Polyethylene Glycol-Based Polymer-Drug Conjugates: Novel Design and Synthesis Strategies for Enhanced Therapeutic Efficacy and Targeted Drug Delivery.

Due to their potential to enhance therapeutic results and enable targeted drug administration, polymer-drug conjugates that use polyethylene glycol (PEG) as both the polymer and the linker for drug conjugation have attracted much research. This study seeks to investigate recent developments in the design and synthesis of PEG-based polymer-drug conjugates, emphasizing fresh ideas that fill in existing knowledge gaps and satisfy the increasing need for more potent drug delivery methods. Through an extensive review of the existing literature, this study identifies key challenges and proposes innovative strategies for future investigations. The paper presents a comprehensive framework for designing and synthesizing PEG-based polymer-drug conjugates, including rational molecular design, linker selection, conjugation methods, and characterization techniques. To further emphasize the importance and adaptability of PEG-based polymer-drug conjugates, prospective applications are highlighted, including cancer treatment, infectious disorders, and chronic ailments.

Variations in human pulmonary fissures and lobes: a study conducted in nepalese cadavers.

The fissures of lungs are embryologically separating the bronchopulmonary segments, which later on persist in interlobar planes of fully developed lung. Fifty lungs (23 right side and 27 left side), obtained during routine dissection and preserved in formalin constituted the material for present study. In them, variations in fissures and lobes of lung were observed and compared with the previous studies. Seven right sided and 14 left sided lungs showed incomplete oblique fissure. Incomplete horizontal fissure of right lung was observed in eight lungs while it was completely missing in three specimens. A right lung with "lobe of the azygos vein" separated by a supernumerary fissure in medial surface was found. One of the right lung had both superior accessory fissure and inferior accessory fissure and four other right lungs and one left lung presented only with inferior accessory fissure. A vertical notch was found in middle lobe of one right lung. Eight left lungs exhibited with left minor fissure among them two lungs had lingula appearing as a separate lobe. Knowledge of variations in fissures and lobes is of interest to all medical professionals to exactly interpret radiographs, computed tomography scans, to diagnose, plan and modify a surgical procedure depending on the merit of the case and also in certain classical clinical cases pertaining to lung pathologies.

Advances in the Delivery of Cancer Therapeutics: A Comprehensive Review.

BACKGROUND: The effects of various chemotherapeutic agents have been assessed for their capacity to inhibit the cell replication in variety of cancer cases. At present there are more than hundred chemotherapeutic agents capturing worth 42 billion dollar of drug market. The major obstacle in the successful treatment of cancer is the obnoxious side effects of chemotherapeutics and multi drug resistance, which deteriorates the quality of life of cancer patient. OBJECTIVE: This article attempts to summarize different novel chemotherapeutic delivery systems which aim to circumvent these unwanted effects. Areas Covered: Outcomes of different tumor directed carrier systems have been discussed with special emphasis on nanocarriers systems, drug polymer conjugation, directly implantable matrices and others. In addition, combination therapy and immunotherapy are also discussed as a revolutionary alternative. CONCLUSION: Even though significant contributions have been made in the development of carrier systems for the chemotherapeutic agents, merits and demerits of all the avenues should be critically examined. Potential of all novel strategies should be exploited by critically evaluating their strength, weakness, opportunities and threats. Further, clinical trials based on revised and critically scrutinized frameworks and protocols are needed so that the efficiency and safe action of these new systems can be guaranteed in cancer patients.

Synthesis and oral hypoglycemic effect of novel thiazine containing trisubstituted benzenesulfonylurea derivatives.

A new series of 3-(4-substituted phenyl)-1-(4-(4,6-dimethyl-6H-1,3-thiazin-2-yl)phenylsulfonyl)-1-substituted urea (5a-o) was synthesized by an effectual route via sulfonylcarbamates and explores the novel site for substitution in sulfonylurea as well as the way of thiazine can be prepared. The molecules were established by elemental analysis and spectroscopic viz. IR, (1)H NMR, (13)C NMR and MS techniques. All the fifteen derivatives were shown very prominent oral hypoglycemic effect at the dose of 40 mg/kg body weight (p.o.) in respect of standard drug glibenclamide and control. The hypoglycemic effect was studied using oral glucose tolerance test in normal and NIDDM in STZ-rat model. The compounds 5a, 5d, 5f, 5i, 5k and 5n were dominant out of fifteen derivatives for blood glucose lowering activity (more than 80%) when comparing with NIDDM control. These derivatives were either containing simply phenyl ring (5a, 5f and 5k) on to the second amine of sulfonylurea (R' = H) or nitro group at the para position in compound 5d, 5i and 5n (R' = NO2 ) to produce significant oral hypoglycemic effect. Other structural activity relationship is also observed regarding the heteroaromatic and substituted aromatic group at R and R' position respectively.

Promotion and computation of inhibitory effect on tyrosinase activity of herbal cream by incorporating indigenous medicinal plants.

Herbal cream imparts a chief role in regulating melanin production of skin. The phytoconstituents present in herbal cream impact biological functions of skin and contribute nutrients required for the healthy skin. In the present study, it was envisaged to prepare three batches of herbal cream (HC1, HC2 and HC3) containing ethanol extracts of Emblica officinalis (fruits), Daucus carota (root), Mangifera indica (leaves), Mentha arvensis (leaves), Terminalia arjuna (bark) and Cucumis sativus (fruits) and investigated the prepared cream for inhibitory effect on tyrosinase activity. The herbal cream was formulated by incorporating different ratio of extracts, by using cream base. Each formulation HC1, HC2 and HC3 were segregated into three different formulations (HC1.1, HC1.2, HC1.3, HC2.1, HC2.2, HC2.3, HC3.1, HC3.2 and HC3.3) by incorporating increasing ratio of extract in formulation. The HC3.2 cream produces highest tyrosinase inhibitory effect 65.23 +/- 0.07%, while the HC2.1 exhibited minimum tyrosinase inhibitory effect 26.19 +/- 0.08% compared to other prepared cream. Comparison of the inhibitory activity of the formulations demonstrated that the rank order was HC3.2 > HC3.3 > HC1.2 > HC1.3 > HC3.1 > HC1.1 > HC2.3 > HC2.2 > HC2.1. It has been observed from the result that the formulations of antityrosinase activity were not concentrate dependent. This finding suggests that decrease in antityrosinase activity of HC1 and HC3 might be considering that the incompatibility of the higher extract content with the base of cream. The HC3 produce the maximum inhibitory effects on tyrosinase activity might be due to higher level of polyphenol and flavonoids present in extracts.

In vitro techniques to assess the proficiency of skin care cosmetic formulations.

Cosmetics comprising either natural or synthetic components are used almost regularly and universally in different forms to enhance the beauty. The utmost disclosure of human membrane to sunlight and environmental pollution results in the exhibition of free radical, that react with deoxyribonucleic acid, proteins and fatty acids, causation oxidative destruction dysfunction of the antioxidant system. In skin, the formation of reactive oxygen species leads to skin diseases, predominantly cutaneous malignancies, immunosuppression, wrinkles, aging, etc., The human organism fosters a barrier practice against the destructive action of free radicals, comprising mostly of vitamins, carotenoids and enzymes. Cosmetic products are the best option to reduce skin disorders such as hyper pigmentation, skin aging, skin wrinkling and rough skin texture, etc., Hence in this review, we conferred various in vitro methods that are used for the development of novel cosmetic formulation. There is an expanding fascinate employing in vitro techniques because they are less time consuming, more cost-effective and lessen the participation of human volunteers.

Development, in vitro and in vivo characterization of Eudragit RL 100 nanoparticles for improved ocular bioavailability of acetazolamide.

Glaucoma is characterized by increased intra ocular pressure (IOP) which results in blindness if left untreated. Acetazolamide (ACZ) is used to treat glaucoma since long back. Since it is a Class IV drug [According to Biopharmaceutics Classification System (BCS)], so its topical delivery results in poor ocular bioavailability. Objective of the present study is to increase the topical ocular bioavailability and to sustain the release of drug for longer time. ACZ-loaded Eudragit® RL 100 nanoparticle suspension (ACZ-E-NPs) was prepared by the nanoprecipitation method. Ratio of organic to aqueous phase and composition of organic phase were altered to get the best formulation. Formulations prepared with acetone and methanol as organic phase were smallest in size. EE was in the range of 57.8% to 68.5%. According to drug release study almost all the formulations released 80% of drug in 8 h duration. The kinetics of drug release showed that the drug release pattern followed Higuchi's model (highest R2 values) and further it was fitted to the Korsemeyer-Peppas model, which showed the release was as per Fickian diffusion. IOP lowering effects of plain drug solution and ACZ-E-NPs were compared in adult male albino rabbits with a Riester Tonometer. The data revealed that the ACZ-E-NPs lower the IOP for longer time and of higher magnitude also. The difference was significant (p<0.001). Short-term stability study showed that none of the formulations was having remarked difference in their physicochemical properties after 6 months of storage at various temperatures.

Optimization of polymeric nano drug delivery system using 3(2) full factorial design.

This study investigated the utility of a 3(2) factorial design and optimization process for nanoparticle suspension prepared by two different polymers Eudragit(®) RS 100 and Eudragit (®) RL 100 respectively. Total 18 formulations (9 formulations with each polymer) were prepared by solvent displacement technique. In these designs, two factors namely polymer weight (X1) and Aq. phase volume (X2) were evaluated each at three levels and experimental trials were performed at all nine possible combinations. Polymer weight (X1) and aqueous phase volume (X2) were selected as independent variables and particle size (Y1), % entrapment (Y2), drug release at 12(th) hrs. (Y3) are chosen as depended variables. In case of 3(2) factorial design, a full-model polynomial equation was established by subjecting the transformed values of independent variables to multiple regression analysis, and contour plots were drawn using the equation. The derived polynomial equations for particle size and % drug entrapment were verified by check point formulation. The result showed a wide variation in the responses for both of the polymer. For RS 100 polymer, particle size was 112-350 nm, entrapment: 26-72%, drug release was 42- 89% at 12(th) hrs. and for RL 100 polymer, particle size was 114-390 nm, entrapment: 30-72%, drug release was 50-90% at 12(th) hrs. The application of factorial design yielded a statistically systematic approach for the formulation and optimization of nanoparticles with desired particle size and high entrapment efficiency and release profile. The results of the optimized formulations showed particle size 225 nm, 63% drug entrapment and 83% drug release for RS 100 polymer and particle size was 148 nm, drug entrapment was 57%, drug release was 80% for RL 100 polymer.