Formulation, characterization and in-vivo evaluation of standardized Tabernaemontana divericata extract hydrogel for wound healing.

BACKGROUND: Tabernaemontana divaricata (TD) from the Apocynaceae family exhibits traditional therapeutic properties such as anti-inflammatory, antioxidant, and acetylcholinesterase activity, etc. OBJECTIVE: To formulate and evaluate the wound healing potential of standardized ethanolic extract of TD leaves hydrogel on experimental models of wounds in Wistar rats with the design of experiment approach. METHODS: The prepared PVA-based hydrogel of TD extract was evaluated. In-vivo, wound healing activities using excision, incision, and burn wound models were performed concerning percent wound contraction, epithelialization period, tensile strength, and histological analysis. RESULTS: On the 20th day of the excision model, percentage wound contraction for 0.5 mg/ml and 1 mg/ml extract hydrogel was found to be 90.35 % ± 0.46 and 97.28 % ± 0.59, respectively, while on the 9th day of incision model, the tensile strength of both doses of hydrogel was found to be 191.16 ± 1.51 g and 201.00 ± 1.29 g, respectively, indicating that both concentrations of the hydrogel showed significant (P < 0.05) wound healing as compared to disease control and vehicle control group. The histopathological study of hydrogel showed no necrotic cells and a greater amount of collagen. Furthermore, in the burn wound model, both doses of TD hydrogel had significant wound-healing activity, as demonstrated by a reduction in the time needed for epithelialization and an increase in the rate of wound contraction (P < 0.05). CONCLUSION: The proposed formulation showed potential for wound healing and may be studied further in clinical trials.

PROTAC Beyond Cancer- Exploring the New Therapeutic Potential of Proteolysis Targeting Chimeras.

In the realm of oncology, the transformative impact of PROTAC (PROteolysis TAget-ing Chimeras) technology has been particularly pronounced since its introduction in the 21st cen-tury. Initially conceived for cancer treatment, PROTACs have evolved beyond their primary scope, attracting increasing interest in addressing a diverse array of medical conditions. This ex-panded focus includes not only oncological disorders but also viral infections, bacterial ailments, immune dysregulation, neurodegenerative conditions, and metabolic disorders. This comprehensive review explores the broadening landscape of PROTAC application, high-lighting ongoing developments and innovations aimed at deploying these molecules across a spectrum of diseases. Careful consideration of the design challenges associated with PROTACs reveals that, when appropriately addressed, these compounds present significant advantages over traditional therapeutic approaches, positioning them as promising alternatives. To evaluate the efficacy of PROTAC molecules, a diverse array of assays is employed, ranging from High-Throughput Imaging (HTI) assays to Cell Painting assays, CRBN engagement assays, Fluorescence Polarization assays, amplified luminescent proximity homogeneous assays, Time-resolved fluorescence energy transfer assays, and Isothermal Titration Calorimetry assays. These assessments collectively contribute to a nuanced understanding of PROTAC performance. Looking ahead, the trajectory of PROTAC technology suggests its potential recognition as a ver-satile therapeutic strategy for an expansive range of medical conditions. Ongoing progress in this field sets the stage for PROTACs to emerge as valuable tools in the multifaceted landscape of medical treatments.

Exploring modified chitosan-based gene delivery technologies for therapeutic advancements.

One of the critical steps in gene therapy is the successful delivery of the genes. Immunogenicity and toxicity are major issues for viral gene delivery systems. Thus, non-viral vectors are explored. A cationic polysaccharide like chitosan could be used as a nonviral gene delivery vector owing to its significant interaction with negatively charged nucleic acid and biomembrane, providing effective cellular uptake. However, the native chitosan has issues of targetability, unpacking ability, and solubility along with poor buffer capability, hence requiring modifications for effective use in gene delivery. Modified chitosan has shown that the "proton sponge effect" involved in buffering the endosomal pH results in osmotic swelling owing to the accumulation of a greater amount of proton and chloride along with water. The major challenges include limited exploration of chitosan as a gene carrier, the availability of high-purity chitosan for toxicity reduction, and its immunogenicity. The genetic drugs are in their infancy phase and require further exploration for effective delivery of nucleic acid molecules as FDA-approved marketed formulations soon.

Formulation and Development of Hyaluronic Acid based Gel with Ketoconazole-Loaded Nanostructured Lipid Carriers in Fungal Infection.

BACKGROUND: Ketoconazole is an imidazole ring containing antifungal agent used in the treatment of systemic fungal infections. It acts by blocking the synthesis of ergosterol, an essential component of the fungal cell membrane. OBJECTIVE: The purpose of this work is to construct skin targeting ketoconazole nanostructured lipid carriers (NLCs) loaded hyaluronic acid (HA) modified gel to minimize side effects and provide a controlled release. METHODS: The NLCs were prepared using emulsion sonication method and their optimized batches were characterized for X-ray diffraction, scanning electron microscopy and fourier transform infrared spectroscopy study. These batches were then incorporated into HA containing gel for convenient application. The final formulation was compared with the marketed formulation for studying its antifungal activity and drug diffusion. RESULTS: Ketoconazole NLCs loaded hyaluronic acid formulation was successfully developed with desirable formulation parameters by using 23 Factorial design. In vitro release study of developed formulation showed prolonged drug release (up to 5 hrs) while ex vivo drug diffusion study on human cadaver skin showed better drug diffusion as compared with marketed formulation. Moreover, the release study and diffusion study results reflected the improvement of antifungal activity of the developed formulation against Candida albicans. CONCLUSION: The work suggests that ketoconazole NLCs loaded HA modified gel provides prolonged release. The formulation also has good drug diffusion and antifungal activity and thus can act as a promising carrier for topical delivery of ketoconazole.

Formulation Development and Evaluation of Indian Propolis Hydrogel for Wound Healing.

Flavonoids and polyphenolic compounds play a key role in wound healing cycle modulation. Propolis, a natural bee product, has been widely reported as an enriched source of polyphenols and flavonoids as important chemical constituents and for its wound healing potential. The goal of this study was to develop and characterize a propolis-based polyvinyl alcohol (PVA) hydrogel composition with wound healing potential. To understand the impacts of critical material attributes and process parameters, formulation development was carried out using a design of experiment approach. A preliminary phytochemical analysis of Indian propolis extract showed the presence of flavonoids (23.61 ± 0.0452 mg equivalent of quercetin/g) and polyphenols (34.82 ± 0.0785 mg equivalent of gallic acid/g), both of which aid in wound healing and skin tissue regeneration. The pH, viscosity, and in vitro release of the hydrogel formulation were also studied. The burn wound healing model results revealed significant (p < 0.0001) wound contraction by propolis hydrogel (93.58 + 0.15%) with rapid re-epithelialization relative to 5% w/w povidone iodine ointment USP (Cipladine®) (95.39 + 0.16%). The excision wound healing model confirms significant (p < 0.0001) wound contraction by propolis hydrogel (91.45 + 0.29%) with accelerated re-epithelialization comparable to 5% w/w povidone iodine ointment USP (Cipladine®) (94.38 + 0.21%). The developed formulation offers promise for wound healing, which may be investigated further for clinical research.

Functional Thermoresponsive Hydrogel Molecule to Material Design for Biomedical Applications.

Temperature-induced, rapid changes in the viscosity and reproducible 3-D structure formation makes thermos-sensitive hydrogels an ideal delivery system to act as a cell scaffold or a drug reservoir. Moreover, the hydrogels' minimum invasiveness, high biocompatibility, and facile elimination from the body have gathered a lot of attention from researchers. This review article attempts to present a complete picture of the exhaustive arena, including the synthesis, mechanism, and biomedical applications of thermosensitive hydrogels. A special section on intellectual property and marketed products tries to shed some light on the commercial potential of thermosensitive hydrogels.

Progress on Thin Film Freezing Technology for Dry Powder Inhalation Formulations.

The surface drying process is an important technology in the pharmaceutical, biomedical, and food industries. The final stage of formulation development (i.e., the drying process) faces several challenges, and overall mastering depends on the end step. The advent of new emerging technologies paved the way for commercialization. Thin film freezing (TFF) is a new emerging freeze-drying technique available for various treatment modalities in drug delivery. TFF has now been used for the commercialization of pharmaceuticals, food, and biopharmaceutical products. The present review highlights the fundamentals of TFF along with modulated techniques used for drying pharmaceuticals and biopharmaceuticals. Furthermore, we have covered various therapeutic applications of TFF technology in the development of nanoformulations, dry powder for inhalations and vaccines. TFF holds promise in delivering therapeutics for lung diseases such as fungal infection, bacterial infection, lung dysfunction, and pneumonia.

Formulation Development of Folic Acid Conjugated PLGA Nanoparticles for Improved Cytotoxicity of Caffeic Acid Phenethyl Ester.

BACKGROUND: Honey bee propolis is one of the natural products reported in various traditional systems of medicines, including Ayurveda. Caffeic acid phenethyl ester (CAPE) is an active constituent of propolis which is well known for its anticancer potential. The therapeutic effects of CAPE are restricted owing to its less aqueous solubility and low bioavailability. OBJECTIVE: In this study CAPE loaded folic acid conjugated nanoparticle system (CLFPN) was investigated to enhance solubility, achieve sustained drug release, and improved cytotoxicity of CAPE Methods: Formulation development, characterization, and optimization were carried out by the design of experiment approach. In vitro and in vivo cytotoxicity study was carried out for optimized formulations. RESULTS: Developed nanoparticles showed particle size and encapsulation efficiency of 170 ± 2-195 ± 3 nm and 75.66 ± 1.52-78.80 ± 1.25%, respectively. Optimized formulation CLFPN showed sustained drug release over a period of 42 h. GI50 concentration was decreased by 46.09% for formulation compared to CAPE in MCF-7 cells, indicating the targeting effect of CLFPN. An improved in vitro cytotoxic effect was reflected in the in vivo Daltons Ascites Lymphoma model by reducing tumor cell count. CONCLUSION: The desired nanoparticle characteristic with improved in vivo and in vitro cytotoxicity was shown by the developed formulation. Thus it can be further investigated for biomedical applications.

Standardization, anti-carcinogenic potential and biosafety of Indian propolis.

BACKGROUND: Propolis from apiculture is known for wide range of medicinal properties owing to its vast chemical constituents including polyphenols, flavonoids and anticancer agent Caffeic acid phenethyl ester (CAPE). OBJECTIVES: The objective of the study was to extract and standardize Indian propolis (IP) with respect to selected markers by newly developed High performance liquid chromatography (HPLC) method, to evaluate in vitro and in vivo anticancer activity and biosafety of Indian propolis. MATERIALS AND METHODS: IP was extracted, optimized and standardized using a newly developed and validated HPLC method for simultaneous estimation of caffeic acid, apigenin, quercetin and CAPE. The standardised ethanolic extract of IP (EEIP) was screened for in vitro cytotoxicity using sulforhodamine B (SRB) assay, in vivo anti-carcinogenic effect against Dalton's Lymphoma ascites (DLA) cells, hemolytic effect and pesticide analysis. RESULTS: The EEIP was found to contain more amount of total flavonoids (23.61 ± 0.0452 mg equivalent of quercetin/g), total polyphenolics (34.82 ± 0.0785 mg equivalent of gallic acid/g) and all selected markers except caffeic acid compared to all other extracts. EEIP showed better anti-cancer potential than CAPE on MCF-7 and HT-29 cell line and significant (p < 0.01) in vivo anti-carcinogenic effects against DLA in comparison with 5-fluorouracil. EEIP was found to be non-hemolytic. CONCLUSION: From in vitro cytotoxicity, in vivo anti-carcinogenicity and biosafety studies it can be concluded that the standardized EEIP is safe and can be considered for further development as a biomedicine.

Development of plumbagin-loaded phospholipid-Tween® 80 mixed micelles: formulation, optimization, effect on breast cancer cells and human blood/serum compatibility testing.

BACKGROUND: Phospholipid and Tween(®) 80 mixed micelles were investigated as injectable nanocarriers for the natural anticancer compound, plumbagin (PBG), with the aim to improve anticancer efficiency. PBG-loaded mixed micelles were fabricated by self-assembly; composition being optimized using 3(2) factorial design. RESULTS & DISCUSSION: Optimized mixed micelles were spherical and 46 nm in size. Zeta potential, drug loading and encapsulation efficiency were 5.04 mV, 91.21 and 98.38% respectively. Micelles demonstrated sustained release of PBG. Micelles caused a 2.1-fold enhancement in vitro antitumor activity of PBG towards MCF-7 cells. Micelles proved safe for intravenous injection as PBG was stable at high pH; micelle size and encapsulation efficiency were retained upon dilution. CONCLUSION: Developed mixed micelles proved potential nanocarriers for PBG in cancer chemotherapy.