INTRODUCTION:

Tropical drug delivery is a preferred approach to treat dermatological disorders. However, the skin's outermost layer, the stratum corneum, presents a significant challenge by acting as a barrier to drugs. To overcome this, researchers have turned to lipid-based colloidal carriers, like liposomes and microsponges, to facilitate drug delivery. Microsponges, in particular, have gained popularity for their unique properties, including their ability to adhere to the skin, improve hydration, and exchange lipids with the epidermis. These characteristics make them an ideal option for delivering drugs to the skin while overcoming the barrier presented by the stratum corneum.^1,2,3

Microsponges are a type of drug delivery system that has been widely used in the pharmaceutical industry for the past few decades. In recent years, they have also gained attention in the field of skincare, where they have been shown to improve the delivery and efficacy of active ingredients in topical formulations. Microsponges are small, porous particles made of cross-linked polymers, such as polyurethane or polyacrylate. These particles are capable of absorbing and releasing a variety of substances, including drugs, vitamins, and other active ingredients.^4,5

When used in skincare products, microsponges can help to enhance the penetration of active ingredients into the skin, reduce irritation, and increase the stability and shelf life of formulations. They can also provide sustained release of active ingredients over time, which can improve their efficacy.^6,7

One of the most promising applications of microsponges in skincare is in the treatment of acne. Studies have shown that microsponge-based formulations can deliver acne-fighting ingredients directly to the affected area, resulting in a reduction in acne lesions and an improvement in skin texture. Microsponges have also been used in anti-aging products to deliver ingredients that promote collagen production and improve skin texture. In addition, they have been used to deliver sunscreens and other UV-blocking agents, which can protect the skin from damage caused by UV radiation.

Advantages of microsponges:

Microsponges are a type of delivery system that consist of tiny porous particles, usually made of polymers, that can absorb and release active ingredients. Here are some advantages of microsponges:

1. Controlled release of active ingredients:

Microsponges can release active ingredients in a controlled manner, which means they can provide sustained release of a drug over a longer period of time. By reducing the frequency of dosing and lowering side effects, this can increase the drug's effectiveness and safety.¹²

2. Protection of active ingredients:

Microsponges can protect active ingredients from degradation, oxidation, or other chemical reactions that can reduce their potency. This can improve the stability of the drug and increase its shelf-life.⁹

3. Improved bioavailability:

Microsponges can improve the bioavailability of poorly soluble drugsby increasing their solubility and absorption in the body. This can enhance the therapeutic effect of the drug and reduce the required dosage.⁸

4. Targeted delivery:

Microsponges can be engineered to target specific areas of the body, such as the skin, mucosa, or lungs, by adjusting their size, shape, and surface properties. This can improve the local delivery of drugs and reduce systemic exposure.¹²

5. Versatility:

Microsponges can be employed with a variety of active compounds, such as drugs, cosmetics, and nutrition. They can also be formulated into various dosage forms, such as creams, gels, and foams, for different applications.¹¹

6. Ease of formulation:

Microsponges are easy to formulate and can be prepared using simple and cost-effective methods.⁸

7. Enhanced drug penetration:Microsponges can adhere to the skin and enhance drug penetration to different skin layers, including the epidermis and dermis.¹⁰

8. Reduced systemic toxicity:Microsponges can reduce systemic toxicity by restricting the therapeutic effect to the affected area of the skin and minimizing systemic absorption.¹⁰

Benefits of microsponges over other formulations:

Microsponges offer sustained drug release, stability, high payload capacity, and versatility, making them advantageous for topical formulations.

Benefits over conventional formulations:

Conventional topical drug formulations target the outer layers of the skin, releasing their active ingredients upon application and resulting in the rapid absorption of concentrated ingredients. This can lead to excessive accumulation in the epidermis and dermis, causing side effects such as irritation. Microsponge systems can minimize such side effects while maintaining efficacy by delivering the active ingredient gradually to the skin. For example, microsponge loaded Benzoyl peroxide formulations, have shown excellent efficacy in treating skin conditions like acne while minimizing irritation.¹³

Benefits over microencapsulation and liposomes:

While microcapsules can regulate the release rate of the API, the drawback is the entire API is released when the wall ruptures. Liposomes are effective transporters, but stability issues and the need for preservatives can limit their efficacy. Microsponges are stable across a wider pH range and at high temperatures. They also have a higher entrapment effectiveness and do not require preservatives, making them an economically feasible and microbiologically stable option for drug delivery systems.^14,15,16

Benefits over ointments:

The utilization of ointments for drug delivery is often limited by poor patient compliance as a result of their unappealing appearance, thick and oily texture, and low efficiency as drug delivery systems. This can cause irritation and sensitization due to the need for high concentrations of active ingredients. Moreover, topical formulations may possess unpleasant odors, uncontrolled evaporation of the active ingredient, and potential incompatibility of drugs with the vehicle. Nevertheless, the microsponge system can address these concerns by prolonging the active ingredient's residence time on the skin surface, thereby enhancing its effectiveness.^14,15

Drug release mechanism:^17,18

Microsponge technology allows for controlled release of active ingredients in response to external triggers such as temperature, pressure, solubility, and pH. These triggers use to adjust the release rate and optimize drug delivery for various applications.

Temperature Change:

At room temperature, some of the ingredients may be too thick to be released, but as the skin temperature increases, the flow rate of the ingredients also increases, leading to enhanced release. Therefore, temperature change can be used as an external trigger to control the release of active ingredients from microsponges

Pressure:

Rubbing or pressure applied on the skin can cause the microsponges to break and release the active ingredients onto the skin. This mechanism is particularly useful in topical formulations, where the act of rubbing the formulation onto the skin can help in the release of the active ingredients from the microsponges. The amount of pressure or rubbing required to trigger the release can be controlled by adjusting the properties of the microsponges, such as their size, porosity, and strength.

Solubility:

The release of water-soluble active ingredients from microsponges can be triggered in the environment contain water (like antiseptics and antiperspirants). This release can occur through diffusion and is dependent on the partition coefficient of the ingredient between the microsponges and the external environment.

pH Triggered Systems:

Varying the coating on microsponges release active ingredient whichenable pH-based system, offering a wide range of applications in drug delivery. The pH-sensitive coating of microsponges can respond to changes in pH by swelling or shrinking, thus releasing the active substance. This enables targeted drug delivery to specific areas of the body with diffrent pH levels, such as the stomach, skin, or intestines, providing numerous applications in drug delivery.

Method for preparing microsponges:

Microsponges can be prepared using various methods, but two common approaches are liquid-liquid suspension polymerization and quasi-emulsion solvent diffusion.

In liquid-liquid suspension polymerization, a polymer is dissolved in a water-immiscible organic solvent along with a cross-linking agent, and then a water-soluble monomer is added to create a water-in-oil emulsion. The emulsion is then polymerized, resulting in microsponges suspended in the organic solvent.¹⁹

In quasi-emulsion solvent diffusion, a water-soluble polymer and cross-linking agent are dissolved in an organic solvent, which is then added to an aqueous phase containing a surfactant. The two phases are stirred to create a quasi-emulsion, and the solvent is slowly diffused into the aqueous phase, resulting in the formation of microsponges.²⁰

Recently, new methods for microsponge preparation have been developed, such as supercritical fluid technology and electrospraying. Supercritical fluid technology involves the use of supercritical fluids to dissolve and expand a polymer, which is then rapidly depressurized to form microsponges. Electrospraying involves the use of an electric field to create microdroplets of a polymer solution, which are then solidified to form microsponges.

Each preparation method has its advantages and disadvantages, such as scalability, reproducibility, and complexity. The method used is determined by the formulation's requirements. and the intended application of the microsponge.

Other methods:

Water-in-oil emulsion solvent diffusion in water:

The water-in-oil emulsion solvent diffusion in water method involves dispersing an emulsifier-containing aqueous phase into an organic polymer solution. A water-in-oil emulsion is then formed and re-dispersed into an outer aqueous phase containing PVA to create a double emulsion. This technique is versatile and can incorporate drugs with varying solubilities, including both water-soluble and water-insoluble drugs²¹

Solvent diffusion in oil-in-oil emulsion:

This approach creates an emulsion because the interior phase contains a volatile organic liquid. In most preparations, dichloromethane is used as the volatile solvent. And the polymer used here is polylactide glycolic acid with a range of 85. With continuous stirring, the internal phase was added dropwise to the dispersing medium to obtain a microsponge.²²

Addition porogen:

The process described involves using a porogen, such as hydrogen peroxide or sodium bicarbonate, as the internal phase. This porogen is mixed with a polymer solution to create a uniform dispersion system, which is then added to an aqueous phase containing PVA. The addition of hydrogen peroxide leads to the formation of interconnected pores with a diameter of 5 to 20μm. This process results in the creation of microsponges with a porous structure, which can enhance skin absorption and drug delivery.²³

Lyophilization:

This method involves the conversion of microspheres into porous microspheres through the quick elimination of the solvent, leading to the creation of pores within the microspheres. Chitosan hydrochloride solution is used for this process. The microspheres are immersed in the solution and then subjected to lyophilization. However, this rapid solvent removal process may cause the microspheres to crack or shrink.²⁴

Vibrating orifice aerosol generator method (VOAG):

VOAG method is primarily intended for the preparation of lipid bilayer neutral silica particles. Core beads were prepared with tetraethylorthosilicates, ethanol, water and dilute hydrochloric acid were heated under reflux to prepare stock solutions. And this solution was diluted with solvent containing surfactant and further received single-disperse droplets. The microspheres formed are enclosed in lipomas.²⁵

Applications of microsponges:

Microsponges for Skin protection:

Microsponges can enhance the effectiveness of sunscreens by protecting against harmful UV rays. Researchers developed microsponges for topical administration of the broad-spectrum sunscreen agent Oxybenzone to address its skin irritation, dermatitis, and systemic absorption issues in lotion and cream forms. Through a semi-emulsion solvent diffusion technique, they optimized the use of ethyl cellulose and dichloromethane and dispersed it into a hydrogel for testing. The optimized microsponge gel demonstrated an entrapment efficiency of 96.9%, controlled release, high elasticity, and non-irritating properties. It also had a higher sun protection factor of 25 compared to the SPF of 20 in the marketed lotion, indicating prolonged oxybenzone retention.²⁶

Microsponges for psoriasis:

Psoriasis is a severe chronic inflammatory disease. As a result, the infected person's well-being suffers. Psoriasis-related microsponges have also been investigated. TheMometasonefuroatemicrosponges were created utilising the emulsion solvent diffusion process. Mometasone furoate is used to treat psoriasis and other inflammatory and irritating disorders. Microsponges were created using the emulsion solvent diffusion process. The release patterns indicated a two-phase release with an initial rapid release effect. The seven formulations had drug release rates of 29%-36% in the first hour and 78%-95% after 8 hours.^27,28,29,30

Microsponges for skin infections:

Gels and creams of microsponges are also used to treat a variety of skin infections, including eczema and dermatitis. Mupirocin is an antibiotic that is commonly used to treat skin infections caused by bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). However, frequent use of mupirocin can lead to the development of bacterial resistance. By incorporating mupirocin into microsponges, the drug can be delivered more effectively and efficiently, which may help to reduce the risk of resistance.

The study by Amrutiya and colleagues showed that mupirocinmicrosponges incorporated into an emulgel base could provide sustained drug delivery to the skin for up to 24hours. The results of the Draize patch test demonstrated that the microsponge formulations were stable and safe for use on the skin. The drug release from the microsponge gel was slower than that from the ointment, which could result in a more prolonged therapeutic effect.³¹

Microsponges for diabetic wound healing:

The use of nebivolol-loaded microsponges in a gel for wound healing is unique because it combines the benefits of a vasodilator medication with the controlled and sustained release properties of microsponges. Nebivolol, as a vasodilator, can help improve blood flow and restore endothelial function in diabetic wounds, which are known to have impaired healing due to reduced blood flow. By incorporating nebivolol into microsponges, the drug can be delivered slowly and steadily to the wound site, providing a prolonged therapeutic effect and promoting faster healing. Moist wound healing has been shown to be beneficial for wound closure as it can improve cellular migration and proliferation, reduce inflammation, and promote angiogenesis. By incorporating nebivolol-loaded microsponges into a gel, a sufficient moist wound management environment can be provided, which can help to enhance the healing process.

The in vitro studies demonstrating 80% drug release within 8 hours and the rapid and significant wound healing and closure in diabetic rats with the microsponge gel further highlights the potential of this approach for wound healing. The controlled and sustained release properties of microsponges can help to ensure that the drug is available at the wound site for an extended period, which can contribute to faster and more efficient wound healing.³²

Microsponges for Fungal infections:

Fungal infections are a global health concern and are treated with topical antifungal agents, but these formulations have drawbacks. Microsponges can address these limitations by enhancing drug penetration, reducing irritation, and sustaining drug release. They are an emerging drug delivery system with potential in improving topical antifungal therapy.

Terbinafine hydrochloride is antifungal drug is entrapped in microsponges using a quasi-emulsion solvent diffusion technique for controlled release of the drug, with the goal of avoiding side effects. The formulations were analyzed for physical characteristics and in vitro release, and the most effective formulation was incorporated into gels using carbopol. The best-performing gel had a pH of 6.2, viscosity of 3960 cps, and drug content of 87.6%, with in vitro release following a fickian pattern. Antifungal studies showed comparable results to the marketed formulation, with better antifungal activity on fungal-induced guinea pig skin. Microsponge gel show minimize side effects and decreased the frequency of gel usage for fungal treatment.³³

Srilakshami and Prathima's use of microsponges loaded with voriconazole, encapsulated with Eudragit RS100 and L100, presents a promising option for treating fungal infections. The microsponges, synthesized using a quasi-emulsion diffusion method, exhibit high encapsulation efficiency. In vivo studies on guinea pigs infected with Candida albicans reveal significant antimicrobial and antifungal activity, outperforming conventional fluconazole gel. Additionally, the microsponge loaded voriconazole gel demonstrated a greater zone of inhibition in antimicrobial studies compared to the commercial fluconazole gel used as a control. This research highlights the potential of voriconazolemicrosponge loaded gel in treating fungal infections.³⁴

Microsponges for Acne:

Acne vulgaris is a prevalent skin condition that impacts almost 80% of teenagers and young adults. It is caused by the obstruction and inflammation of sebaceous glands and hair follicles, resulting in the formation of comedones, papules, pustules, and nodules. Current treatment options for acne include topical and oral medications, such as antibiotics, retinoids, and benzoyl peroxide. However, these treatments often have limitations, such as poor patient compliance, skin irritation, and bacterial resistance.³⁵

Microsponges are a promising drug delivery system for the treatment of acne, due to their ability to encapsulate and release anti-acne agents in a controlled manner, reducing skin irritation and improving patient compliance. Microsponges are porous polymeric particles that can absorb and retain large amounts of drugs, and can be formulated into topical gels, lotions, and creams.^36,37

One study investigated the use of microsponge technology for the delivery of benzoyl peroxide, a widely used anti-acne agent that can cause skin dryness, irritation, and erythema. The authors prepared benzoyl peroxide-loaded microsponges using a solvent evaporation method and evaluated their physical properties, drug release behavior, and anti-acne efficacy. They found that the microsponges had a high drug loading capacity, sustained release pattern, and improved stability compared to conventional benzoyl peroxide formulations. Moreover, the microsponge gel showed a greater reduction in acne lesions and skin irritation in vivo than the commercial benzoyl peroxide gel.^36,37

Microsponges for Atopic Dermatitis:

Dermatitis is a common skin condition characterized by inflammation, redness, and itchiness. It causes by a variety of factors, like allergies, irritants, genetics, and infections, and can be treated with topical medications.³⁵

Microsponge gel containing naringenin for the treatment of atopic dermatitis were prepared using ethyl cellulose and optimized using a 32-factorial design. The optimized microsponge was incorporated into Carbopol gel to create a 1% naringenin-containing Microsponge gel. The effectiveness of the Microsponge gel was compared to a plain naringenin gel in albino Wistar rats. The results showed that the Microsponge gel had a particle size of 180 μm, 92.3% ±2.37 in vitro drug release, and achieved 82% entrapment. The Microsponge gel also showed faster healing, reduced earflap thickness, and lower WBC counts compared to the plain gel. Additionally, the Microsponge gel had a three-fold greater drug deposition in the skin. Therefore, the naringenin-loaded microsponge gel may be a promising natural treatment for atopic dermatitis.³⁸

The use of miconazole nitrate-loaded microsponges for diaper dermatitis treatment. Preparation using a 2³ factorial design and the emulsion solvent diffusion technique, the independent variables' effects on encapsulation efficiency, particle size, surface topography, and in vitro drug release were evaluated. A gel was prepared using the optimized formulation and assessed for pH, viscosity, spreadability, in vitro drug diffusion, in vitro antifungal effects, and stability. The results showed that the miconazole nitrate-loaded microspongegel is a promising alternative to traditional treatments for diaper dermatitis due to its uniform particle size, spherical shape, porous nature, and controlled release of the drug. This formulation provides a reliable and economical cure for diaper dermatitis.³⁹

Microsponges for Hyperpigmentation:

Hyperpigmentation is a skin disorder caused by the overproduction of melanin, resulting in dark spots or patches. Developing safe and effective topical treatments for hyperpigmentation is crucial in dermatology. Microsponges can provide a viable option by releasing drugs in a controlled and sustained manner, while minimizing side effects on skin.

Deshmukh et al. formulated glabridinmicrosponge using ethyl cellulose as the polymer for effective management of hyperpigmentation disorder. Microsponges were evaluated for particle size, drug concentration, thermal stability, and porosity parameters using mercury intrusion porosimetry. Later, microsponges were added to a gel formulation for use as a topical application. The gel's skin whitening effect was assessed in guinea pigs using UV B radiation to induce hyperpigmentation. Histopathological evaluation of the animals' skin after treatment showed effective reduction in melanin density. The new formulation has potential for use in the cosmetics industry as a skin whitening agent.⁴⁰

Microsponges for skin cancer:

A gel containing 5-FU was developed using microsponge technology to treat skin cancer. The microsponge formulation showed better surface area and pore volume than the commercial cream, and had improved texture properties. In an in-vivo study, the optimized formulation resulted in a 5.5-fold increase in skin deposition and less skin irritation compared to the commercial cream. Hence, the microsponge-based formulation could be a potential alternative for skin cancer treatment.^41,42

Microsponges for Herpes:

Acyclovir and its analogues are approved antiviral drugs for treating herpes simplex virus (HSV) by inhibiting viral DNA replication, with a low risk of adverse effects.⁴³

Researcher develop an acyclovir-loaded microsponge-based emulgel, the study aimed to boost the skin penetration of acyclovir from traditional topical formulations.The optimal batch was created with a homogenization speed of 1000 rpm, a drug to polymer ratio of 1.6, and a PVA content of 0.088%.The improved microsponge-loaded emulgel's viscosity, spreadability, pH, and drug concentration were all appropriate.Results from an ex vivo permeation research showed that the modified microsponge-loaded emulgel significantly improved drug penetration compared to the commercial formulation. The findings suggest that the developed microsponge-based emulgel may be a promising approach to enhance the topical delivery of acyclovir.⁴⁴

CONCLUSIONS:

Microsponge-based delivery systems offer enhanced therapeutic performance for active molecules in cosmetic and dermal applications. They increase permeation while reducing transdermal penetration, extend drug residence in skin, and allow for prolonged drug release. This technology has promising potential for a new generation of dermatological and cosmetic treatments. Microsponge technology is an important tool for both scientific research and the commercialization of innovative dermatological solutions. Microsponges can be used as carriers for actives, providing controlled release and improving therapeutic delivery. They also overcome the problem of local irritation associated with certain drugs. Microsponges are too large to be absorbed through the skin, making them safe for use. However, there are still some unexplored areas about their biocompatibility and toxicity, which calls for further studies. The use of microsponge-based cosmetic anddermatological products is likely to increase in the near future.

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Received on 10.05.2023 Modified on 18.12.2023

Research J. Topical and Cosmetic Sci. 2024; 15(1):6-12.

DOI: 10.52711/2321-5844.2024.00002