INTRODUCTION:

Gels derived from cellulose derivatives such as carboxymethyl cellulose (CMC) and hydroxypropyl methylcellulose (HPMC) are emerging carriers for drug delivery via oral as well as topical routes. Hydrophilic polymers are characterized by excellent biocompatibility, biodegradability, and tunable viscosity, thereby allowing controlled release and enhanced mucoadhesion¹. pH-responsive CMC-gelatin hydrogel systems manifested sustained and specific release of anticancer agents only under acidity along with confirmed in vivo safety and pharmacokinetics². Meanwhile, HPMC-based hydrogels are widely utilized due to their customizable rheology and ability to prolong drug residence time, making them suitable for a range of therapeutic applications³. This is revolutionizing my note of concern- if not argument- as a matter of fact with respect to the parameters and approach by which each formulation can possibly be exploited for maximum output in addition to characterization methods.

Natural cellulose, which can be purified from plants or bacteria, is a linear polymer of β-1,4-linked D-glucose units, and is very useful from an environmental viewpoint in terms of biocompatibility, biodegradability, and abundance⁴. Natural cellulose is obtained from plants, wood, cotton or bamboo, which gives cellulose moderate tensile strength and retains moisture at ~60%⁵. In contrast, bacterial cellulose (BC) has ultra-high purity and crystallinity, water-holding capacity (~100%), and a very fine and regular 3D nanofibrillar network⁵. These properties permit easy preparation of natural hydrogels through physical cross-linking with hydrogen bonds. Once these are processed into a nanocellulose form-cellulose nanocrystals (CNCs) and nanofibrils (CNFs)-it can now create injectable, self-healing hydrogels with tunable porosity and stimuli-responsive drug-release profiles⁶.

Oral gels are widely being used locally for conditions like ulcers, periodontitis, and fungal infections, while also being administered systemically in patients with swallowing difficulties. The formulation provides for mucoadhesion, controlled drug release, and ease of application. Besides cellulose-based systems, some other common polymers include chitosan, a natural cationic polymer known for its great mucoadhesive and antimicrobial properties, which can be very useful for periodontal and buccal drug delivery⁷. Alginate, obtained from brown seaweeds, forms ion-sensitive gels, permitting pH-dependent release which is particularly useful in gastroretentive formulations Pectin, another natural polymer, is used for the oral gels meant for colon targeting and swallowing aids. Carbopol (polyacrylic acid) is a synthetic polymer known for its high viscosity and sustained release abilities, generally used for oral treatments of ulcers⁸.

Tulsi (botanical name Ocimum tenuiflorum, also O. sanctum) is a sacred aromatic herb valued for its wide spectrum of medicinal properties. The essential oils are usually distilled by steaming, whereas polyphenolic and triterpenoid extracts are cold- or water-extracted. Common bioactives include eugenol, ursolic acid, rosmarinic acid, luteolin, and caryophyllene⁹. Well-known uses of Tulsi are in pharmaceutical preparations for anti-microbial, anti-inflammatory,antioxidant, and adaptogenic functions, such as oral tea, capsules, topical creams, and gels. In oral health, tulsi-based gels and pastes have been shown to treat gingivitis, periodontal disease, and oral submucous fibrosis, providing considerable relief from inflammation, bleeding, and burning sensations^10,11.

Hydrogels that are incorporated with carboxymethyl cellulose (CMC) and Tulsi extract are coming out to be effective local delivery systems for periodontal therapy. A formulation developed by Meenakshi et al. with CMC, sorbitol, and Tulsi extract under sink conditions produced a hydrogel with a greath swelling profile (≈11-16%) and sustained release for 20 days, reflecting excellent retention of the drug in the periodontal pockets for an extended duration^12,13. Ramamurthy and Bajpai Devika designed a hydrogel formulation that is characterized as CMC-Tulsi-sorbitol which would show not only the cytocompatibility (>85% cell viability) but also that it is a suitable non-toxic delivery vehicle¹⁴. On the other hand, Ramamurthy and Jayakumar's in situ HPMC–Carbopol gel with 2% Tulsi extract showed strong antioxidant (60–72%) and anti-inflammatory (76%) properties with low cytotoxicity thereby supporting its application in periodontal therapy¹⁵. Clinical evidence from Deepika et al. demonstrated that a 2% Tulsi gel significantly reduced edema and probing depths in periodontitis, comparable to tetracycline fibers over several months¹⁰.

Hence proper investigation of the prepared cellulose and dermal gels from cellulose and tulsi extract includes their physicochemical characterization such as FTIR, UV, HRSEM, drug release study, and invitro study. In addition, we study other aspects, such as those related to toxicology, antimicrobial, and antibacterial studies.

MATERIALS AND METHODS:

Materials:

All chemicals used in this study were of analytical grade. Distilled water (99.9% purity), hydrochloric acid (HCl), and sulfuric acid (H₂SO₄) were procured from Sigma-Aldrich, Chennai, Tamil Nadu, India (Pincode: 600113). Cellulose pulp was sourced from a local paper recycling facility located in the SIPCOT Industrial Area, Gummidipoondi (Pincode: 601201). Fresh Ocimum sanctum (Tulsi) leaves were collected from a certified herbal garden in Tambaram, Chennai (Pincode: 600045) and authenticated by a professional botanist. All water used for extraction and formulation was deionized and prepared using a double-distillation system in the laboratory.

Extraction of Cellulose:

Cellulose was extracted from recycled paper pulp using standard alkaline pulping methods. The pulp was treated with sodium hydroxide to remove lignin and hemicellulose, followed by sequential washing, bleaching, and neutralization. The purified cellulose was dried and ground for further use. For enhanced solubility and gelling properties, a portion of the extracted cellulose was chemically modified into carboxymethyl cellulose (CMC) via etherification. These cellulose derivatives are known for their mucoadhesive, thickening, and controlled drug release capabilities, making them suitable for pharmaceutical formulations.

Preparation of Ocimum sanctum Extract:

Fresh Tulsi leaves were washed thoroughly, shade-dried for 5–7 days, and ground into a fine powder. Ethanol (70%) was used for cold maceration of 50g of powdered leaves for 48–72hours with occasional stirring. The extract was filtered and concentrated using a rotary evaporator at 40–50 °C, then stored at 4°C until further use. The extract contains a range of active constituents including eugenol, ursolic acid, and rosmarinic acid, which are known for their antimicrobial, antioxidant, and anti-inflammatory properties¹⁶.

Formulation of Tulsi–Cellulose Gel:

The hydrogel formulation was prepared using the modified dispersion technique. CMC (2%w/v) was dissolved in deionized water and refrigerated for 24 hours to ensure full hydration. Sorbitol (0.5%w/v) and propylene glycol were added as plasticizers to enhance flexibility and moisture retention. Two milliliters of the concentrated Tulsi extract were incorporated into the hydrated CMC solution under continuous stirring¹⁷. This mixture was then added to a Carbopol-940 dispersion and neutralized using triethanolamine to achieve a physiological pH of 6.0–6.5. The final formulation was stored in sterile containers for further analysis¹⁸.

Physicochemical Characterization:

Comprehensive characterization of the Tulsi–cellulose gel was conducted using FTIR, UV-Visible spectroscopy, and high-resolution scanning electron microscopy (HRSEM): FTIR (Fourier Transform Infrared Spectroscopy): Conducted in the range of 4000–400cm⁻¹ using the KBr pellet method to confirm the interaction between Tulsi phytoconstituents and the cellulose matrix. UV–Visible Spectroscopy: Recorded between 200 and 400nm to confirm the presence of eugenol and other bioactives, with a peak absorbance observed at 298nm. HRSEM: Used to observe the surface morphology of the gel. Samples were gold-coated and analyzed at an accelerating voltage of 10–15 kV. A porous, interconnected network was identified, which supports efficient drug loading and sustained release.

In Vitro Drug Release Study:

Drug release behavior of the Tulsi-loaded cellulose gel was evaluated using a Franz diffusion cell setup with a dialysis membrane. The receptor compartment was filled with phosphate buffer (pH 6.8) and maintained at 37±0.5°C to simulate oral conditions. At predetermined intervals, aliquots were withdrawn and analyzed using UV–Visible spectroscopy at 298 nm to quantify eugenol release. The formulation exhibited an initial burst release in the first 2hours, followed by sustained drug release for up to 24hours, indicative of a biphasic kinetic profile suitable for prolonged therapeutic action.

Antimicrobial Evaluation:

The antibacterial efficacy was tested using the agar well diffusion method against Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans. Plates were incubated at 37°C for 24hours and zones of inhibition were measured. The results showed notable antimicrobial activity, comparable to that of standard antibiotics like chlorhexidine. The activity is attributed to the presence of eugenol and ursolic acid, known to disrupt microbial cell membranes and inhibit bacterial proliferation.

Statistical Analysis:

All experiments were conducted in triplicate. Data are presented as mean±standard deviation. Drug release kinetics were analyzed using mathematical models including zero-order, first-order, and Higuchi models to determine the best-fit release mechanism.

RESULTS AND DISCUSSION:

FTIR Analysis:

The Fig.1 signifies the FTIR spectrum of extracted cellulose exhibited distinct peaks confirming its structural integrity. A broad absorption band at ~3340 cm⁻¹ was attributed to O–H stretching vibrations, indicating the presence of inter- and intramolecular hydrogen bonding. Peaks at 2895 cm⁻¹ and 1427 cm⁻¹ corresponded to C–H stretching and CH₂ bending, respectively, while the band at 1058 cm⁻¹ confirmed C–O–C stretching within β-1,4-glycosidic bonds, validating the cellulose backbone. No contaminant peaks were observed, suggesting high purity¹⁹.

Tulsi extract demonstrated characteristic peaks at ~3400 cm⁻¹ (O–H), 2920–2850 cm⁻¹ (C–H), 1600 cm⁻¹ (C=C), and 1020–1250 cm⁻¹ (C–O), confirming the presence of bioactive compounds such as eugenol, flavonoids, and terpenoids. The FTIR spectrum of the final Tulsi-loaded cellulose gel retained key functional group peaks with minor shifts and reduced intensity²⁰, indicating successful physical encapsulation without chemical degradation or incompatibility²¹. These subtle spectral shifts imply hydrogen bonding between cellulose and Tulsi phytoconstituents, affirming the stability of the formulation²², where previously indicated reports indicate the role of appropriate excipients in the integrity of formulations and their subsequent release profiles²³.

Fig.1 Spectrum of extracted cellulose

HRSEM Morphology:

HRSEM analysis of Fig.2 revealed a uniform, porous gel structure with pore sizes ranging between 10 and 50 µm²⁴. The surface morphology was smooth and devoid of phase separation or crystalline residue, indicating homogeneous distribution of the Tulsi extract within the cellulose matrix²⁵. The porous and hydrophilic structure supports efficient drug loading and sustained release²⁶. Increased surface area and stable entrapment facilitate enhanced mucoadhesive interaction, making the formulation ideal for oral topical drug delivery applications²⁷.

Fig.2 - HRSEM analysis of gel structure

In Vitro Evaluation:

The in vitro drug release profile of Fig.3, studied using a Franz diffusion cell, exhibited a biphasic pattern. An initial burst release of ~40% was observed within the first 10 hours, followed by a gradual, sustained release reaching ~90–95% by 30 hours. In contrast, pure Tulsi extract and Adriamycin demonstrated rapid and less controlled release profiles. This controlled release behavior highlights the ability of the cellulose matrix to modulate diffusion and prolong drug availability, essential for extended oral mucosal application and reduced dosing frequency²⁸.

Fig. 3: Invitro analysis using Franz diffusion cell

Antimicrobial Activity:

The well diffusion assay indicated that Tulsi-cellulose gel exhibited antimicrobial activity against Staphylococcus aureus and E. coli, with inhibition zones measuring 11mm, 17.45mm, and 25.67mm, respectively²⁹. They were found to be comparable to chlorhexidine gel, a standardized oral antimicrobial. Disruption of bacterial membrane and metabolic activity has been attributed to Eugenol and ursolic acid, the most bioactive compounds of Tulsi²⁹. Since both support the antibacterial efficacy, it could also serve in controlling dental plaque and periodontal pathogens³⁰. This indeed makes the Tulsi-cellulose gel a new herbal alternative to oral hygiene and periodontal therapy³¹.

Table. 1 Antimicrobial properties of Adriamycin, Ocimum tenuiflorum, Oral/dermal- based gel

Samples	Zone of inhibition (mm)
Samples	*E.coli*	*S.aureus*
Adriamycin	12.08+0.22	10.52+0.22*
Ocimum tenuiflorum	17.45+0.52*	16.66+0.31
Oral/dermal- based gel	25.67+0.72	26.35+0.52*

Drug Release Study:

UV–Visible spectrophotometry at 298nm confirmed eugenol as the primary released component. The gel demonstrated a two-phase release: an initial burst of 59% within 12 hours, followed by sustained release reaching 86% over 48hours shown in Fig.4. The cellulose matrix contributed to the formulation’s swelling and mucoadhesive properties, enabling prolonged retention in the oral cavity. The gel remained chemically stable throughout the study duration, with no degradation of active compounds. These findings support the suitability of the Tulsi–cellulose gel for localized, sustained oral drug delivery³³, and sustained release tablet formulations³⁴.

Fig. 4 Drug Release Study

Recent advances show that gelatin-based scaffolds, especially when combined with collagen or hydroxyapatite, enhance regeneration³⁵. Electrospun composites aid wound healing³⁶, exhibit hemostatic effects³⁷, and influence cytokine expression critical to tissue remodeling³⁸.

CONCLUSION:

This study successfully formulated and characterized a cellulose-based hydrogel incorporating Ocimum sanctum (Tulsi) extract for oral and dermal drug delivery. The cellulose, extracted from recycled paper, demonstrated excellent mucoadhesive strength (28.5± 1.2g/cm²) and suitable viscosity (2,300±50cP) for mucosal application. FTIR confirmed functional group integrity with characteristic O–H and C–H stretches, indicative of eugenol presence. HRSEM analysis revealed a porous gel matrix with pore diameters of 10–50µm, promoting sustained drug release. The in vitro drug release profile exhibited a biphasic pattern: an initial burst of ~40% release within 10h, followed by a prolonged release reaching 90–95% over 30hours, aligning with the Higuchi model (R²>0.98). The gel maintained a physiologically relevant pH of 6.8±0.2, suitable for oral applications. Antimicrobial assays showed significant activity, with inhibition zones measuring 17.45mm against E. coli and 25.67mm against S. aureus, comparable to commercial chlorhexidine formulations. These quantitative results confirm that the Tulsi–cellulose hydrogel is a potent, biocompatible, and eco-friendly drug delivery system. Its sustained release kinetics, effective antimicrobial properties, and favorable physical characteristics support its potential as a natural therapeutic for oral mucosal infections. Future studies should explore in vivo bioavailability and clinical efficacy to validate its translational utility in oral care.

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Received on 18.06.2025 Revised on 13.10.2025

Accepted on 17.12.2025 Published on 01.07.2026

Available online from July 04, 2026

Research J. Pharmacy and Technology. 2026;19(7):3121-3126.

DOI: 10.52711/0974-360X.2026.00443

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.