Comparative Study of In Situ Gel Formulation Based on the Physico-Chemical Aspect: Systematic Review.

In recent years, in situ gel delivery systems have received a great deal of attention among pharmacists. The in situ gelation mechanism has several advantages over ointments, the most notable being the ability to provide regular and continuous drug delivery with no impact on visual clarity. Bioavailability, penetration, duration, and maximum medication efficacy are all improved by this mechanism. Our review systematically synthesizes and discusses comparisons between three types of in situ gelling system according to their phase change performance based on the physicochemical aspect from publications indexed in the Pubmed, ResearchGate, Scopus, Elsevier, and Google Scholar databases. An optimal temperature-sensitive in situ gelling solution must have a phase change temperature greater than ambient temperature (25 °C) to be able to be readily delivered to the eye; hence, it was fabricated at 35 °C, which is the precorneal temperature. In a pH-sensitive gelling system, a gel develops immediately when the bio-stimuli come into contact with it. An in situ gelling system with ionic strength-triggered medication can also perhaps be used in optical drug-delivery mechanisms. In studies about the release behavior of drugs from in situ gels, different models have been used such as zero-order kinetics, first-order kinetics, the Higuchi model, and the Korsmeyer-Peppas, Peppas-Sahlin and Weibull models. In conclusion, the optimum triggering approach for forming gels in situ is determined by a certain therapeutic delivery application combined with the physico-chemical qualities sought.

Preparation and molecular interaction of organic solvent-free piperine pro-liposome from soy lecithin.

Pro-liposome is a type of drug delivery system (DDS) with numerous advantages as a stable material with various applicability for several pharmaceutical dosage forms, to effectively deliver the material to reach its target in the human body. Nevertheless, it is mostly designed by employing an organic solvent hence giving rise to safety issues. We have developed a method for the preparation of organic solvent-free liposomes composed of soy lecithin and cholesterol by highlighting the importance of temperature during the initial mixing process, a self-hydration of a thin layer spread film, and a spray-drying technique with a suitable excipient as the carrier. The method was successfully applied to prepare a stable pro-liposome containing 0.17% (w/w) of piperine with an encapsulation efficiency of 95.58 ± 2.91%. Moreover, the study revealed that a piperine molecule forms hydrophobic interaction with six of the adjacent phospholipids in the liposome structure, this information can be useful for researchers designing similar studies. In conclusion, organic solvent-free pro-liposome can be an alternative method in the development of DDS, and several factors could be continuously improved to fulfill the intended pro-liposome characteristic.

Callyspongia spp.: Secondary Metabolites, Pharmacological Activities, and Mechanisms.

One of the most widespread biotas in the sea is the sponge. Callyspongia is a sponge genus found in the seas, making it easily available. In this review, the pharmacological activity and mechanism of action of the secondary metabolites of Callyspongia spp. are addressed, which may lead to the development of new drugs and targeted therapeutic approaches. Several scientific databases, such as Google Scholar, PubMed, ResearchGate, Science Direct, Springer Link, and Wiley Online Library, were mined to obtain relevant information. In the 41 articles reviewed, Callyspongia spp. was reported to possess pharmacological activities such as cytotoxicity against cancer cell lines (36%), antifungal (10%), anti-inflammatory (10%), immunomodulatory (10%), antidiabetic and antiobesity (6%), antimicrobial (8%), antioxidant (4%), antineurodegenerative (4%), antihypercholesterolemic (2%), antihypertensive (2%), antiparasitic (2%), antiallergic (2%), antiviral (2%), antiosteoporotic (2%), and antituberculosis (2%) activities. Of these, the antioxidant, antituberculosis, and anti-inflammatory activities of Callyspongia extract were weaker compared with that of the control drugs; however, other activities, particularly cytotoxicity, show promise, and the compounds responsible may be developed into new drugs.

Gelling Power Alteration on Kappa-Carrageenan Dispersion through Esterification Method with Different Fatty Acid Saturation.

The physicochemical properties of κ-carrageenan gels and their ester forms derived from different fatty-acid saturations were characterized and compared with those of native κ-carrageenan. Furthermore, stearic and oleic acids were used as the saturated and unsaturated fatty acids, respectively. Fourier-transform infrared (FTIR) spectra confirmed the introduction of the ester into the κ-carrageenan backbone. The thermogravimetric analysis showed that thermal stability increased along with the level of unsaturation, but there was a decrease in viscosity, hardness, and syneresis, which caused the consistency of the product to become more elastic. The results also showed that the ester form still has a swelling ability that is almost the same as that of κ-carrageenan. After being formulated into a gel dosage form, the product was successfully produced from the ester with unsaturated fatty acids, and it was more elastic than native κ-carrageenan and had good physical properties with spreadability that meets the requirements for topical preparations.

Nanoparticulate System for the Transdermal Delivery of Catechin as an Antihypercholesterol: In Vitro and In Vivo Evaluations.

Gambir (Uncaria gambir, Roxb.) contains catechins that is often empirically used to treat various diseases. Catechins can reduce cholesterol levels by inhibiting coenzyme HMG-CoA reductase that plays a role in cholesterol metabolism. Research has been carried out covering the optimization of transethosomal catechins, the formulation of Transethosomal Catechin Gel (TCG) and Non-Transethosomal Catechin Gel (NTCG), which were then tested for catechin permeation from these gel preparations in vitro using Franz's diffusion cell with PTFE membranes. The anti-hypercholesterol activity test was carried out with Simvastatin orally as a positive control using 25 male Wistar rats (Rattus norvegicus). The catechin transetosomes have a size of 176.1 ± 5.8 nm, Zeta potential -11.6 ± 5.28, and Entrapment Efficacy of 96.77% ± 0.05. The result of cumulative catechins that permeated from TCG and NTCG were and 172.454 ± 5.287 and 112.741 ± 2.241 µg respectively. Permeation test graphs showed similar permeation and flux profiles. TCG can reduce total cholesterol and LDL (Low Density Lipoprotein) values in rats by 39.77% and 51.52% respectively during 14 days of use.

Characteristic Comparison of an Intraoral Thin Film Containing Astaxanthin Nanoemulsion Using Sodium Alginate and Gelatin Polymers

Objectives: The present study was conducted to compare the characteristics of a thin film containing an astaxanthin-loaded nanoemulsion (TFANE) using two kinds of natural polymers, namely sodium alginate and gelatin. Materials and Methods: An astaxanthin nanoemulsion was prepared by using the self-nanoemulsifying method, followed by incorporation into a polymer matrix system by the solvent casting method to form TFANE. A characteristic comparison between the sodium alginate and gelatin matrix systems was carried out by comparing the physical and mechanical film properties. At the end of the study, in vitro dissolution tests were also assessed. Results: An intraoral film with good physical and mechanical properties containing an astaxanthin-loaded nanoemulsion was developed successfully using a natural polymer matrix system. The film, made from a gelatin matrix system containing an astaxanthin nanoemulsion, was more flexible and harder than films made from a sodium alginate matrix system, where all of the films have ideal characteristics for intraoral delivery. The dissolution test results showed that, with both sodium alginate and gelatin, more than 90% of the drug was released at 15 minutes. Conclusion: Gelatin as a natural polymer appears to be promising for the preparation of an intraoral thin film delivery system.

Caspase Cascade Activation During Apoptotic Cell Death of Human Lung Carcinoma Cells A549 Induced by Marine Sponge Callyspongia aerizusa.

INTRODUCTION: In this study, Callyspongia aerizusa (CA), one of the most popular marine sponges for cancer therapy research, was investigated for its phytochemical compounds and evaluated for its anticancer activity in various cell lines. Since lung cancer is the most frequently diagnosed cancer, a solution from this marine source is a good choice to address the resistance to anticancer agents. Elucidation of the underlying mechanism of cell death elicited by a CA extract in human lung carcinoma cells A549 was undertaken. METHODS: The presence of secondary metabolites in CA methanol extract was revealed by gas chromatography-mass spectrometry (GC-MS) and evaluated on four cancerous cell lines and a non-cancerous cell line using Cell Counting Kit-8. Since the activity of CA extract in A549 cells was then evaluated through clonogenic assay, morphological detection of apoptosis, polymerase chain reaction (PCR) and Western blot assay, were also presented in this study. RESULTS: GC-MS analysis revealed the presence of two ergosteroids, ergost-22-en-3-one, (5ß,22E), and ergost-7-en-3-ol, (35ß) in the sponge extract that was suggested to suppress A549 cells (IC50 9.38 µg/mL), and another cancerous cell's viability (IC50 3.12-10.72 µg/mL) in 24 h, but not in the non-cancerous cells. Moreover, CA extract was also able to reduce the colony-forming ability of A549 cells, and through A549 cells morphology seems that apoptosis is the underlying mechanism of cell death. Further, the treatment with CA extract induced the up-regulation of caspase-9, caspase-3, and PARP-1, and the down-regulation of BCL-2, in both mRNA and proteins expression level, promoting apoptotic cell death via caspase cascade. CONCLUSION: These findings suggest that the compounds in CA extract possess the ability to induce apoptotic cell death in A549 cells and could become a promising candidate for future anticancer therapy.

In situ ophthalmic gel forming systems of poloxamer 407 and hydroxypropyl methyl cellulose mixtures for sustained ocular delivery of chloramphenicole: optimization study by factorial design.

BACKGROUND: Conventional drug delivery systems have some major drawbacks such as low bioavailability, short residence time and rapid precorneal drainage. An in situ gel drug delivery system provides several benefits, such as prolonged pharmacological duration of action, simpler production techniques, and low cost of manufacturing. This research aims to get the optimum formula of chloramphenicol in situ gel based on the physical evaluation. METHODS: The effects of independent variables (poloxamer 407 and hydroxypropyl methyl cellulose (HPMC) concentration) on various dependent variables (gelling capacity, pH and viscosity) were investigated by using 32 factorial design and organoleptic evaluation was done with descriptive analysis. RESULTS: The optimized formula of chloramphenicol in situ gel yielded 9 variations of poloxamer 407 and HPMC bases composition in % w/v as follows, F1 (5; 0.45), F2 (7.5; 0.45), F3 (10; 0.45), F4 (5; 0.725), F5 (7.5; 0.725), F6 (10; 0.725), F7 (5; 1), F8 (7.5; 1), F9 (10; 1). The results indicated that the organoleptic, pH, and gelling capacity parameters matched all formulas (F1-F9), however, the viscosity parameter only matched F3, F6, F8, and F9. Based on factorial design, F6 had the best formula with desirability value of 0.54, but the design recommended that formula with the composition bases of poloxamer 407 and HPMC at the ratio of 8.16 % w/v and 0.77 % w/v, respectively, was the optimum formula with a desirability value of 0.69. CONCLUSION: All formulas have met the Indonesian pharmacopoeia requirements based on the physical evaluation, especially formula 6 (F6), which was supported by the result of factorial design analysis.

Antidiabetic activity of thin film containing astaxanthin-loaded nanoemulsion using carboxymethylcellulose sodium polymer on alloxan-induced diabetic rabbit.

The present study was conducted to evaluate the potency of thin film containing astaxanthin-loaded nanoemulsion (FDT-As-NE) in lowering blood glucose levels on alloxan-induced diabetic rabbit (ADR). Astaxanthin nanoemulsion (As-NE) was prepared using self-nanoemulsifying method, followed by incorporated into the carboxymethylcellulose sodium matrix polymer using a solvent casting method to form a thin film. The evaluation of FDT-As-NE was performed by chemical, physical, and mechanical characterizations. The administration of thin film was done by an intraoral route. New Zealand albino rabbits were induced with alloxan to get experimental diabetic animals. The antidiabetic activity was carried out in three groups of treatment. Group I was ADR treated by FDT-As-NE, Group II was ADR treated by pure astaxanthin, while Group III was normal control. The measurement of fasting means blood glucose levels was carried out in 0 days (before treatment) and after 14 days of treatment. The histopathological analysis of the pancreas was also examined. Data were statistically evaluated using Kruskal-Wallis statistical test. P < 0.05 was considered statistically significant. FDT-As-NE had good physical and mechanical characteristics that suitable for intraoral administration. Group I reduced elevated blood glucose levels compared to Group II (P < 0.01). Histopathological examination of pancreatic tissue for a Group I showed the normal condition of pancreatic ß-cell, suggesting the absence of any pathological lesions. These results suggest that thin film containing astaxanthin-loaded nanoemulsion administered by an intraoral route potentially useful for reducing glucose levels.

Physical study of Chloramphenicol In Situ Gel with Base Hydroxypropyl Methylcellulose and Poloxamer 188.

OBJECTIVE: The aim of this study was to determine the best formulation of ophthalmic in situ gel preparation by two different bases, Poloxamer 188 and HPMC (hydroxypropyl methylcellulose), with physical evaluation, such as organoleptic, pH, viscosity, and gel capacity during 28 days of storage time. MATERIALS AND METHODS: The two different concentrations of the gel made by using Poloxamer 188 were F1 (5%) and F2 (10%), and those made by using HPMC were F3 (0.45%) and F4 (1%). RESULTS: The results of this study showed that formulation 1 (F1) was the optimum formulation, having pH 6.45, viscosity of 5.47 cP, and a better gel capacity than other formulas. CONCLUSION: In situ gel for ophthalmic preparations is developed to mask the limitation of conventional forms of ophthalmic preparation. In situ gel technology significantly increase the effectivity of drugs in the raw material and drug bioavailability in new drug delivery systems based on in situ gel concept.