translational gaps are considered as major concern to be overcome for its use. This review delves into the underlying mechanisms of wound healing, the therapeutic functions of various phytoconstituents, and the state-of-the-art nanotechnology-driven strategies that optimize their administration. Furthermore, it addresses clinical trials, regulatory frameworks, and safety considerations associated with nanocarriers in wound management. Thus, recent advances in the nanocarriers systems serve as promising approach for developing efficacious, sustainable, and individualized wound healing interventions.
This study aimed to create innovative transfersomes (TRFs) consisting of a lipid blend and a chemical permeation enhancer for efficient transdermal delivery of leflunomide (LFN). Leflunomide, a dihydroorotate dehydrogenase inhibitor, is mainly used to manage rheumatoid arthritis (RA). Oral consumption of LFN for RA can lead to adverse systemic effects; hence, local application is advisable. To develop topical dosage form of LFN, transfersomes with improved skin permeation capabilities were fabricated. The vesicle diameter of LFN-TRF was determined to be 181.2 ± 2.17 nm, zeta potential of − 29.2 ± 0.06 mV, PDI of 0.259 ± 0.006, and encapsulation percentage (EE) of 86.5 ± 3.45
>Luteolin, a naturally occurring flavonoid, exhibits potent anticancer activity but is limited by poor aqueous solubility and low oral bioavailability. This study aimed to develop and optimize a niosomal drug delivery system to enhance the solubility, stability, and therapeutic efficacy of luteolin against breast cancer. Luteolin-loaded niosomes were prepared using the ethanol injection method and lyophilized with 2.5
This study aims to formulate Clofazimine (CLOF)-loaded nanostructured lipid carriers (NLCs) for transdermal application, thereby improving the overall efficacy of the drug. NLCs loaded with clofazimine were developed using biocompatible lipids, characterised w.r.t. particle size, PDI and % entrapment efficiency and optimised using 'Box-Behnken design'. The optimum formulation was assessed for in vitro drug release, dermatokinetics & in vivo biocompatibility study. The characterisation of NLCs formulation revealed their globular shape with a particle size of around 192 nm, zeta potential of approximately of -30 mV and % EE of around 88.45%. Drug release demonstrated biphasic drug release from NLCs and follows the Higuchi release kinetics with a non-fickian release mechanism. The ex vivo study confirmed a 3.5 folds increase in permeation as compared with conventional gel formulation. Thus, the NLC based formulation exhibited around 350% increase in permeation as compared to plain gel of drug. The developed formulation was found to be biocompatible and exhibited no signs of irritancy or toxicity, according to the skin irritation study. Furthermore, formulation has good physicochemical stability with a shelf life of about 27 months. In conclusion the study suggests that NLC-loaded CLOF was applied topically to treat leprosy, providing improved skin penetration and effectiveness.
The study report development of a solid self-microemulsifying drug delivery system (S-SMEDDS) for Fimasartan (FMS), an antihypertensive agent with poor water solubility. Excipients were screened to formulate an optimized liquid SMEDDS (L-SMEDDS) containing Capmul MCM (30 %), Tween 80 (46.67 %), and Transcutol HP (23.33 %) co-surfactant, which exhibited strong thermodynamic stability. The L-SMEDDS was transformed into S-SMEDDS through adsorption utilizing Aerosil 200 and Neusilin US2. The SeDeM-Solid-Liquid Adsorption (SeDeM-SLA) model was applied to evaluate and select carriers based on their flow and compressibility properties, enabling efficient solidification without compromising performance. The selected Neusilin US2-based S-SMEDDS was characterized by FTIR, PXRD, DSC, and SEM. It showed enhanced dissolution (96 % in 60 min), maintained stability over 6 months, and demonstrated improved permeability over the pure drug. A pharmacokinetic study revealed a 2.86-fold increment in bioavailability than FMS (pure). The novelty of this work lies in the first-time integration of the SeDeM-SLA model for rational carrier selection and optimization of solid SMEDDS, providing an efficient and predictive method to augment formulation flowability and performance. In conclusion, S-SMEDDS effectively enhanced the oral delivery of FMS, and the application of the SeDeM-SLA model proved crucial in guiding the selection of suitable carriers and ensuring robust formulation performance.
The present study aims to formulate and optimized mucoadhesive chitosan-coated alginate microbeads as a guardian; encapsulating amoxicillin trihydrate for site specific H. pylori healing in peptic ulcer therapy. This study investigates a gastroretentive mucoadhesive drug delivery method for eliminating H. pylori at specific sites. Using ionotropic gelation, chitosan-coated alginate beads loaded with amoxicillin were formulated and optimized using Box Behnken design, considering concentration of polymer, drug and coating solution as a formulation variable. The optimized bead formulation exhibited in vitro drug release up to 8 h, following Korsmeyer-Peppas model. Release mechanism follows non-fictional anomalous transport, 86.54
Hydroxychloroquine (HCQ) has been used conventionally for the management of RA. However, due to its high dose and adverse effects associated with the long-term use, its therapeutic utility is often limited. This research was undertaken to develop an ethosomes based topical dosage form of HCQ, to improve the transdermal delivery of HCQ in patients with RA. Ethosomes were developed by varying the concentration of ethanol, phospholipids and surfactants in the formulations. The developed ethosomal formulation was characterized for particle size, zeta potential, PDI,
BACKGROUND:Tamoxifen citrate (TMC), an antiestrogenic drug, is employed in the healing of advanced breast cancer. However, its oral and parenteral route-associated side effects and solubility issues restricted its medical utilizations. OBJECTIVE:The research aimed to prepare a tamoxifen citrate-loaded transethosomal gel (TMC TEsG) to enhance TMC entrapment efficiency, in vitro dissolution, and ex vivo permeation. METHODS:TMC TEs were developed employing an HPH method and optimized using 23 factorial designs. The optimized TMC TEs were converted into TMC TEsG by cold dispersion. TMC TEs and TMC TEsG were estimated for particle size, microscopic, functional group interaction, crystalline, in vitro dissolution, ex vivo permeation, spreadability, TMC content, and texture analysis. RESULTS:The optimization study revealed the suitability and validity of 23 designs for developing TMC TEs. TMC TEs with particle size ~163.1 nm and zeta potential of ~-26.8 mV improved the physical stability and skin permeation. TMC TEs showed a high entrapment efficiency of ~84.49%. TEM depicts spherical and sealed structure vesicles of TMC TEs. Physical analysis supported the formation of TMC TEs. Vesicles improved the dissolution (~96%) compared to pure TMC (~68%). The TMC TEsG increased the permeation (~82%) compared to TMC gel (~55%). TMC TEsG with pH (~5.61), viscosity (~4077.5 cps), and spreadability (~49.84 g.cm/s) exhibiting safety and easy applicability to the skin. CONCLUSION:Outcomes suggest the transdermal permeation potential of design-generated flexible TMC TEs and, thus, could be employed to treat skin-related diseases.
Psoriasis is a chronic autoimmune skin disease, which affects the quality of life of patients. Cyclosporine (Cys-A) & Vitamin D (Vit D3) are crucial drugs used in the treatment of the disease. They are mainly administered via oral dosage forms for the treatment of psoriasis. However, their conventional dosage forms suffer from low oral bioavailability, along with systemic adverse effects. Developing the topical dosage forms of these drugs can be advantageous to overcome the problems associated with conventional therapy. Hence, ethosomes (ETH) were developed for the simultaneous administration of both the drugs. The particle size of the developed ethosomes was found to be 120.8 ± 5.6 nm, zeta potential value was found to be -24.7 ± 1.5 and entrapment efficiency was found to be 74.8 ± 1.52% & 80 ± 1.8% respectively, for Cys-A and Vit D3. In vitro drug release studies exhibited drug release of about 74% and 78% for Cys-A & Vit D3, respectively. Skin permeation studies demonstrated significantly higher drug permeation of ETH gel for Cys-A & Vit-D3 (71.6% and 72.2% respectively) than the conventional gel formulation (52.9% and 54.8% respectively). A cytotoxicity study conducted on the HaCaT cell line showed no cytotoxicity with ≥ 90% of cell viability. The therapeutic efficacy of the formulation tested on the in-vivo antipsoriatic rat model demonstrated comparable efficacy to that of the marketed formulation and the signs of inflammation were reverted within 14 days.
Microbial ocular infections, namely bacterial conjunctivitis (BC), are a major concern in the biomedical field. Nisin (NIS) is an amphiphilic natural antimicrobial peptide. It showed antibacterial potential against Pseudomonas aeruginosa, which is responsible for BC. Despite this, the application of NIS in pharmaceuticals for the treatment of ocular infections is hindered by several limitations that include poor aqueous solubility and stability. The preference for solid lipid nanoparticles (SLN) shows the aptitude to enhance solubility, bioavailability, etc., of therapeutically active molecules. Therefore, the present research work intends to prepare a thermoresponsive poloxamer 407 (P-407)-based in situ ocular gel of NIS-incorporated SLN using Box Behnken Design (BBD) for improved antibacterial application. Herein, NIS-SLN was formulated with glyceryl monostearate (GMS) and Tween 80 using a HSH-probe sonication method. It resulted in the spherical shape NIS-SLN with the particle size (PS) of 158.8 ± 13.56 nm, zeta potential (ZP) of -22.48 ± 1.86 mV, and drug loading (DL) of 12.8% ± 2.84%. The formulated thermo-responsive in situ gel (ISG) pH, gelling temperature, and viscosity were found to be 7.45 ± 0.02, 36.5°C ± 0.5°C, and 465.5 ± 6.5 cps, respectively, with drug release of 68.65% ± 5.1% over 24 h. Moreover, it shows improved permeation of 66.43% ± 2.6%, which might be because of the nanoscale dimensions of SLN and Tween 80. The formulation demonstrates good stability for 3 months and improved antimicrobial potential against P. aeruginosa compared to pure NIS, possibly owing to sustained release and improved penetration of NIS. Moreover, in vivo experiments demonstrated no irritation of the gel formulation, confirming biocompatibility with the ocular region. In conclusion, the SLN incorporated thermo-responsive P-407-based in situ ocular gel provides the improved potential of NIS. In the future, it will reveal a new horizon for the delivery of NIS and other molecules for ocular disease treatment.
Cotton stalk waste from agriculture has been shown to be a rich source of cellulose and lignin. In our study, we have developed the lignin-based hydrogel for the treatment of diabetic retinopathy (DR). Lignin's natural antioxidant and anti-inflammatory properties complement its function as a drug carrier, especially in conditions where oxidative stress and inflammation play a significant role, as in DR. The developed bioinspired hydrogel acts as a drug delivery vehicle for natural polyphenolic antioxidants like curcumin, naringenin and alpha-lactalbumin, which have beneficial therapeutic effects in DR due to their diverse therapeutic action. By taking complementary advantages of lignin, the therapeutic application of the developed lignin-based hydrogel with actives was studied in the treatment of DR, and in vitro characterization was performed with DLS, XRD, DSC,1HNMR, ATR-IR, and SEM analysis. The particle size of extracted lignin was found to be 282.8 nm by the DLS method, which is suitable for ocular delivery. ATR-IR analysis confirms the lignin functional groups. XRD revealed the amorphous nature of hydrogels. DSC revealed that lignin-based hydrogel was able to protect active molecules from thermal degradation. In vivo results confirmed the suppressed VEGF level in the vitreous fluid after 4 weeks of treatment. The proposed therapeutic lignin-based hydrogel possesses dose-dependent activity, which overcomes the major limitations of current treatment in DR, and advantages like self-administration, pocket friendly, non-invasive and painless treatment.
Stiripentol (STP), an antiepileptic drug, is administered orally in the form of capsule and dry suspension. However, it is extremely unstable in acidic environment. Hence, to find the feasibility of alternate route of administration and to enhance the bioavailability of drug, STP loaded intranasal in-situ nanolipoidal gel formulation was formulated. The nanostructured lipid carriers (NLC) of the drug were systematically optimized using QbD tool. Melt emulsification homogenization method was adopted to avoid the degradation of drug. The developed formulation was characterized w.r.t particle size, Polydispersity index (PDI), zeta potential (ZP) along with entrapment efficiency. The developed STP-NLC formulation was further loaded into thermosensitive polymeric solution to form in-situ STP-NLC-gel formulation and evaluated for the in vitro drug release, ex vivo permeation, pharmacokinetic behavior and pharmacodynamic efficacy. The developed formulation was found to possess a particle size of around 196 nm, PDI around 0.174 and entrapment efficiency of around 86
Angiotensin II receptor antagonist losartan potassium (LP) is a medication that can be consumed orally and is used to treat hypertension. LP has a short biological half-life of 1.5–2.5 h and a broad first-pass metabolism in the liver (67
Rufinamide is the preferred medication for management Lennox-Gastaut Syndrome (LGS). Its gradual absorption from the gastrointestinal pathway is due to its restricted solubility and slow dissolving rate in gastrointestinal fluids. The restricted bioavailability of Rufinamide leads to inadequate transportation of drug to the brain. This research article explains the formulation of Rufinamide-loaded nanocochleates using liposomes as the core structure. Liposomes were produced via the ethanol injection method and optimized using a Box-Behnken experimental design. The optimization considered three independent factors lipid quantity, cholesterol quantity, and stirring speed and two response parameters: particle size and encapsulation efficiency. The optimized liposomes have a particle size of 130.1 +/- 2.2 nm, a zeta potential of -13.3 +/- 0.96 mv, an encapsulation efficiency of 86.13 +/- 1.46% w/w and a drug release of 86.74 +/- 0.87% w/w respectively. The refined liposomes were later transformed into nanocochleates utilizing the trapping process. The nanocochleates were evaluated for several factors including particle size of 157.5 +/- 1.4 nm, zeta potential of -19.16 +/- 3.02 mv, encapsulation efficiency of 89.78 +/- 1.87% w/w and drug release of 80.39 +/- 0.73% w/w in over 24 hours. Thus, this innovative method may serve as an improved alternative therapy for Lennox Gastaut Syndrome.
Diabetic retinopathy (DR), a leading cause of vision impairment and blindness, poses significant challenges for ocular drug delivery due to barriers limiting drug penetration to the eye's posterior segment. This study aimed to develop and characterize nanostructured lipid carriers (NLCs) encapsulating curcumin, naringenin, and alpha-lactalbumin for sustained and targeted ocular delivery via topical administration in DR management. The NLCs exhibited a uniform particle size of 138.7 ± 2.6 nm, high encapsulation efficiency (∼97 %), and a stable zeta potential of -25.6 mV. Transmission electron microscopy confirmed their spherical morphology, and differential scanning validated successful drug incorporation. In vitro studies demonstrated sustained release (82-86 % over 24 h), while ex vivo trans-corneal permeation using goat corneas showed effective drug penetration (67-73 % within 12 h). In vivo efficacy was assessed in a diabetic rat model over four weeks, where NLC-treated groups showed significant reduction in rat vitreous VEGF levels and preserved retinal morphology without signs of edema or hemorrhage. The NLC-based eye drop formulation demonstrated sustained drug release, enhanced trans-corneal drug permeation, and a significant reduction in vitreous VEGF levels, offering a promising, non-invasive therapeutic strategy for diabetic retinopathy and other posterior segment ocular disorders. Although retinal drug concentrations were not quantified in this study, pharmacodynamic outcomes support the formulation's potential efficacy; future studies will include pharmacokinetic profiling to further substantiate these findings.
Curcumin is a well-known phenolic compound obtained from Curcuma Longa L. It is used popularly as an antioxidant, anti-inflammatory, antispasmodic, antithrombotic, anticancer as well as immune-modulator. In the last couple of years, few studies showed the usefulness of curcumin against Helicobacter pylori along with the potential to restore gastric damage. However, limited solubility, poor alkaline pH stability and flow property have rendered the industrial application of curcumin. The current research focuses to address this limitation by modifying the flow property using coating and two-step glidant mixing process and then converted into dosage form. Furthermore; to have reproducible and reliable results, flow property was investigated by the advance methodology- powder flow tester (PFT). Initially, curcumin powder was coated with HPMC and further mixed with glidant Sodium Stearyl Fumarate by two methods viz. one-step and two-steps mixing operation. Both blends were investigated for various parameters viz. flow function test, wall friction test and bulk density. We found that a two-step glidant mixing operation to coated curcumin enhanced powder to flow significantly more than one-step. In the lateral stage, both blends were converted into gastroretentive tablets by using the direct compression method. Tablets prepared by using a two-step blend process showed more satisfactory results than one-steps with floating time of 24 h and 21 h respectively. Coating, two-step glidant mixing and PFT were found unique combined approach to prepare the direct compression tablet of curcumin, as it enables the industry to overcome production problems and ensure high-quality products.
Selegiline HCl (SGH) is MAO-B inhibitor with limited bioavailability due to extensive hepatic metabolism. Thus, this work aims to formulate and evaluate SGH loaded intranasal thermoreversible cubosomal gel in order to enhance its bioavailability and ensure efficient brain targeting. Experimental design and Artificial Neural Network (ANN) were explored to optimize the formulation. Gellan gum and konjac gum were used as gelling agent and mucoadhesive agent respectively to formulate mucoadhesive in situ nasal gel. Optimized formulation of SGH loaded cubosomal dispersion exhibits average particle size (166.8 f 3.12 nm), entrapment efficiency (72.85 f 1.50 %), and drug release at 6 h (89.15 f 1.04 %). In vitro drug release analysis demonstrated the sustained release pattern. In vivo pharmacokinetic studies in Swiss Albino mice showed approximately 1.90-fold increase in C max and AUC (0-t) in brain after intranasal administration. The C max and AUC for drug solution was found to be 4.3828 f 0.02 ng/mL, 19.4166 f 0.06 ng min/mL and for cubosomal gel it was 11.7665 f 0.32 ng/ mL, 36.9216 f 0.41 ng min/mL respectively. Furthermore, the stability study was executed for estimation of shelf life of optimized formulation. The shelf life of SGH loaded cubosmal gel was found to be 20.64 months which demonstrate its long-term stability. The in vitro and in vivo evaluation endorsed that the fabricated cubosomal in situ nasal gel could be the promising approach for nose to brain delivery of SGH in Parkinson's therapy.
INTRODUCTION:The objective of the reported work was to develop Montelukast sodium (MS) solid lipid nanoparticles (MS-SLNs) to ameliorate its oral bio-absorption. Herein, the highpressure homogenization (HPH) principle was utilized for the fabrication of MS-SLNs. METHOD:The study encompasses a 23 full factorial statistical design approach where mean particle size (Y1) and percent entrapment efficiency (Y2) were screened as dependent variables while, the concentration of lipid (X1), surfactant (X2), and co-surfactant (X3) were screened as independent variables. The investigation of MS-SLNs by DSC and XRD studies unveiled the molecular dispersion of MS into the SLNs while TEM study showed the smooth surface of developed MSSLNs. The optimized MS-SLNs exhibited mean particle size (MPS) = 115.5 ± 1.27 nm, polydispersity index (PDI) = 0.256 ± 0.04, zeta potential (ζ) = -21.9 ± 0.32 mV and entrapment efficiency (EE) = 90.97 ± 1.12 %. The In vivo pharmacokinetic study performed in Albino Wistar rats revealed 2.87-fold increments in oral bioavailability. RESULTS:The accelerated stability studies of optimized formulation showed good physical and chemical stability. The shelf life estimated for the developed MS-SLN was found to be 22.38 months. CONCLUSION:At the outset, the developed MS-SLNs formulation showed a significant increment in oral bioavailability and also exhibited excellent stability in exaggerated storage conditions.
In recent years, quantum dots (QDs) have emerged as a promising nanomaterial with the potential to revolutionize diagnostic applications due to their unique optical and electrical capabilities. In this setting, there has been a lot of interest in incorporating QDs into composite structures to create cutting-edge diagnostic tools and methods. This summary summarizes the present status of diagnostic composites based on Quantum Dots. It describes the fundamentals of QDs and how their fluorescence can be tuned and their properties vary depending on their size, making them promising candidates for sensitive and multiplexed detection. The synthesis, functionalization, and applications of QDs-based composites across multiple diagnostic platforms are all covered in this article. Their importance in improving the efficiency of in vitro and in vivo diagnostic techniques, such as biosensing, immunoassays, cellular imaging, and targeted drug delivery, is highlighted in particular. The difficulties and factors related to QDs-based composites' biocompatibility, toxicity, and clinical translation are also discussed in the abstract. Overall, this chapter highlights the revolutionary potential of Quantum Dots based composites in diagnostics, allowing for more precise, efficient, and individual monitoring of disease.
The solidification of deep eutectic solvent (DES) through wet impregnation techniques on inert solid carriers is an interesting approach that offers better processing attributes and excellent stability. Herein, DES of Fimasartan (FS) was developed to improve its solubility and bioavailability. The selected DES-FS was solidified by wet impregnation method employing Nesulin US2 and Aerosil 200. The SeDeM-SLA (solid-liquid adsorption) system was employed to investigate flow attributes of solidified DES-FS. Further, the selected solidified DES-FS (A) was characterized by Fourier transforms infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM). The DES comprising Choline Chloride (ChCl): Glycerol (Gly) (1:3) revealed maximum drug solubility (35.6 +/- 2.2 mg/mL) and thus opted for solidification. Solidification through wet impregnation was employed using 1:0.5 ratios (DES-FS to carriers). The Index of Good Flow (IGF) value was calculated from the SeDeM-SLA expert system, which indicates the better flow characteristics of solidified DES-FS, particularly with Neusilin US2 [SDES-FS (A)]. The solid-state evaluation data of SDS-FS (A) suggested a transition of FS to an amorphous form, resulting in an increment in solubility and dissolution. A similar trend was reported in the in vivo pharmacokinetic study, which indicated a 2.9 folds increment in the oral bioavailability of FS. Furthermore, excellent stability, i.e., a shelf life of 28.44 months, reported by SDES-FS (A) in accelerated stability studies, suggests better formulation perspectives. In a nutshell, the present study evokes the potentiality of performing solidification through wet impregnation and successful implementation of the SeDeM-SLA expert model, which could find wide applications in pharmaceutical science.