Intranasal Delivery of Carvedilol- and Quercetin-Encapsulated Cationic Nanoliposomes for Cardiovascular Targeting: Formulation and In Vitro and Ex Vivo Studies.

Carvedilol (CVD), an adrenoreceptor blocker, is a hydrophobic Biopharmaceutics Classification System class II drug with poor oral bioavailability due to which frequent dosing is essential to attain pharmacological effects. Quercetin (QC), a polyphenolic compound, is a potent natural antioxidant, but its oral dosing is restricted due to poor aqueous solubility and low oral bioavailability. To overcome the common limitations of both drugs and to attain synergistic cardioprotective effects, we formulated CVD- and QC-encapsulated cationic nanoliposomes (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. We designed CVD- and QC-loaded cationic nanoliposomal (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. In vitro drug release studies of CVD/QC-L.O.F. (16.25%) exhibited 18.78 ± 0.57% of QC release and 91.38 ± 0.93% of CVD release for 120 h. Ex vivo nasal permeation studies of CVD/QC-L.O.F. demonstrated better permeation of QC (within 96 h), i.e., 75.09% compared to in vitro drug release, whereas CVD permeates within 48 h, indicating the better interaction between cationic NLPs and the negatively charged biological membrane. The developed nasal gel showed a sufficient mucoadhesive property, good spreadability, higher firmness, consistency, and cohesiveness, indicating suitability for membrane application and intranasal administration. CVD-NLPs, QC-NLPs, and CVD/QC-NLPs were evaluated for in vitro cytotoxicity, in vitro ROS-induced cell viability assessment, and a cellular uptake study using H9c2 rat cardiomyocytes. The highest in vitro cellular uptake of CVD/QC-cationic NLPs by H9c2 cells implies the benefit of QC loading within the CVD nanoliposomal carrier system and gives evidence for better interaction of NLPs carrying positive charges with the negatively charged biological cells. The in vitro H2O2-induced oxidative stress cell viability assessment of H9c2 cells established the intracellular antioxidant activity and cardioprotective effect of CVD/QC-cationic NLPs with low cytotoxicity. These findings suggest the potential of cationic NLPs as a suitable drug delivery carrier for CVD and QC combination for the intranasal route in the treatment of various cardiovascular diseases like hypertension, angina pectoris, etc. and for treating neurodegenerative disorders.

Effect of dry heat and its combination with vacuum heat on physicochemical, rheological and release characteristics of Alocasia macrorrhizos retrograded starches.

Retrograded starches have received increasing attention due to their potential excipient properties in pharmaceutical formulations. However, to evade its application-oriented challenges, modification of retrograded starch is required. The study emphasizes influence of dry heating and the dual heat treatment by dry heating amalgamation with the vacuum heat treatment on quality parameters of retrograded starch. The starch was isolated by using two different extraction media (0.05 % w/v NaOH and 0.03 % citric acid) from Alocasia macrorrhizos and then retrograded separately. Further, retrograded starches were first modified by dry heating and afterwards modified with combination of dry and vacuum heating. Modification decreased moisture, ash content and increased solubility. Modified Samples from NaOH media had higher water holding capacity and amylose content. X-ray diffraction revealed type A and B crystals with increasing crystallinity of retrograded heat-modified samples from NaOH media. Thermogravimetric analysis, differential scanning calorimetry confirmed thermal stability. Shear tests showed shear-thinning behavior whereas dominant storage modulus (G/) over loss modulus (G//), depicting gel-like behavior. Storage, loss, and complex viscosity initially increased, then decreased with temperature. In-vitro release reflects, modified retrograded starches offers versatile drug release profiles, from controlled to rapid. Tailoring starch properties enables precise drug delivery, enhancing pharmaceutical formulation flexibility and efficacy.

Evaluating the effects of time-dependent drying and pressure heat treatments on the variation of physicochemical and rheological properties of suran starch.

Recent research developments have shed light on hydrothermal treatment as a commonly employed method for physical modifications. Surprisingly, there is a scarcity of studies investigating the impact of time variation which is a critical process parameter. Therefore, it is important to closely monitor the critical process parameters throughout the process. Hence, the present study investigates the influence of time-dependent hydrothermal modifications like dry heat (DH) and pressure heat (AT) on Suran starch, focusing on the physicochemical and rheological properties. Over time, the modified starches showed increased swelling and solubility power due to intermolecular hydrogen bond disruption. Prolonged heat exposure made starch granules more susceptible to water absorption, enhancing their swelling capacity. Rheological analysis revealed time-dependent shear-thinning behaviour, with modified starches showing improved resistance to shear stress compared to native starch. Extended heat treatment led to structural rearrangements in starch granules, resulting in increased entanglement and higher viscosity, contributing to improved mechanical properties. Interestingly, the AT-25 starch sample exhibited the highest elasticity, indicating enhanced structural rigidity under high shear conditions. The time-dependent alterations due to pressure treatments improved the functionalities and structural integrity of modified Suran starch. These findings highlight the positive impact of time-dependent heat treatment modifications on Suran starch, making it a valuable resource for various industrial applications. Enhancing the industrial viability of underutilized Suran starch could contribute significantly to meeting the demand for starch in various industries.

Phytochemical Profiling and Pharmacological Evaluation of Leaf Extracts of Ruellia tuberosa L.: An In Vitro and In Silico Approach.

The present study was designed to appraise the photoprotective, antioxidant, and antibacterial bioactivities of Ruellia tuberosa leaves extracts (RtPE, RtChl, RtEA, RtAc, RtMe, and RtHMe). The results showed that, RtHMe extracts of R. tuberosa was rich in total phenolic content, i. e., 1.60 mgGAE/g dry extract, while highest total flavonoid content was found in RtAc extract, i. e., 0.40 mgQE/g. RtMe showed effective antioxidant activity (%RSA: 58.16) at the concentration of 120 µL. RtMe, RtEA and RtHMe exhibited effective in vitro antibacterial activity against Gram-negative bacteria (E. coli). In silico docking studies revealed that paucifloside (-11.743 kcal/mol), indole-3-carboxaldehyde (-7.519 kcal/mol), nuomioside (-7.275 kcal/mol), isocassifolioside (-6.992 kcal/mol) showed best docking score against PDB ID 2EX8 [penicillin binding protein 4 (dacB) from Escherichia coli, complexed with penicillin-G], PDB ID 6CQA (E. coli dihydrofolate reductase protein complexed with inhibitor AMPQD), PDB ID 2Y2I [Penicillin-binding protein 1B in complex with an alkyl boronate (ZA3)] and PDB ID 2OLV (from S. aureus), respectively. Docked phytochemicals also showed good drug likeness properties.

Effect of pressure treatment duration on the rheological characteristics of dry-heated alocasia starch in the presence of monosaccharide and disaccharide.

The current work investigated the impact of different pressure processing times (5, 10, and 15 min) at 120 psi on the rheological behavior of a mixture of dry-heated Alocasia macrorrizhos starch with monosaccharide and disaccharide. Shear-thinning behavior was exhibited by the samples in steady shear evaluation and the highest viscosity was observed in the 15 min pressure treated samples. In the initial phase of amplitude sweep measurement, samples exhibited strain dependency but later they remain unaffected with applied deformation. The greater value of Storage modulus (G') than loss modulus (G″) (G' > G″) indicating the weak gel-like behavior. Increasing in pressure treatment duration enhanced the value of G' and G″ with applied frequency and found maximum at 15 min. In temperature sweep measurement the G', G″ as well as complex viscosity curves increased initially and then decreased after achieving peak temperature. However, the rheological parameters of the samples treated under long pressure processing time were found to be improved during temperature sweep measurements. The resulting extremely viscous, pressure-treated dry-heated Alocasia macrorrizhos starch-saccharides combination has a variety of uses in different pharmaceuticals as well as in food industries.

Structure and drug delivery relationship of acidic polysaccharides: A review.

Scientists from across the world are being inspired by recent development in polysaccharides and their use in medical administration. Due to their extraordinary physical, chemical, and biological characteristics, polysaccharides are excellent materials for use in medicine. Acidic polysaccharides, which include Pectin, Xanthan gum, Carrageenan, Alginate, and Glycosaminoglycan, are natural polymers with carboxyl groups that are being researched for their potential as drug delivery systems. Most publications do not discuss how the different polysaccharides interact structurally in terms of drug delivery, which limits the scope of their use. The purpose of this review is to inform readers about the structural activity correlations between acidic polysaccharides, their different modification process and effects of combination of various acidic polysaccharides which have been used in drug delivery systems and expanding their potential applications, and bringing new perspectives to the fore.

Influence of disaccharide and monosaccharide on the rheological behavior of dry-heated alocasia starch under high pressure assisted treatment.

High viscous products made with starch are of great scientific interest in the food, pharmaceutical, and cosmetic industries because they can be used to make creams and gels, as well as functional foods and nutritional products. But, obtaining a good quality highly viscous materials represent a technological challenge. In this present study, the effect of high-pressure treatment at 120 psi for different time interval on the mixture of dry-heated alocasia starch in presence of monosaccharide and disaccharide was studied. A flow measurement test on the samples revealed their shear-thinning behavior. With 15 min of high-pressure processing time, the dry-heated starch and saccharide mixtures displayed the highest viscosity. The dynamic viscoelasticity measurement showed that the storage and loss modulus was enhanced significantly after high-pressure treatment, and all pressure-treated samples showed a gel-like structure (G/>G//). In temperature sweep measurement, the rheological profile of storage modulus, loss modulus, and complex viscosity exhibited a two-stage pattern, i.e., first increased, then decreased, and their values were enhanced significantly after pressure treatment. The resultant highly viscous dry-heated starch and saccharide system have various functionalities in diverse food and pharmaceutical products.

Structural insight into a glucomannan-type extracellular polysaccharide produced by a marine Bacillus altitudinis SORB11 from Southern Ocean.

Extracellular polysaccharide (EPS) produced by a deep-sea, psychrotolerant Bacillus altitudinis SORB11 was evaluated by considering physiochemical nature and structural constituents. The productivity of crude EPS was measured ~ 13.17 g L-1. The surface topography of the crude EPS showed a porous, webbed structure along with a branched coil-like configuration. The crystalline crude EPS contained a high amount of sulfur. Further, the crude EPS was subjected for purification. The molecular weight of purified EPS was determined ~ 9.8 × 104 Da. The purified EPS was appeared to show glucomannan-like configuration that is composed of → 4)-ß-Manp-(1 → and → 4)-ß-Glcp-(1 → residues. So, this polysaccharide was comparable to the structure of plant-derived glucomannan. Subsequently, EPS biosynthesis protein clusters like EpsC, EpsD, EpsE, and glycosyltransferase family proteins were predicted from the genome of strain SORB11, which may provide an insight into the production of glucomannan-type of polysaccharide. This low molecular weight linear form of glucomannan-type EPS might be involved to form a network-like unattached aggregation, and helps in cell-to-cell interaction in deep-sea microbial species.

Enhancing delayed release characteristics of chapparada avare seed starch.

This study aims to evaluate the effects of pregelatinization in improving delayed release characteristics of native chapparada avare starch. Physicochemical properties and drug release characteristics were evaluated for the native and pregelatinized starches using established methods. The moisture content decreased from 12.13 ± 0.15% to 8.73 ± 0.12%, whereas amylose content (6.91 ± 0.06-21.13 ± 0.03), swelling power and water holding capacity (211.04 ± 0.03-513.03 ± 0.03) showed steady rise with pregelatinization time. The result of X ray diffraction pattern for pregelatinized starch, showed absence of 18.4° and 23.2° 2θ peaks thereby indicating reducing crystallinity, compared to native starch, whereas FESEM micrograph showed complete disruption of granular structure due to pregelatinization of native starch. The in vitro dissolution studies conducted in gastric and intestinal pH showed that tablets prepared with both native (NPL) and modified starch (PG15, PG20, PG 25), are gastro protective with less than 25% drug release in pH 1.2. In pH 6.8, PG 20 and PG 25 showed optimum drug release of 21.23 ± 0.54% and 19.40 ± 0.48% respectively in 6 h compared to 42.52 ± 0.21% release of NPL formulation, thereby indicating time based delayed drug release characteristics of over its native counterpart.

Studies to predict the effect of pregelatinization on excipient property of maize and potato starch blends.

This study focuses on the effect of co-processing on physicochemical and drug release properties of starch mixtures. Different mixtures of native maize and potato starch were pregelatinized for different time intervals. The pregelatinized starch mixture was observed to have higher amylose content than that of native starches. The flow properties of starch mixtures were found to improve after pregelatinization. FTIR and XRD showed changes in structure and crystallinity of native starch due to pregelatinization. The FESEM images showed complete disruption of granular structure of native starch. Native starch was found to be more viscous than pregelatinized starch and all starch samples exhibited Non-Newtonian shear thinning behaviour. The tablets prepared from native starch showed rapid release of drug compared to the modified starches, and increase in the amount of potato starch resulted in sustained drug release. This indicates the utility of pregelatinized starch mixtures with high proportion of potato starch in sustained drug delivery systems.

Impact on stabilization of ionic gum emulsions by natural and thermally modified Chironji gum.

Ionic gums like acacia and tragacanth are known for their emulsifying properties but lower viscosity limits its use. This study explores the effects of natural chironji gum and its thermally modified form on the emulsifying properties of acacia and tragacanth. Formulations of chironji gum (CG) O/W emulsion FA1-FA4 were prepared with acacia and FT1-FT4 with tragacanth respectively. Heat treated gums(CGTs) were obtained by heating CG at 110 °C for time intervals 24 h, 48 h and 96 h. Similarly formulations FHA1-FHA12 and FHT1-FHT12 were prepared with acacia and tragacanth replacing CG with heat treated gums. Heat treated gum formulations showed better stabilizing properties than natural CG emulsions. The FA1-FA4 and FT1-FT4 formulations had droplet size in the range of 9.77-26.55 µm and zeta potential ranging from -14.8 mV to -23.2 mV. In contrast, the droplet size and zeta potential of FHA1-FHA12 and FHT1-FHT12 were in range of 1.42-17.5 µm and -17.2 mV to -40.6 mV respectively signifying improved stabilizing capacity of CGT gums. The droplet size and zeta potential of these formulations remained stable even after 7 days of storage at room temperature with no visible phase separation of the formulation observed for more than a month.

A Review on Nutritional and Biological Potential of Earthstar Mushrooms, Species of Genus Astraeus ( Agaricomycetes).

The Astraeus genus (Diplocystaceae) of ectomycorrhizal edible mushrooms is represented by nine species: A. asiaticus, A. hygrometricus, A. koreanus, A. morganii, A. odoratus, A. pteridis, A. sirindhorniae, A. smithii, and A. telleriae. Astraeus mushrooms, because of their characteristic delicacy and aroma, are marketed in several countries. Chemical examinations of these mushrooms have revealed their nutritional properties and bioactive constituents. Here, the proximate nutritional composition of A. hygrometricus and A. odoratus, and chemistry and biological activity of A. asiaticus, A. hygrometricus, A. odoratus, and A. pteridis were reviewed. Several mycochemicals, including polysaccharides, terpenoids, steroids, phenolics and heterocyclic compounds, have been characterized in their fruiting body. Various biological activities of these compounds are also discussed.

Effect of thermal modification on the release characteristics of pink potato starch of Jharkhand, India.

Excipient plays an essential role in drug delivery system, which promotes the drug to reach a particular site of action. Excipients directly or indirectly affect the duration and rate of drug release and absorption. In the current study, physicochemical properties, flow properties and release characteristics of native and modified pink potato starches were investigated to determine their excipient characteristics. Amylose content, water holding capacity, swelling and solubility properties were found to increase after pregelatinization and retrogradation. The SEM micrographs reveals the loss of granular structure of native after thermal modification. The FT-IR study confirms the gelatinization characteristics of the pregelatinized starch. X-ray diffraction pattern confirms the reduction of crystallinity after thermal modification. Tablets containing Paracetamol as a model drug showed that native, pregelatinized and modified pink potato starch could be useful for the manufacturing of immediate release formulation.

Effect of dry heating and ionic gum on the physicochemical and release properties of starch from Dioscorea.

To meet the ever increasing industrial demand for excipients with desirable properties, modified starch is regarded as an alternative to it. With this in mind, the present study focuses on the modification of starches of Dioscorea from Jharkhand (India) using dry heat treatment with and without ionic gum. Modified starches were prepared using sodium alginate (1% w/w). Native and modified starches were subjected to heat treatment at 130°C for 2h and 4h. The effect of heating and ionic gum on the properties of Dioscorea starch was investigated. The amylose content, water holding capacity, micromeritic properties, swelling power, solubility and morphology of starches were evaluated. Dry heat treatment of starches without gum showed an increment in water-holding capacity after two-hours heating, but no such increment was found after four-hours heating. Oil binding capacity of starches modified with gum varied from 62% to 78%. Strongest effect of heat treatment occurred on the morphology of starches and thereby modified starches showed distorted surface morphology. Amylose content (21.09-21.89%) found to be decreased with the addition of gum which lead to decrease in paste clarity. Starches heated with gum at high-temperature resulted in restrict swelling and slight increase in solubility. Micromeritic properties of the modified starches showed the good flow properties. Further, the modified starches were investigated for in-vitro release studies and that the thermally modified derivatives can be a good prospect in slow release formulations.

Homogeneous carboxymethylated orange pulp cellulose: Characterization and evaluation in terms of drug delivery.

The aim of the present study is to develop an environment-friendly method to convert orange pulp wastes to Carboxymethyl cellulose (CMC) by homogeneous substitution. Carboxymethylation of Orange pulp treated with alkaline PEG solutions was investigated and characterized by means of TGA, DSC, XRD and SEM and compared with commercial CMC. The TGA data reveals that shifting of peaks was observed towards lower temperature with increase in monochloroacetic acid (MCA). SEM studies showed greater blending of particulate powder with increasing MCA content. The crystallinity of synthesized CMC was found to be lower than the commercial CMC. Finally, the cellulosic materials were evaluated for the formulation and dissolution studies of prepared tablets. Dissolution release studies shows that synthesized cellulose (CMCOP5, CMCOP8, CMCOP11) release up to 70.1±0.04%, whereas the commercial CMC 78.184±0.07% in 8h respectively and thereby suggests that it may be used in delayed drug delivery and targeting drugs to the colon. The synthesized CMC from orange pulp may be used as substitute for the commercial CMC.

Effect of carboxymethylation on physicochemical, micromeritics and release characteristics of Kyllinga nemoralis starch.

Lesser usages of native starch has attracted attention in the modification of starch to incorporate its benefits for pharmaceutical application. A work has been carried out to study the influence of carboxymethylation on the morphological, physico-chemical, powder, spectroscopical and drug discharge characteristics of native starch. Various amount of monochloroacetic acid was used to study the influence of degree of substitution (DS) on the diverse characteristics of modified starch. Amylose content was found to be reduced with the increase in degree of substitution. An enhanced degree of structure deformation was observed with the increment in the DS by the help of scanning electron micrographs. The FT-IR spectra established the polysaccharide nature and the carboxymethylation of the chemically modified starch molecules through the new bands at 1602cm-1, and 1418.69cm-1. The stability of carboxymethyl starches pertaining to the temperature has been revealed by thermogravimetric analysis. Micromeritics of carboxymethylated starches shows their effectiveness as excipients in tablet formulation. The delayed % release of the drug, with the rise in degree of substitution from the tablets prepared marks that the carboxymethyl derivatives of Kyllinga nemoralis rhizomes starch may be used as a suitable source of excipient for sustained release formulations.

Studies on water soluble polysaccharides from Pithecellobium dulce (Roxb.) Benth. seeds.

In this existing experimental work, water soluble PDP polysaccharides were secluded from Pithecellobium dulce (Roxb.) Benth. seeds. The physicochemical properties were analyzed in terms of swelling power, solubility, pH and water holding capacity. Micromeretic studies proved the polysaccharide may be used a potential pharmaceutical adjuvant. The polysaccharide was characterized by FT-IR, SEM, TGA and NMR techniques. Methylation analysis confirmed that the polysaccharide is composed of Arabinose (Araf) units. The chemical shifts of anomeric proton region were found in the region of 4.4-5.5ppm. Thermogravimetric analysis showed that PDP polysaccharide was thermally stable. The in vitro antioxidant capacities of the polysaccharide were investigated in terms of scavenging of hydroxyl radicals, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals, hydrogen peroxide (H2O2) and reducing power assay. The polysaccharide fractions showed activity in a concentration dependent manner which was comparable to the standard, ascorbic acid.

Physicochemical properties and release characteristics of starches from seeds of Indian Shahi Litchi.

Many conventional sources of starches are from staple foods. Non-conventional and cheap sources of starch are being explored. Starch was isolated from Shahi Litchi seeds using two extraction media; acidic (citric acid 0.3%, w/w; LC) and alkaline (NaOH 0.5%, w/w; LN). Each starch was investigated for various properties such as structural, morphological and functional. The percentage yield of LN and LC was 11% and 12.6%, respectively. Morphological properties of both starches show same structural makeup, but compound granules were in LN starch. Moisture content, amylose content was found to be higher LC starch than in LN starch, which indicates that extraction media affects the properties of starch. FTIR confirmed the carbohydrate nature of the both isolated starches. TGA data of both starches reveal slight difference in stability with temperature. In vitro release of both starches shows the release up to 58.95±0.04% and 67.184±0.07% in 5h for LN and LC, respectively, that indicates that these starches can be used in delayed drug delivery and targeting drugs to the colon.

Effect of carboxymethylation on physicochemical and release characteristics of Indian Palo starch.

Limited application of native starch has created the interest in the modification of starch to extend its asset for pharmaceutical application. An effort has been made to study the influence of carboxymethylation on morphological, physicochemical and drug release properties of wild Indian Palo (Curcuma angustifolia) starch. Carboxymethyl starches of different degree of substitution (0.046-0.256) were prepared using varying amount of monochloroacetic acid. The characteristic peaks at around 1600cm(-1) confirmed the carboxymethylation of starch. Morphological studies showed that porous structure formed on the surface of the starch granules and degree of deformity was found to be increased with the increment in the degree of substitution. Amylose content was decreased with the increase in degree of substitution. The TGA data showed that the carboxymethyl starches were thermally stable. Swelling and solubility power was found to be improved with the increase in the temperature. Micromeritic properties of carboxymethyl starches proved its usefulness as excipients in tablet manufacturing. Release profile of paracetamol was found to be decreased with the increase in the degree of substitution, and this proves the suitability of carboxymethyl Indian Palo starch in sustained-release tablets.

Physicochemical and tablet properties of Cyperus alulatus rhizomes starch granules.

The starch extracted from rhizomes of Cyperus alulatus (CA) was characterized for its physicochemical, morphological and tableting properties. Rhizomes of CA yield a significant quantity of starch granules (CASG) i.e., 11.93%. CASG was characterized in terms of moisture, ash and amylose contents, solubility and swelling power, paste clarity and water retention capacity. The swelling power was found to be significantly improved with the increase in temperature. Scanning electron micrographs revealed that the granule's surface was smooth, the granules were spherical, mostly round, disc like, and the size range was 6.65-12.13 µm. Finger print region in FTIR spectra confirmed its carbohydrate nature. The evaluated micromeritic properties of extracted granule's bulk density, tapped density, Carr's index, Hausner ratio, true density and porosity render unique practicability of CASG being used as an adjuvant in pharmaceutical solid dosage forms. Tablets prepared by using CASG showed higher mechanical strength and more disintegration time, which depicted the characteristic binding nature of the starch granules. As CASG is imparting better binding properties in less concentration and also it can be used in combination with the established starches to get the synergistic effect; this starch can be used commercially in the tablet preparation.