Development of Lipid Polymer Hybrid Nanoparticles of Abietic Acid: Optimization, In-Vitro and Preclinical Evaluation.

The objective of the current research was to develop abietic acid (AA)-loaded hybrid polymeric nanoparticles (HNPs) for anti-inflammatory and antioxidant activity after oral administration. AAHNPs were developed by microinjection technique and optimized by 3-factor 3-level Box-Behnken design. The AAHNPs were evaluated for morphology, FTIR, X-ray diffraction, in-vitro release, ex-vivo permeation, in-vitro antioxidant, and in-vivo anti-inflammatory activity. The optimized AAHNPs (AAHNPsopt) displayed 384.5 ± 6.36nm of PS, 0.376 of PDI, 23.0 mV of ZP, and 80.01 ± 1.89% of EE. FTIR and X-ray diffraction study results revealed that AA was encapsulated into a HNPs matrix. The AAHNPsopt showed significant (P < 0.05) high and sustained release of AA (86.72 ± 4.92%) than pure AA (29.87 ± 3.11%) in 24h. AAHNPsopt showed an initial fast release of AA (20.12 ± 3.07% in 2h), which succeeded in reaching the therapeutic concentration. The AAHNPsopt showed 2.49-fold higher ex-vivo gut permeation flux than pure AA due to the presence of lipid and surfactant. The AAHNPsopt exhibited significantly (P < 0.05, P < 0.01, P < 0.001) higher antioxidant activity as compared to pure AA at each concentration. AAHNPsopt formulation displayed a significantly (P < 0.05) higher anti-inflammatory effect (21.51 ± 2.23% swelling) as compared to pure AA (46.51 ± 1.74% swelling). From the in-vitro and in-vivo finding, it was concluded that HNPs might be a suitable carrier for the improvement of the therapeutic efficacy of the drug.

Development and Optimization of Hybrid Polymeric Nanoparticles of Apigenin: Physicochemical Characterization, Antioxidant Activity and Cytotoxicity Evaluation.

Breast cancer is the most common cancer in females and ranked second after skin cancer. The use of natural compounds is a good alternative for the treatment of breast cancer with less toxicity than synthetic drugs. The aim of the present study is to develop and characterize hybrid Apigenin (AN) Nanoparticles (NPs) for oral delivery (AN-NPs). The hybrid AN-NPs were prepared by the self-assembly method using lecithin, chitosan and TPGS. Further, the NPs were optimized by Box-Behnken design (3-factor, 3-level). The hybrid NPs were evaluated for particle size (PS), entrapment efficiency (EE), zeta potential (ZP), and drug release. The optimized hybrid NPs (ON2), were further evaluated for solid state characterization, permeation, antioxidant, cytotoxicity and antimicrobial study. The formulation (ON2) exhibited small PS of 192.6 ± 4.2 nm, high EE 69.35 ± 1.1%, zeta potential of +36.54 mV, and sustained drug release (61.5 ± 2.5% in 24 h), as well as significantly (p < 0.05) enhanced drug permeation and antioxidant activity. The IC50 of pure AN was found to be significantly (p < 0.05) lower than the formulation (ON2). It also showed significantly greater (p < 0.05) antibacterial activity than pure AN against Bacillus subtilis and Salmonella typhimurium. From these findings, it revealed that a hybrid AN polymeric nanoparticle is a good carrier for the treatment of breast cancer.

Development and evaluation of phytosome-loaded microsphere system for delivery of ginseng extract.

The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential through enhancing the Ginsenoside Rb1(GRb1) bioavailability (BA). Phytosome complexes (F1, F2, and F3) were prepared by reacting GE with phospholipids in disparate ratios. F3 was chosen for preparing the phytosomes powder (PP) and phytosomes-loaded microspheres (PMs). Extract microspheres (EMs) were prepared by the addition of extract directly into the same polymer mixture. F3 gave enhanced entrapment efficiency (50.61%, w/w) along with spherical-shaped particle size (42.58 ± 1.4 nm) with the least polydispersity index (0.193 ± 0.01). PM showed an enhanced relative bioavailability (157.94%) of GRb1. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold. It was concluded that the PM system might be an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathy.

Formulation of carteolol chitosomes for ocular delivery: formulation optimization, ex-vivo permeation, and ocular toxicity examination.

Background:Conventional delivery systems like solution and suspension are commonly used for the treatment of ocular diseases but have low corneal residence time and hence the duration of effect is limited. These drawbacks of conventional systems can be reduced by preparing bioadhesive chitosan (CH) coated noisome.Methods: Niosomes (NIM) of carteolol (CT) were developed by the thin-film hydration method and optimised by the Box-Behnken statistical design. Further, the optimised CT-NIM was coated with CH to enhance the ocular residence time . The optimised formulation was evaluated for vesicle size, entrapment efficiency, and in-vitro drug release and transcorneal permeation, histopathology, etc.Results: CT-NIM-opt showed the vesicle size and entrapment efficiency of 235 ± 3.54 nm, and 70.45 ± 0.87%, respectively. DSC spectra exhibited that CT was completely encapsulated into the CH-CT-NIM matrix. Drug release from CH-CT-NIM-opt was more sustained (68.28 ± 4.2%) than CT-NIM (75.69 ± 4.5% in 12 h) and CT solution (99.89 ± 2.8% in 4 h). The CH-CT-NIM-opt represented a strong bio-adhesion (89.76 ± 3.6%) than CT-NIM-opt (15.65 ± 3.4%). The permeation flux exhibited 1.13-fold higher permeation than CT-NIM and 3.23 fold than CT solution. The corneal hydration was found to be within the limit value. The histopathology study exhibited no structural damage to the cornea . HET-CAM results showed zero scores indicating no bleeding or haemorrhage. CH-CT-NIM-opt was found to be isotonic and exhibited good stability when stored at 4 °C for the stated duration of time.Conclusion: The above findings suggested that NIM can be a potential carrier for the delivery of CT with better ocular residence time.

Formulation of Chitosan-Coated Piperine NLCs: Optimization, In Vitro Characterization, and In Vivo Preclinical Assessment.

In the present research work, surface-modified nanostructured lipid carriers (NLCs) with chitosan (CH) were prepared to improve the therapeutic efficacy of piperine (PP). NLCs were developed and optimized (CH-PP-NLCs-opt) by design expert software and the selected NLCs surface was coated with chitosan (0.2% w/v). CH-PP-NLCs-opt have shown a particle size of 149.34 ± 4.54 nm and entrapment efficiency of 80.65 ± 1.23%. The results of the solid-state characterization study exhibited that PP enclosed in lipids and present amorphous form. It might be due to the nanoparticle size of NLCs. The drug release study revealed PP-NLCs-opt and CH-PP-NLCs-opt exhibited significant (P < 0.05) difference in PP release (88.87 ± 5.23% and 76.34 ± 4.54%) as compared to pure PP (19.02 ± 2.87%). CH-PP-NLCs-opt exhibited strong bioadhesion than PP-NLCs-opt which has a positive influence the drug permeation and absorption. CH-PP-NLCs-opt showed higher permeation (1083.34 ± 34.15 µg/ cm2) than pure PP (106.65 ± 15.44 µg/cm2) and PP-NLCs-opt (732.45 ± 28.56 µg/ cm2). The significantly enhanced bioavailability of PP was observed from CH-PP-NLCs-opt (3.76- and 1.21-fold) than PP-dispersion and PP-NLCs-opt. The diabetes was induced in rats by a single intraperitoneal administration of streptozotocin (STZ, 40 mg/kg, citrate buffer pH 4.5), and results revealed that PP-NLCs-opt and CH-PP-NLCs-opt reduce the blood glucose level (28.26% and 36.52% respectively) as compared to PP-dispersion (10.87%). It also helps to maintain the altered biochemical parameters. In conclusion, CH-PP-NLC can be a novel oral nanocarrier for the management of diabetes.

A Comprehensive Review on Current Treatments and Challenges Involved in the Treatment of Ovarian Cancer.

Ovarian cancer (OC) is the second most common gynaecological malignancy. It typically affects females over the age of 50, and since 75% of cases are only discovered at stage III or IV, this is a sign of a poor diagnosis. Despite intraperitoneal chemotherapy's chemosensitivity, most patients relapse and face death. Early detection is difficult, but treatment is also difficult due to the route of administration, resistance to therapy with recurrence, and the need for precise cancer targeting to minimize cytotoxicity and adverse effects. On the other hand, undergoing debulking surgery becomes challenging, and therapy with many chemotherapeutic medications has manifested resistance, a condition known as multidrug resistance (MDR). Although there are other therapeutic options for ovarian cancer, this article solely focuses on co-delivery techniques, which work via diverse pathways to overcome cancer cell resistance. Different pathways contribute to MDR development in ovarian cancer; however, usually, pump and non-pump mechanisms are involved. Striking cancerous cells from several angles is important to defeat MDR. Nanocarriers are known to bypass the drug efflux pump found on cellular membranes to hit the pump mechanism. Nanocarriers aid in the treatment of ovarian cancer by enhancing the delivery of chemotherapeutic drugs to the tumour sites through passive or active targeting, thereby reducing unfavorable side effects on the healthy tissues. Additionally, the enhanced permeability and retention (EPR) mechanism boosts the bioavailability of the tumour site. To address the shortcomings of conventional delivery, the current review attempts to explain the current conventional treatment with special reference to passively and actively targeted drug delivery systems (DDSs) towards specific receptors developed to treat ovarian cancer. In conclusion, tailored nanocarriers would optimize medication delivery into the intracellular compartment before optimizing intra-tumour distribution. Other novel treatment possibilities for ovarian cancer include tumour vaccines, gene therapy, targeting epigenetic alteration, and biologically targeted compounds. These characteristics might enhance the therapeutic efficacy.

Exploring the wound healing activity of phytosomal gel of Annona squamosa and Cinnamomum tamala leaves ethanolic extracts with antioxidant and antimicrobial activities in S aureus infected excision wound model.

Wound healing is a natural process but it is impaired in certain conditions like age, stress, health, immunity status and microbial infection. Particularly in cases of chronic wounds, infection is nearly often the main and unavoidable obstacle to wound healing. For this purpose, leaves of Annona squamosa and Cinnamomum tamala were selected based on their ethnopharmacological uses and reported pharmacological activities. The ethanolic extracts of both plant parts i.e. ethanolic extracts of Annona squamosa (ASEE) and Cinnamomum tamala (CTEE) were evaluated for their antioxidant and antimicrobial activities individually as well as in 1:1 combination as Polyherbal Ethanolic extract (PHEE). In our previous work both these ethanolic extracts were combined and phytosomes were prepared by thin layer hydration method and optimized for vesicle size and entrapment efficiency. The phytosomes were then incorporated into Carbopol gel matrix. In this present study the selected phytosomal gel was tested in two different concentrations (2% and 5%) for in vivo wound healing activity using S. aureus infected excision wound model. The various parameters examined were percentage wound contraction, epithelization period, bacteriological quantification, biochemical parameters like Superoxide dismutase (SOD), Catalase and hydroxyproline. The PHEE exhibited synergistic antioxidant activity. The PHEE also showed enhanced antimicrobial activity against bacteria namely gram-positive S. aureus, gram-negative E. Coli. The phytosomal gel showed increased wound contraction, reduced time of epithelization, increased hydroxyproline content, increased levels of SOD and Catalase enzymes and reduced bacterial load when compared with Povidone iodine ointment as standard in S. aureus infected excision wound model.

The Anti-ulcer Potential of Weissella cibaria Assisted Bio-fermented Product of Citrus limetta Waste Peel in Wistar Albino Rats.

BACKGROUND: There are patents available related to fermented food and beverages which enhance to human health. Citrus limetta (Mosambi) has a high content of flavonoids and exhibits antioxidant activity, which could stimulate the digestive system and be useful for gastroprotective activity. It supports digestion by neutralizing the acidic digestive juices and reducing gastric acidity. OBJECTIVE: This study explored the potential of using waste peel extract from Citrus limetta to prevent ulcers. The study specifically sought to assess the anti-ulcer properties of fermented and non-fermented extracts and compare them. Further, the study looked at the potential benefits of treating or preventing ulcers with Citrus limetta waste peels and whether fermentation affected the efficacy of the treatment. METHODS: Thirty female Wistar albino rats were equally distributed into five different groups. Group 1 received distilled water (20 ml/kg/b.w); Group 2 received indomethacin (mg/kg/b.w); Group 3 received omeprazole (20 mg/kg/b.w); Group 4 received aqueous extract of Mosambi peel (400 mg/kg/b.w) and Group 5 received fermented product of extract of Mosambi peel (400 mg/kg/b.w). RESULTS: Findings explored that, compared to non-fermented citrus fruit juice, biofermented exhibited less gastric volume (1.58 ± 0.10 ml vs. 1.8 ± 0.14 ml), reduced MDA levels (355.23 ± 100.70 µmol/mg protein vs. 454.49 ± 155.88 µmol/mg protein), and low ulcer index (0.49 ± 0.07 vs. 0.72 ± 0.14). CONCLUSION: The results suggest that the bio-fermented product of Citrus limetta peel has better anti-ulcer potential against peptic ulcer induced by indomethacin in Wistar albino rats compared to non-fermented.

Luteolin-loaded Invasomes Gel for Transdermal Delivery: Development, Optimization, in-vitro, and Preclinical Evaluation.

Luteolin (LN), is an herbal bioactive flavone and exhibits many pharmacological activities. However, the bioavailability of LN is limited due to its inadequate solubility and significant first-pass metabolism. The present study developed transdermal LN-loaded invasomes (IVM) gel to improve the therapeutic efficacy. The LN-IVM was prepared and optimized by 2 3 factorial designs. LN-IVM was characterized for physicochemical parameters. The optimized LN-IVM (LN-IVMopt) was incorporated into HPMC-K4M gel and evaluated for viscosity, spreadability, and irritation. Further LN-IVM gel was evaluated for drug release, ex-vivo permeation, pharmacokinetic and pharmacodynamics study. LN-IVMopt showed 300.8±2.67 nm of VS, 0.258 of PDI, 89.92±1.29% of EE, and a zeta potential of -18.2 mV. LN-IVM exhibited spherical morphology. FTIR and XRD results demonstrated that LN was encapsulated into IVM matrix. The optimized IVM gel (LN-IVMoptG2) exhibited excellent viscosity, spreadability, and sustained release of LN (91.32±2.95% in 24 h). LN-IVMoptG2 exhibited statistically significant (p < 0.05) higher flux (5.79 µg/h/cm2 ) than LN-gel (2.09 µg/h/cm2 ). The apparent permeability coefficient of plain LN gel and LN- IVMoptG was 1.15×10-5 cm/min and 3.22×10-5 cm/min respectively. LN-IVMoptG2 showed no irritation (score 0.0) throughout the study (60 min). The relative bioavailability of LN from LN-IVMopt-G2 (transdermal) was 2.38±0.19 fold as compared to LN-Sus (oral) and 1.81±0.15-fold than plain LN-gel (transdermal). The LN-IVMoptG2 showed a substantial lessening in the paw volume up to 12 h (17.48±1.94% swelling) than plain LN-gel (44.77±2.82% swelling). The finding concluded that the IVM gel is a novel, effective, and safe approach for the delivery of LN transdermally to improve its therapeutic efficacy.

Nanogels as Drug Delivery Carrier: A Narrative Review on Formulation Techniques, Characterization, Applications, and Patents.

Under the umbrella of targeted drug delivery systems, several techniques are unleashed in the market that allow a drug or other pharmacologically active material to be delivered to the target cell to treat a condition or health problem. The improvement of the pharmaceutical delivery systems' effectiveness, safety, and stability is accomplished through the Formulation of the nano-gel-based delivery system. Nanogels are aqueous dispersions of submicronsized, three-dimensional, strongly cross-linked networks of hydrophilic polymers that are inflated by water. Through a variety of delivery routes, such as oral, pulmonary, nasal, parenteral, and intraocular, an active pharmaceutical agent or therapeutic agent with a high or low molecular weight can be easily encapsulated into nanogels. Nanogels have been researched as drug delivery systems due to their beneficial qualities, such as biocompatibility, high stability, flexible particle size, drug loading capacity, and potential surface modification for active targeting by attaching ligands that recognize cognate receptors on target cells or tissues. By responding to internal or external stimuli, including pH, temperature, light, and redox, nano gels can be made to be stimulus-responsive, allowing for regulated drug release. Thus, in the fact of said characteristics' of nano gels, this review manuscript aims to provide an overview of characterization, evaluation, formulation technique, recent applications, and patents of nano gels.