Polymers from renewable resources: Drug delivery platforms for transdermal delivery

Introduction

The skin is a crucial protective organ with a specialized barrier system that tightly regulates transport of substances into the body. The stratum corneum poses a major obstacle for transdermal drug delivery.^1–3 Recently, there has been increasing interest in using polymers from renewable resources to engineer nanoscale drug delivery systems. Polymers derived from natural sources such as cellulose, starch, and chitosan have emerged as promising platforms due to their biocompatibility, biodegradability, and versatility in nanocarrier design. Several features make polymers from renewable resources well-suited as nanoscale transdermal drug delivery systems. First, their small size distribution enables passive penetration through tight junctions in the stratum corneum.^4,5 Second, renewable polymer nanoparticles can be functionalized for targeting specific cells and receptors. ⁶ Third, they provide spatiotemporal control over drug release kinetics across the skin layers. ⁷ Modification of size, shape, surface chemistry, and ligand conjugation further facilitates interaction and transport across the stratum corneum. ⁸ Third, multifunctional nanoscale platforms provide spatiotemporal control over drug release and target delivery. ⁹ Modification of size, shape, surface chemistry, and inclusion of targeting moieties on nanocarriers further facilitates interaction and transport across barrier cells and tissues. Taken together, these advantages have driven extensive research on nanomedicines for non-invasive and efficient drug delivery to the skin, and eyes.^8–11

This letter highlights recent progress in renewable polymer-based nanotechnology platforms focused on breaching the dermal barrier. We examine the skin as a major biological barrier where renewable nanocarriers have demonstrated enhanced permeation and therapeutic efficacy. For the dermal barrier, we discuss disease contexts, specific nanoparticle platforms under development, and address translational considerations towards clinical application. Overall, this review provides current knowledge on leveraging renewable polymer nanoscale design to overcome the restrictive stratum corneum for targeted transdermal therapy.

In recent decades, particular attention has been paid to polymers from renewable resources and they are known as promising nanocarriers in the cosmetics industry because of the researchers interest in specific physicochemical properties of these nanocarriers—high bioavailability, low toxicity, biocompatibility, biodegradability and their encapsulation with high efficiency. ¹² They can be quickly removed (opsonization) from the blood stream and their surface modification can be easily accomplished by coating them with an appropriate polymer. ¹³ Moreover, because of biobased renewable polymers’ similarity to the cell membrane structure, they are ideal nanocarriers for the purpose of targeting drugs into the skin. However, biobased renewable polymer-based delivery systems have some limitations when it comes to skin. These limitations include problems with the penetration of biobased renewable polymers into the skin, their elimination over time, and reducing their stability. ¹⁴ Conventional biobased renewable polymers tend to remain in the outermost layers of the skin and do not reach the target sites in the deeper layers, and so they are being used for local dermal drug delivery.^15,16 However, by reducing their size and applying surface modifications, it is possible to yield nanobiopolymers capable of penetrating through the deeper layers of skin. In general, nanocarriers up to 200 nm can penetrate easily and conveniently . ¹⁴ Researchers have shown that using a polymer layer to coat the biobased renewable polymers such as algenin, peptide, chitoson, pectin, or a silica layer not only increases biobased renewable polymer surface charge charge towards positive but also prevents lipid oxidation and encapsulated compounds leakage.^17–19

In this Regard, Polysaccharides have been extensively studied in the field of drug delivery systems due to their biocompatibility, ability to degrade naturally, and low toxicity. ²⁰ They are also used in the production of microneedles. ²¹ Different polymers are used in transdermal drug delivery because of their unique physical and chemical properties, controllability, and drug release mechanisms. Polysaccharides derived from natural sources like plants, animals, and microorganisms are widely used in this context. This is mainly because they are biocompatible, can degrade naturally, are easy to make, and provide sustainable delivery. Among the polysaccharides, hyaluronic acid (HA), dextran, chitosan (CS), cellulose, sodium alginate (SA), and blends of other biopolymers have been extensively studied. A summary of the polysaccharides used for microneedling can be found in Table 1.

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Table 1.

Utilization of natural polysaccharides in microneedling procedures.

Name	Structure	Property	Ref
Hyaluronic acid		• Water-soluble	22,23
		• Handle large medication quantities
		• Enhance distribution
		• Accelerating initiation of effects
Cellulose		• Water-insoluble	24
		• Film former polymers
Chitosan		• Antibacterial	25
		• Wound healing
		• Poor mechanical strength
Alginate		• High mechanical strength	26

Besides nanosized particles, drug delivery via microarray patches has emerged as a preferred route for many bioactive compounds compared to traditional injection methods (Figure 1). ²⁷ Extensive research has focused on developing microneedles patches using materials like silicon, metals, and polymers. Polymeric microarray patches are especially attractive due to advantages including high drug loading, biocompatibility, lack of toxicity, biodegradability, and inexpensive fabrication.^28,29 Polymeric microneedles (MNs) can be designed as dissolvable, solid, swellable, or composite platforms. Dissolvable MNs dissolve rapidly in skin after insertion to release drugs without leaving sharp residues. However, dissolvable polymers often have poor mechanical properties, limiting polymer options that combine suitable biocompatibility, strength, and dissolution rate.^30,31

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Figure 1.

A comparison between various transdermal drug delivery systems.

In summary, nanoscale and microscale platforms have shown promise for transdermal drug delivery by overcoming the barrier posed by skin. Engineered nanocarriers such as solid lipid nanoparticles, polymeric micelles, and dendrimers enable controlled permeation and release into the dermal layers. Surface functionalization and size reduction of nanoparticles facilitate passive and active transport across the stratum corneum. Renewable polymer nanoparticles and microneedle arrays represent biocompatible transdermal delivery platforms.

Future research should focus on optimizing nanocarrier and microneedle design for stability, biocompatibility, and minimal side effects. Continued development of nanotechnology solutions will be key for precisely breaching the skin’s barrier and improving transdermal delivery. Advances in areas like antioxidant delivery, gene therapy, and leveraging active transport warrant investigation. Overall, nanomedicines and microneedles have potential to enhance transdermal treatment by increasing permeability, specificity, and efficacy while reducing risks. Further engineering of clinically viable nanoformulations and microneedle platforms remains crucial for non-invasive delivery across the dermal barrier.